Polycystic kidney disease (PKD) is usually an inherited condition. It belongs to a group of diseases known as cystic kidney disease.

Faulty genes cause abnormal blisters of fluid (cysts) to grow in the kidneys. Both kidneys are usually affected but one may develop the cysts earlier than the other. The cysts continue to grow until they compress the healthy tissue and stop the kidneys from working properly. The kidneys get larger along with the cysts, which can number in the thousands. Polycystic kidney disease is a common cause of kidney failure in Australia and equally affects men and women of different ethnic backgrounds. Men usually progress faster to kidney disease, although it is unclear why this occurs. There is currently no cure but the disease can be managed and research into treatment options is ongoing. The two major inherited forms of polycystic kidney disease are: Autosomal dominant PKD

Autosomal recessive PKD.

Autosomal dominant PKD

This is the most common inherited form of polycystic kidney disease. A parent with autosomal dominant PKD has a 50 per cent chance of passing the faulty gene and associated disease to each of their children. If a person doesnt inherit the gene, there is no chance of their children inheriting the gene because it never skips a generation. Occasionally, a person develops the disease when there is no family history. It is thought that a different inheritance pattern or perhaps a genetic mutation may be responsible. Like inherited PKD, the affected person has a 50 per cent chance of passing the faulty gene and associated disease to each of their children. Autosomal dominant PKD can lead to kidney failure.

Symptoms of autosomal dominant PKD

There may be no symptoms in the early stages. The cysts usually start growing during the teenage years. As the cysts replace healthy tissue, the outline of the kidneys looks irregular or moth -eaten. Symptoms and signs usually develop between the ages of 30 and 40 (but can begin earlier), and may include: High blood pressure (may occur before cysts appear)

Pain in the back or sides Headaches Enlarged and painful abdomen Blood in the urine (haematuria) Urinary tract infections Kidney stones Liver and pancreatic cysts Abnormal heart valves Aneurysms in the brain Diverticulosis (the development of abnormal pouches in the walls of the large intestine) Abdominal wall hernias.

Autosomal recessive PKD

This is a less common inherited form of polycystic kidney disease. Signs begin in the early months of life or even while the baby is still developing in the uterus (womb). Autosomal recessive PKD is sometimes called infantile PKD. Children born with autosomal recessive PKD often develop kidney failure within a few years of birth and experience liver problems as they grow into adults.

Symptoms of autosomal recessive PKD

Symptoms and signs in severely affected babies can include: Reduced amniotic fluid surrounding the baby in the uterus An unusual shape to the face due to the lack of amniotic fluid (Potter facies)

Enlargement of the childs abdomen due to enlarged kidneys, liver or spleen Heart defects Underdeveloped lungs Kidney failure at birth or in the first few weeks of life.

Diagnosis of polycystic kidney disease

The severe symptoms of autosomal recessive PKD usually result in a prompt diagnosis. However, in most cases of autosomal dominant PKD, a persons physical condition can appear normal for many years. Physical check -ups or blood and urine tests may not always identify the disease. It is often detected during medical investigations for other health problems, such as urinary tract infections. At other times, the disease isnt discovered until the kidneys fail. Diagnosis of PKD may involve a number of tests including: Physical examination can detect symptoms such as high blood pressure or enlarged kidneys.

Blood tests to assess kidney function. Urinalysis blood or protein (or both) may be found in the urine. Ultrasound a simple, non-invasive test that can identify even quite small cysts. Computed tomography (CT) and magnetic resonance (MRI) scans these may be required if the results from the ultrasound are inconclusive or if more information is needed. These techniques can detect very small cysts. Genetic testing this is not a routine test but may be used for family testing. The presence of the abnormal genetic material can be detected with special blood tests. Genetic counselling is available for affected couples.

Treatment of polycystic kidney disease

There is no cure for PKD. However, regular monitoring of the kidneys and treatment for the associated complications can help to maintain health and prolong a persons lifespan. Common complications and their treatments include: Trauma consider avoiding contact sports if your kidneys, liver, spleen or abdomen are enlarged. A strong blow to the belly could injure affected organs.

High blood pressure controlling high blood pressure is very important. Antihypertensive medications may be prescribed. Blood in the urine fluids, analgesics, antibiotics and bed rest may be recommended. Urinary tract infections symptoms may include frequency to urinate, painful urination and fever. Consult with your doctor immediately about treatment with antibiotics. An untreated urinary tract infection can spread to the kidneys. Kidney failure this is treated by dialysis, which is a procedure to remove waste products and extra water from the body by filtering the blood through a special membrane. A kidney transplant is another treatment option. PKD does not redevelop in the transplanted kidney.

Liver cysts these do not usually affect liver function. Non-surgical management may include avoiding hormone replacement therapy (HRT), also known as hormone therapy (HT). Surgery may occasionally be needed to drain cysts or remove diseased parts of the liver. Rarely, a liver transplant is needed.

Clinical trials have begun in Australia to test medication that alters the production of fluid by the kidney and appears to slow down cyst formation.

Self-care suggestions for polycystic kidney disease

Be guided by your doctor but self-care suggestions may generally include: Changing your diet this may help to manage some symptoms. Dietary changes may include reducing salt, protein, cholesterol (fats) and caffeine. Dietary changes should be made only after discussion with your doctor or dietitian and will depend on your test results.

Making healthier lifestyle choices for example, participate in regular and moderate physical activity and maintain an appropriate weight for your height and build. Not smoking is strongly advised.

Avoiding non-steroidal anti-inflammatory medications (NSAIDs) these should not be taken without medical advice as they can worsen kidney function. Your doctor will give you detailed instructions on how to best take care of yourself. Follow these instructions carefully.

Where to get help

Your doctor Kidney Health Australia Information Line Tel. 1800 4 KIDNEY (543 639), TTY users phone 1800 555 677 then ask for 1800 454 363 The National Renal Resource Centre Tel. (02) 9362 3995 or 1800 257 189 The Polycystic Kidney Disease Association based at the National Renal Resource Centre.

Things to remember
Polycystic kidney disease (PKD) is an inherited condition characterised by the growth of cysts on the kidneys. The disease may have no symptoms until it is well advanced. There is currently no cure for PKD but treatment can reduce or prevent complications and prolong the persons lifespan.

Proteinuria is often diagnosed incidentally on routine dipstick testing of urine samples. At other times, appropriate indices of suspicion are required to specifically request urinalysis for protein measurement. It is important to distinguish benign, self-limiting aetiologies from more significant illness. Although the list of differential diagnoses for proteinuria includes almost all aetiologies of kidney disease, it is useful to consider several principles when assessing proteinuria. In general, diseases that affect pre-glomerular structures (e.g., medium-vessel vasculitis, heart failure), macroscopic structural abnormalities (e.g., cystic kidney disease, urinary tract obstruction), lower urinary tract infection, ischaemia, and medication toxicity often result in minimal to low-grade proteinuria. More significant aetiologies of proteinuria typically include glomerular diseases and plasma cell dyscrasias. The presence

of haematuria with overt proteinuria suggests nephritis. Although exceptions do exist, it is helpful to work within this framework. Proteinuria itself typically has few signs or symptoms. Nephrotic-range proteinuria may, on occasion, result in foamy urine, although normal rates of protein excretion can also produce foam if the urine is highly concentrated. Oedema may be present, and with severe ongoing proteinuria, malnutrition, weight loss, and infection may result. Nephroticrange proteinuria may result in pleural effusions and ascites, with resultant shortness of breath and abdominal distention.

Historical factors
Transient proteinuria (from fever, heavy physical exertion, urinary tract infection, urological haemorrhage, orthostatic proteinuria) may present with transient symptoms.

These include fever, recent strenuous exercise, dysuria, urgency, frequency, offensive smelling/cloudy urine, and/or trauma.

Age may be an important historical factor.

Presentation of proteinuria in children/adolescents is commonly due to orthostatic proteinuria and minimal change disease. Minimal change disease and membranous nephropathy is also common in older patients.

Ethnicity can also be an important historical factor.

Focal segmental glomerulosclerosis is more common in black people. There is a high incidence of IgA nephropathy in Asians. Balkan endemic nephropathy is endemic to residents of Balkan territories.

Symptoms of persistent proteinuria vary according to the cause.

Swelling may be a symptom of minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, systemic lupus erythematosus (SLE), postinfectious glomerulonephritis, amyloidosis, light and heavy chain deposition diseases, fibrillary and immunotactoid glomerulopathy, light chain cast nephropathy, haemolytic uraemic syndrome (HUS), or thrombotic thrombocytopenic purpura (TTP).

Patients with IgA nephropathy, anti-glomerular basement membrane (anti-GBM) disease (Goodpasture's syndrome), cystic kidney disease, or Balkan endemic nephropathy may describe gross haematuria. Pain may be a symptom of cystic kidney disease, urinary tract obstruction, medium- and small-vessel vasculitis, heavy metal poisoning, and rhabdomyolysis. Patients with Fabry's disease may have a burning sensation of the hands with exercise and heat.

Altered bowel habit may be a symptom of hypercalciuria (constipation) and HUS (diarrhoea).

Seizures may be symptoms of TTP and SLE. Polyuria may be a symptom of hypercalciuria, Dent's disease, and urinary tract obstruction. Ocular symptoms may be present in patients with Fabry's disease, diabetic nephropathy, hypertension, and cystic kidney disease. Respiratory symptoms may be associated with medium- and small-vessel vasculitis, IgA nephropathy, and sclerodermal renal crisis.

Past medical history can reveal useful information.

Lymphoma and stem cell transplant may be associated with minimal change disease. HIV, hypertension, diabetes, prior renal injury, and obesity may be associated with focal segmental glomerulosclerosis. SLE, hepatitis B, hepatitis C, syphilis, and stem cell transplant may be associated with membranous nephropathy. SLE, hepatitis C, post-infectious glomerulonephritis, endocarditis, cryoglobulinaemia, and thrombotic microangiopathy may be associated with membranoproliferative glomerulonephritis. Upper respiratory infection, Crohn's disease, or coeliac disease may be associated with IgA nephropathy. Autoimmune disease with rash, photosensitivity, oral ulcers, arthritis, serositis, renal disease, neurological changes, and haematological disease may be associated with SLE. Recent infection (typically streptococcal, can be staphylococcal) may be associated with post-infectious glomerulonephritis. Arthritis, familial Mediterranean fever, multiple myeloma, or monoclonal gammopathy may be associated with amyloidosis. Multiple myeloma and monoclonal gammopathy may also be associated with light and heavy chain deposition diseases. Multiple myeloma, monoclonal gammopathy, hepatitis C, and lymphoma may be associated with fibrillary and immunotactoid glomerulopathy. Rapidly progressive renal failure may be associated with anti-GBM disease (Goodpasture's syndrome). Recent nephrotoxic injury such as hypotension, mechanical ventilation, and ischaemia may be associated with acute tubular injury. Uveitis from tubulointerstitial nephritis and uveitis syndrome, viral infection, and systemic disease (e.g., sarcoidosis, Sjogren's disease) may be associated with interstitial nephritis. Multiple myeloma may be associated with Fanconi syndrome. Kidney stones may be associated with hypercalciuria. Chronic kidney disease, rickets, and nephrocalcinosis may be associated with Dent's disease. Anaemia and chronic kidney disease between the ages of 30 and 50 years may be associated with Balkan endemic nephropathy. Multiple myeloma, monoclonal gammopathy, and rapid-onset renal failure may be associated with light chain cast nephropathy.

Benign prostatic hyperplasia, kidney stones, urinary retention, and gynaecological cancer may be associated with urinary tract obstruction. Cerebral haemorrhage, stroke, and childhood nephronophthisis may be associated with cystic kidney disease. Insulin resistance/diabetes, dyslipidaemia, and obesity may be associated with metabolic syndrome. Diabetes and retinopathy is associated with diabetic nephropathy. Eye disease, peripheral and coronary arterial disease, congestive heart failure, hypohidrosis, gastrointestinal dysmotility, and renal failure may be associated with Fabry's disease. Recent Escherichia coli infection, diarrhoea, prior history of HUS/TTP, and prior bone marrow transplant may be associated with HUS/TTP. Pregnancy or post-partum state may be associated with HUS. Scleroderma is associated with sclerodermal renal crisis. Multi-organ disorder, neuropathy, headache, cerebrovascular accident, and acute renal failure may be associated with medium- and small-vessel vasculitis. Recent crush injury, prolonged immobility, or viral infection may be associated with rhabdomyolysis.

Family history may be positive for the following diseases.

HUS/TTP. Fanconi syndrome. Dent's disease.

Occupational/social history may be relevant.

Industrial/environmental exposures to old paint and moonshine are common sources for heavy metal (lead) poisoning. Patients with anti-GBM disease (Goodpasture's syndrome) often have positive smoking histories.

Drug history may also reveal important information.

Non-steroidal anti-inflammatory drugs (NSAIDs), interferon, and lithium may be associated with minimal change disease. Bisphosphonates and heroin use may be associated with focal segmental glomerulosclerosis. NSAIDs, gold, and penicillamine may be associated with membranous nephropathy. NSAIDs, aminoglycosides, amphotericin B, zoledronic acid, oral phosphate bowel preparations, and IV contrast may be associated with acute tubular injury. NSAIDs, antibiotics, allopurinol, and proton pump inhibitors may be associated with interstitial nephritis. Heavy metal exposure and medications such as tenofovir may be associated with Fanconi syndrome. Aristolochic acid and other weight loss medications may be associated with aristolochic acid nephropathy (previously called Chinese herb nephropathy). Aristolochic acid weight loss medications may also be associated with tubulointerstitial disease.

Ciclosporin, clopidogrel, gemcitabine, and bevacizumab (vascular endothelial growth factor inhibitor) may be associated with HUS or TTP.

Prednisone may be associated with scleroderma renal crisis. Statins and cocaine may be associated with rhabdomyolysis.

Physical examination
Signs of transient proteinuria (from fever, heavy physical exertion, urinary tract infection, urological haemorrhage, orthostatic proteinuria) are transient.

They may include elevated temperature >38.0C (100.4F), flank pain (if pyelonephritis), bladder tenderness on palpation, and/or gross haematuria. There are no specific findings for heavy physical exertion or orthostatic proteinuria.

Signs of persistent proteinuria vary according to the cause.

Fever may be a sign of interstitial nephritis, Fabry's disease, HUS, or TTP. Oedema (in the form of pleural effusion, ascites, or peripheral oedema) may be a sign of minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, SLE, post-infectious glomerulonephritis, amyloidosis, light and heavy chain deposition diseases, fibrillary and immunotactoid glomerulopathy, light chain cast nephropathy, HUS, or TTP.

Hypertension itself may cause proteinuria or may be a sign of other causes, including HUS, TTP, scleroderma renal crisis, glomerular disease, IgA nephropathy, SLE, post-infectious glomerulonephritis, amyloidosis, light and heavy chain deposition disease, fibrillary and immunotactoid glomerulopathy, light chain cast nephropathy, metabolic syndrome, and Fabry's disease.

Neurological weakness may be a sign of hypercalciuria, heavy metal poisoning, SLE, diabetic neuropathy, or medium- and small-vessel vasculitis. Altered mental status may be a sign of hypercalciuria, TTP, medium- and small-vessel vasculitis, heavy metal poisoning, or SLE. High BMI may be a sign of metabolic syndrome, Fabry's disease, or focal segmental glomerulosclerosis. Rash may be a sign of membranoproliferative glomerulonephritis, glomerular disease, interstitial nephritis, HUS, TTP, medium- and small-vessel vasculitis, heavy metal poisoning, Fanconi syndrome, or SLE.

Who to test

Patients with acute or chronic kidney disease. [3] [26] Patients with hypertension require screening for microalbuminuria at diagnosis and then annually in high-risk groups (e.g., diabetes mellitus, reduced kidney function). [27] Patients with type 1 diabetes mellitus require annual screening for microalbuminuria 5 years after diagnosis, and patients with type 2 diabetes mellitus require screening at time of diagnosis. [28] Patients with metabolic syndrome. As part of the assessment of patients with oedema, haematuria, or systemic disease (e.g., cirrhosis, HIV infection, vasculitis).

Routine testing of the general population is not recommended by professional societies.

How to test
It is important to distinguish persistent and transient proteinuria. The presence of dipstick-positive proteinuria on 2 urine samples separated by 1 to 2 weeks indicates persistent proteinuria and warrants quantification and further assessment. [3] It is important to have a high index of suspicion for persistent proteinuria. For example, although urinary tract infection is a common cause of transient haematuria and mild (1+) proteinuria, it is important to at least consider more serious aetiologies of these urinary abnormalities whenever they are encountered. Follow-up testing is important if the clinical situation warrants it. If orthostatic proteinuria is suspected, the protein-tocreatinine ratio in a first morning voided urine specimen should be compared with the ratio from a random sample later in the day. The absence of proteinuria in the morning sample and presence in the daytime sample confirms orthostatic proteinuria. Although qualitative dipstick testing is still widely used, a negative dipstick does not exclude the presence of proteinuria. Screening for microalbuminuria may be more sensitive for the detection of early glomerular disease than measuring total protein excretion, but either method may be used. Semi-quantitative testing (or preferably direct measurement of a spot or 24-hour urine sample) for calculation of a protein-to-creatinine ratio is recommended. Spot urine from a first morning void is preferred, but an untimed urine sample is acceptable. The use of quantitative methods is particularly important when concern for non-albumin proteins (e.g., light chains in multiple myeloma) exists. Although qualitative methods may be used for the initial detection of proteinuria, quantitative methods should be used for confirmation and ongoing follow-up. [3]

Further tests
The presence of persistent proteinuria should prompt assessment of kidney function by estimation of glomerular filtration rate (GFR) from serum creatinine and/or collection of 24-hour urine for creatinine clearance. GFR can be estimated by the Modification of Diet in Renal Disease (MDRD) equation or by creatinine clearance derived from the

Cockcroft-Gault equation. In patients with a GFR >60 mL/minute/1.73 m^2, the MDRD equation may underestimate true kidney function. For these patients, 24-hour urine collection for measurement of creatinine clearance may be more accurate. In patients with overt proteinuria, renal imaging by ultrasound or a similarly appropriate modality should be obtained. The work-up of proteinuria is similar for glomerular, tubular, and overflow proteinuria. Further laboratory assessment is directed by the results of a comprehensive history and physical examination. Unless the clinical history overwhelmingly supports tubular proteinuria, glomerular proteinuria typically is assessed first. In instances of tubular or overflow proteinuria, these diagnoses are often rendered in the course of routine assessment. Further testing for microalbuminuria includes:

Lipid profile for assessment of metabolic risk factors Haemoglobin A1c for assessment of diabetes mellitus Clinical assessment and possibly echocardiography for heart failure Measurement of blood pressure.

Further testing for overt proteinuria includes:

Reviewing medication list for potentially offending agents Full blood count with differential to screen for haematological disorders Urinalysis with microscopic examination to assess for glucosuria, haematuria, and pyuria HIV testing if there is clinical suspicion of HIV Hepatitis B and C testing if there is clinical suspicion of infection Antinuclear antibody if there is clinical suspicion of autoimmune disease such as SLE Double-stranded DNA antibody if there is clinical suspicion of SLE CH50, C3, and C4 if there is clinical suspicion of SLE, post-infectious glomerulonephritis, cryoglobulinaemia/hepatitis C, or membranoproliferative glomerulonephritis Antineutrophil cytoplasmic antibody if there is clinical suspicion of pauci-immune vasculitis Serum and urine protein electrophoresis with immunofixation/serum-free light chain measurement if there is clinical suspicion of a plasma cell dyscrasia Rheumatoid factor if there is clinical suspicion of cryoglobulinaemia/hepatitis C Cryoglobulins if there is clinical suspicion of hepatitis C or cryoglobulinaemic vasculitis Anti-GBM antibody if there is clinical suspicion of anti-GBM disease or Goodpasture's syndrome Renal biopsy may be required in most cases for prognostic and therapeutic decision making and to secure a diagnosis if one is not readily apparent from history and serological testing.

Additionally, if predominately tubular proteinuria is suspected from clinical history or initial work-up, the following tests may be of value:

Heavy metal screening for the assessment of heavy metal poisoning Assessment for glucosuria, phosphaturia, and renal tubular acidosis for the assessment of Fanconi syndrome (if all 3 present in the setting of tubular proteinuria) Urinary albumin/beta-2-microglobulin ratio of approximately 1:13 (consistent with tubular proteinuria).

The frequency of follow-up protein measurement varies based on the clinical scenario. Formal guidelines recommend yearly measurement in patients with diabetes mellitus and high-risk patients with hypertension. Although specific recommendations do not exist for patients with abnormal renal function, in general, patients are typically reassessed and protein excretion remeasured 3 to 4 times per year. A particular patient may require more or less frequent monitoring depending on their circumstances

What is proteinuria?
Proteinuria-also called albuminuria or urine albumin-is a condition in which urine contains an abnormal amount of protein. Albumin is the main protein in the blood. Proteins are the building blocks for all body parts, including muscles, bones, hair, and nails. Proteins in the blood also perform a number of important functions. They protect the body from infection, help blood clot, and keep the right amount of fluid circulating throughout the body. As blood passes through healthy kidneys, they filter out the waste products and leave in the things the body needs, like albumin and other proteins. Most proteins are too big to pass through the kidneys' filters into the urine. However, proteins from the blood can leak into the urine when the filters of the kidney, called glomeruli, are damaged. Proteinuria is a sign of chronic kidney disease (CKD), which can result from diabetes, high blood pressure, and diseases that cause inflammation in the kidneys. For this reason, testing for albumin in the urine is part of a routine medical assessment for everyone. Kidney disease is sometimes called renal disease. If CKD progresses, it can lead to end-stage renal disease (ESRD), when the kidneys fail completely. A person with ESRD must receive a kidney transplant or regular blood-cleansing treatments called dialysis. [Top]

Who is at risk for proteinuria?

People with diabetes, hypertension, or certain family backgrounds are at risk for proteinuria. In the United 1 States, diabetes is the leading cause of ESRD. In both type 1 and type 2 diabetes, albumin in the urine is one of the first signs of deteriorating kidney function. As kidney function declines, the amount of albumin in the urine increases.

Another risk factor for developing proteinuria is hypertension, or high blood pressure. Proteinuria in a person with high blood pressure is an indicator of declining kidney function. If the hypertension is not controlled, the person can progress to full kidney failure. African Americans are more likely than Caucasians to have high blood pressure and to develop kidney problems from it, even when their blood pressure is only mildly elevated. In fact, African Americans are 2 six times more likely than Caucasians to develop hypertension-related kidney failure. Other groups at risk for proteinuria are American Indians, Hispanics/Latinos, Pacific Islander Americans, older adults, and overweight people. These at-risk groups and people who have a family history of kidney disease should have their urine tested regularly. 1 United States Renal Data System. USRDS 2007 Annual Data Report. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services; 2007. 2 Ibid. [Top]

What are the signs and symptoms of proteinuria?

Proteinuria has no signs or symptoms in the early stages. Large amounts of protein in the urine may cause it to look foamy in the toilet. Also, because protein has left the body, the blood can no longer soak up enough fluid, so swelling in the hands, feet, abdomen, or face may occur. This swelling is called edema. These are signs of large protein loss and indicate that kidney disease has progressed. Laboratory testing is the only way to find out whether protein is in a persons urine before extensive kidney damage occurs. Several health organizations recommend regular urine checks for people at risk for CKD. A 1996 study sponsored by the National Institutes of Health determined that proteinuria is the best predictor of progressive kidney failure in people with type 2 diabetes. The American Diabetes Association recommends regular urine testing for proteinuria for people with type 1 or type 2 diabetes. The National Kidney Foundation recommends that routine checkups include testing for excess protein in the urine, especially for people in high-risk groups. [Top]

What are the tests for proteinuria?

Until recently, an accurate protein measurement required a 24-hour urine collection. In a 24-hour collection, the patient urinates into a container, which is kept refrigerated between trips to the bathroom. The patient is instructed to begin collecting urine after the first trip to the bathroom in the morning. Every drop of urine for the rest of the day is to be collected in the container. The next morning, the patient adds the first urination after waking and the collection is complete.

Containers for a 24-hour urine collection.

In recent years, researchers have found that a single urine sample can provide the needed information. In the newer technique, the amount of albumin in the urine sample is compared with the amount of creatinine, a waste product of normal muscle breakdown. The measurement is called a urine albumin-tocreatinine ratio (UACR). A urine sample containing more than 30 milligrams of albumin for each gram of creatinine (30 mg/g) is a warning that there may be a problem. If the laboratory test exceeds 30 mg/g, another UACR test should be done 1 to 2 weeks later. If the second test also shows high levels of protein, the person has persistent proteinuria, a sign of declining kidney function, and should have additional tests to evaluate kidney function.

Cup for a single urine sample.

[Top]

What additional tests for kidney disease may be needed?

Tests that measure the amount of creatinine in the blood will show whether a persons kidneys are removing wastes efficiently. Having too much creatinine in the blood is a sign that a person has kidney damage. The doctor can use the creatinine measurement to estimate how efficiently the kidneys are filtering the blood. This calculation is called the estimated glomerular filtration rate, or eGFR. CKD is present when the eGFR is less than 60 milliliters per minute (mL/min). [Top]

What should a person with proteinuria do?

If a person has diabetes, hypertension, or both, the first goal of treatment will be to control blood glucose, also called blood sugar, and blood pressure. People with diabetes should test their blood glucose often, follow a healthy eating plan, take prescribed medicines, and get the amount of exercise recommended by their doctor. A person with diabetes and high blood pressure may need a medicine from a class of drugs called angiotensin-converting enzyme (ACE) inhibitors or a similar class called angiotensin receptor blockers (ARBs). These drugs have been found to protect kidney function even more than other drugs that provide the same level of blood pressure control. Many patients with proteinuria but without hypertension may also benefit from ACE inhibitors or ARBs. The American Diabetes Association and the American College of Cardiology recommend that people with diabetes keep their blood pressure below 3 130/80. People who have high blood pressure and proteinuria, but not diabetes, also benefit from taking an ACE inhibitor or ARB. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that people with kidney disease keep their blood pressure below 4 130/80. To maintain this target, a person may need to take a combination of two or more blood pressure medicines. A doctor may also prescribe a diuretic in addition to an ACE inhibitor or ARB. Diuretics are also called "water pills" because they help a person urinate and get rid of excess fluid in the body. In addition to blood glucose and blood pressure control, the National Kidney Foundation recommends restricting dietary salt and protein. A doctor may refer a patient to a dietitian to help develop and follow a healthy eating plan.
3

American Diabetes Association/American College of Cardiology. Hypertension in diabetes. Diabetes & Cardiovascular Disease Review.

2002; Issue 2.
4

National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection,

Evaluation, and Treatment of High Blood Pressure. Bethesda, MD: National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services; 2004.

[Top]

Points to Remember
Proteinuria is a condition in which urine contains a detectable amount of protein. Proteinuria is a sign of chronic kidney disease (CKD). Groups at risk for proteinuria include African Americans, American Indians, Hispanics/Latinos, Pacific Islander Americans, older people, overweight people, people with diabetes or hypertension, and people who have a family history of kidney disease. Proteinuria may have no signs or symptoms. Laboratory testing is the only way to find out whether protein is in a person's urine. Several health organizations recommend regular checks for proteinuria so kidney disease can be detected and treated before it progresses. A person with diabetes, hypertension, or both should work to control blood glucose and blood pressure. [Top]

Hope through Research

In recent years, researchers have learned much about kidney disease. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsors several programs aimed at understanding kidney failure and finding treatments to stop its progression.

The NIDDK's Division of Kidney, Urologic, and Hematologic Diseases supports basic research into normal kidney function and the diseases that impair normal function at the cellular and molecular levels, including diabetes, high blood pressure, glomerulonephritis, and other diseases marked by proteinuria. Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research. For information about current studies, visit www.ClinicalTrials.gov. [Top]

Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine (at least 2.5 or 3 L over 24 hours in adults).
Diabetic nephropathy is a clinical syndrome characterized by the following: Persistent albuminuria (>300 mg/d or >200 g/min) that is confirmed on at least 2 occ asions 3-6 months apart Progressive decline in the glomerular filtration rate (GFR) Elevated arterial blood pressure (see Workup) Proteinuria was first recognized in diabetes mellitus in the late 18th century. In the 1930s, Kimmelstiel and Wilson described the classic lesions of nodular glomerulosclerosis in diabetes associated with proteinuria and hypertension. (See Pathophysiology.) By the 1950s, kidney disease was clearly recognized as a common complication of diabetes, with as many as 50% of patients with diabetes of more than 20 years having this complication. (See Epidemiology.) Currently, diabetic nephropathy is the leading cause of chronic kidney disease in the United States and other Western societies. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD) cases in the United States. (See Prognosis.) Generally, diabetic nephropathy is considered after a routine urinalysis and screening for microalbuminuria in the setting of diabetes. Patients may have physical findings associated with longstanding diabetes mellitus. (See Clinical Presentation.) Good evidence suggests that early treatment delays or prevents the onset of diabetic nephropathy or diabetic kidney disease. (See Treatment and Management.) Regular outpatient follow-up is key in managing diabetic nephropathy successfully. (See Long-term Monitoring.)

UJI PROTEIN
Tujuan Untuk mengetahui adanya protein didalam urin Dasar Protein adalah sumber asam amino yang mengandung unsur C,H,O dan N . Protein sangat penting sebagai sumber asam amino yang digunakan untuk membangun struktur tubuh. Selain itu protein juga bisa digunakan sebagai sumber energi bila terjadi defisiensi energi dari karbohidrat dan/atau lemak. Sifat-sifat protein beraneka

ragam, dituangkan dalam berbagai sifatnya saat bereaksi dengan air, beberapa reagen dengan pemanasan serta beberapa perlakuan lainnya. Urin terdiri dari air dengan bahan terlarut berupa sisa metabolisme (seperti urea), garam terlarut, dan materi organik. Cairan dan materi pembentuk urin berasal dari darah atau cairan interstisial. Komposisi urin berubah sepanjang proses reabsorpsi. Biasanya, hanya sebagian kecil protein plasma disaring di glomerulus yang diserap oleh tubulus ginjal dan diekskresikan ke dalam urin. Normal ekskresi protein biasanya tidak melebihi 150 mg/24 jam atau 10 mg/dl urin. Lebih dari 10 mg/dl didefinisikan sebagai proteinuria. Adanya protein dalam urine disebut proteinuria. Beberapa keadaan yang dapat menyebabkan proteinuria adalah : penyakit ginjal (glomerulonefritis, nefropati karena diabetes, pielonefritis, nefrosis lipoid), demam, hipertensi, multiple myeloma, keracunan kehamilan (pre-eklampsia, eklampsia), infeksi saluran kemih (urinary tract infection). Proteinuria juga dapat dijumpai pada orang sehat setelah kerja jasmani, urine yang pekat atau stress karena emosi. Untuk mengetahui adanya protein di dalam urin dilakukan pemeriksaan. Prinsip dari pemeriksaan ini terjadi endapan urine jika direaksikan dengan asam sulfosalisila. Proteinuria didefinisikan sebagai konsentrasi protein sebesar 0.19/L (> +2 dengan cara dipstik) atau lebih dalam sekurang-kurangnya dua kali spesimen urin yang dikumpulkan sekurang-kurangnya dengan jarak 6 jam. Pada spesimen urin 24 jam, proteinuria didefinisikan sebagai suatu konsentrasi protein 0,3 per 24 jam. Tingginya kadar protein dalam urin ibu hamil dapat mengindikasikan terjadinya preeklampsi. Preeklampsi ialah penyakit dengan tanda-tanda hipertensi, edema dan proteinuria yang timbul karena kehamilan. Penyakit ini umumnya terjadi dalam trimester kedua -kehamilan. Tetapi dapat terjadi sebelumnya, misalnya pada molahidatidosa. Preeklampsia merupakan suatu kondisi spesifik kehamilandimana hipertensi terjadi setelah minggu ke-20 pada wanita yang sebelumnya memiliki tekanan darah normal (Bobak , 2004).Pemeriksaan protein urin dibutuhkan oleh ibu hamil bila dicurigai mengalami preeklampsi ringan atau berat, dari hasil pemeriksaan ini kita dapat memberikan asuhan kepada ibu hamil yangditujukan untuk mencegah timbulnya masalah potensial yaitu terjadinya eklampsi. Penetapam kadar protein dalam urin biasanya dinyatakan berdasarkan timbulnya kekeruhan pada urin. Karena padatnya atau kasarnya kekeruhan itu menjadi satu ukuran untuk jumlah protein yang ada, maka menggunakan urinyang jernih menjadi syarat yang penting.Salah satu uji protein urin yang cukup peka adalah dengan melalui pemanasan urin dengan asam asetat. Pemberian asam asetat dilakukan untuk mencapai atau mendekati titik iso-elektrik protein, sedangkan pemanasan bertujuan untuk denaturasi sehingga terjadilah presipitasi. Proses presipitasi dibantu oleh adanya garam-garam yang telah ada dalam urin atau yang sengajaditambahkan ke dalam urin. Asam asetat yang dipakai tidak pentingkonsentrasinya, konsentrasi antara 3-6% boleh dipakai, yang penting ialah pHyang dicapai melalui pemberian asam asetat. Urin encer yang mempunyai berat jenis rendah tidak baik digunakan untuk percobaan ini. Hasil terbail padapercobaan ini diperoleh dengan penggunaan urin asam. Ditemukannya protein urine merupakan tanda paling sering di jumpai pada preeklamsi, penyakit ginjal, bahkan sering merupakan petunjuk dini dari latent glomerulo nephitis,Toxemia gravidarum ataupun diabetic nephropathy. Selama kehamilan normal terdapat kenaikan hemodinamika ginjal dan di ikuti dengan tekanan venarenalis. Pembentukan urine dimulai dalam glomerulus, apabila filtrasi glomerulus mengalami kebocoran yang hebat, molekul protein besar akan terbuang dalam urin sehingga menyebabkan proteinuria. Pada pasien yang telah menderita penyakit parenkhim ginjal, Faktor kehamilan yang memasuki usia 20 minggu ini mungkin akan memperberat kebocoran protein melalui urine. Tujuan dari penelitian ini adalah untuk mengetahui gambaran protein urine pada ibu hamil trimester II yang memeriksakan diri di bidan praktek swasta Citra Mulia Kudus. Penelitian ini di laksanakan pada bulan Mei 2010 dengan jumlah sampel di ambil secara purposif dan sampel di periksa secara semi kuntitatif dengan metode statistik. Hasil penelitian menunjukan pemeriksaan urine pada ibu hamil trimester II yang negative sebanyak 9 sampel. Positif satu sebanyak 19 sampel dan positif dua sebanyak dua sampel. Pada

pengukuran tekanan darah terdapat 6 ibu hamil yang mengalami hipertensi dan dilihat dari kondisi kaki terdapat 3 orang ibu hamil yang mengalami edema. Berdasarkan hasil penelitian tersebut di harapkan kepada ibu hamil agar melakukan pemeriksaaan kehamilan secara rutin sehingga perkembangan janin dapat dipantau. Kandungan urine bergantung keadaan kesehatan dan makanan sehari-hari yangdikonsumsi oleh masingmasing individu. Individu normal meempunyai pH antara5 sampai 7. Banyak faktor yang memperngaruhi pH urine seseorang adalah makanan sehari-hari dan ketidakseimbangan hormonal. Warna urine adalah kuning keemasan yang dianggap berasal dari emas.Fungsi utama urin adalah untuk membuang zat sisa seperti racun atauobat-obatan dari dalam tubuh. Anggapan umum menganggap urin sebagai zat yang kotor. Hal ini berkaitan dengan kemungkinan urin tersebut berasal dari ginjal atau saluran kencing yang terinfeksi, sehingga urinnyapun akan Mengandung bakteri.Cairan yang tersisa mengandung urea dalam kadar yang tinggi danberbagai senyawa yang berlebih atau berpotensi racun yang akan dibuangkeluar tubuh. Materi yang terkandung di dalam urin dapat diketahui melaluiurinalisis, yaitu suatu metode analisis zat-zat yang dimungkinkan terkandung didalam urin. Analisis urin secara fisik meliputi pengamatan warna urin, berat jeniscairan urin dan pH serta suhu urin. Sedangkan analisis kimiawi dapat meliputianalisis glukosa, analisis protein dan analisis pigmen empedu. Untuk analisis kandungan protein ada banyak sekali metode yang ditawarkan, mulai dari metode uji millon sampai kuprisulfa dan sodium basa. Yang terakhir adalahanalisis secara mikroskopik, sampel urin secara langsung diamati dibawahmikroskop sehingga akan diketahui zat-zat apa saja yang terkandung di dalamurin tersebut, misalnya kalsium phospat, serat tanaman, bahkan bakteri. Reabsorpsi asam amino terutama terjadi di bagian awal tubulus kontortus proksimal yang menyerupai proses absorpsi di usus halus. Karier utama dimembrane luminal merupakan kotransport Na+ sedangkan karier di basolateraltidak bergantung pada Na+. Na+ di pompa keluar sel oleh Na+, K+, ATP ase dan kemudian asam amino keluar sel melalui proses difusi fasilitasi menuju cairan intertisium. Proteinuria ditandai dengan adanya kekeruhan. Proteinuria ditentukan dengan berbagai cara yaitu: asam sulfosalisilat, pemanasan dengan asam asetat, carik celup (hanya sensitif terhadap albumin). Penetapan jumlah protein ditentukan dengan urin 24 jam atau 12 jam, dengan cara Esbach.

Pemeriksaan proteinuria
Untuk menguji adanya kekeruhan , periksalah tabung dengan cahayaberpantul dan dengan latar belakang yang hitam. Cara penilaian uji protein adalah sebagai berikut : a 1. 2. 3. 4. 5. 6. 7. 8. Cara pemanasan asam asetat Alat dan Bahan Alat : Tabung reaksi Penjepit tabung reaksi Rak tabung Pipet tetes Corong Pipet volume Lampu spiritus/ Bunsen Beker glass Bahan :

1. 2. 1. 2. 3. 4. 5. 6. 7. b

Asam Asetat 6% Urin patologis Cara Kerja Isi urine normal pada tabung 1 dan urin patologis pada tabung 2 hingga dua per tiga tabung Kedua tabung di miringkan, panaskan bagian atas urin sampai mendidih Perhatikan apakah terjadi kekeruhan dibagian atas urin tersebut dengan cara membandingkan dengan urin bagian bawah. Jika urine dalam tabung tidak terjadi kekeruahn maka hasilnya negative jika urin dalam dalam tabung terjadi kekeruhan maka tambahkan asam asetat 6% sebanyak 3-5 tetes. Panaskan lagi sampai mendidih, Jika urine kembali bening/kekeruahn menghilang maka hasilnya negatif. Jika kekeruahn urin tetap ada maka hasilnya positif. Beri penilaian terhadap hasil pemeriksaan tersebut Cara menilai hasil : Tak ada kekeruhan :Ada kekeruhan ringan tanpa butir-butir : + (protein 0,01-0,05%) Kekeruhan mudah terlihat dengan butir-butir : ++ (protein 0,05-0,2%) Kekeruhan jelas dan berkeping-keping : +++ (protein 0,2-0,5%) Sangat keruh, berkeping besar atau bergumpal : ++++(> 0,5%) Prosedur yang lain :

1. Dengan Dipstick Urin sewaktu

1. Kumpulkan spesimen acak (random)/urin sewaktu. 2. Celupkan strip reagen (dipstick) kedalam urin. 3. Tunggu selama 60 detik, amati perubahan warna yang terjadi dan cocokkan dengan bagan warna.
Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual. Dipstick mendeteksi protein dengan indikator warna Bromphenol biru, yang sensitif terhadap albumin tetapi kurang sensitif terhadap globulin, protein Bence-Jones, dan mukoprotein.

1. 2. 3. 4.

Spesimen urin 24 jam Kumpulkan urin 24 jam masukkan dalam wadah besar dan simpan dalam lemari pendingin. Jika perlu, tambahkan bahan pengawet. Ukur kadar protein dengan metodekolorimetri menggunakan fotometer atau analyzer kimiawi otomatis.

1. Dengan asam sulfosalisil: 1. Dua tabung reaksi diisi masing-masingnya dengan dua ml urin yang akan diperiksa. 2. Tabung yg pertama ditambahkan 8 tetes larutan Asam sulfosalisil 20% dan kemudian dikocok. 3. Bandingkan dengan tabung yang kedua (yang tidak ditambahkan As. sulfosalisil 20%). Kalau tetap sama jernihnya test terhadap protein Negatif/ (-). 4. Jika tabung pertama lebih keruh dari tabung kedua, panasilah tabung pertama itu diatas nyala api sampai mendidih dan kemudian dinginkan kembali dengan air mengalir : Jika kekeruhan tetap ada pada waktu pemanasan dan tetap ada juga setelah dingin kembali, tes terhadap protein Positif. Jika kekeruhan itu hilang pada saat pemanasan &muncul lagi setelah dingin, lakukan pemeriksaan Bence Jones.

UJI GLUKOSA
Tujuan : Untuk mengetahui adanya glukosa di dalam urin Dasar : Glukosa mempunyai sifat mereduksi. Ion cupri direduksi menjadi cupro dan mengendap dalam bentuk merah bata. Semua larutan sakar yang mempunyai gugusan aldehid atau keton bebas akan memberikan reaksi positif. Na sitrat dan Na karbonat (basa yang tidak begitu kuat) berguna untuk mencegah pengendapan Cu++ . Sukrosa memberikan reaksi negative karena tidak mempunyai gugusan aktif (aldehid/ke ton bebas). Glukosa dalam urin ditentukan dengan reaksi reduksi menggunakan reagen Benedict (terbaik), Fehling dan Nylander. Cara lainnya adalah menggunakan carik celup. Reaksi benedict sensitive karena larutan sakar dalam jumlah sedikit menyebabkan perubahan warna dari seluruh larutan, sedikit menyebabkan perubahan warna dari seluruh larutan, hingga praktis lebih mudah mengenalnya. Hanya terlihat sedikit endapan pada dasar tabung. Uji benedict lebih peka karena benedict dapat dipakai untuk menafsir kadar glukosa secara kasar, karena dengan berbagai kadar glukosa memberikan warna yang berlainan.

Hasil pemeriksaan reduksi untuk urin 1. Cara benedict Alat dan Bahan Alat : 1. Tabung reaksi 2. Penjepit tabung reaksi 3. Rak tabung 4. Pipet tetes 5. Corong 6. Pipet volume 7. Lampu spiritus/ Bunsen 8. Beker glass Bahan : 1. 5 cc larutan benedict 2. Urine patologis 1. 2. 3. 4. Cara Kerja Masukkan larutan benedict ke dalam tabung reaksi sebanyak 5 cc Campurkan urin patologis 5 8 tetes ke dalam tabung yang telah berisi benedict Panaskan tabung di atas spritus/Bunsen dan sambil dikocok perlahan sampai mendidih Dinginkan dan amati terjadi perubahan warna atau tidak Cara menilai hasil : Negatif (-) : Tetap biru atau sedikit kehijau-hijauan Positif (+) : Hijau kekuning-kuningan dan keruh (0,5-1% glukosa) Positif (++) : Kuning keruh (1-1,5% glukosa) Positif (+++) : Jingga atau warna lumpur keruh (2-3,5% glukosa) Positif (++++) : Merah keruh ( > dari 3,5 % glukosa)

Glukosa Urine Darah disaring oleh jutaan nefron, sebuah unit fungsional dalam ginjal. Hasil penyaringan (filtrat) berisi produk-produk limbah (mis. urea), elektrolit (mis. natrium, kalium, klorida), asam amino, dan

glukosa. Filtrat kemudian dialirkan ke tubulus ginjal untuk direabsorbsi dan diekskresikan; zat-zat yang diperlukan (termasuk glukosa) diserap kembali dan zat-zat yang tidak diperlukan kembali diekskresikan ke dalam urin. Kurang dari 0,1% glukosa yang disaring oleh glomerulus terdapat dalam urin (kurang dari 130 mg/24 jam). Glukosuria (kelebihan gula dalam urin) terjadi karena nilai ambang ginjal terlampaui (kadar glukosa darah melebihi 160-180 mg/dl atau 8,9-10 mmol/l), atau daya reabsorbsi tubulus yang menurun.Prosedur Uji glukosa urin konvensional menggunakan pereaksi Benedict atas dasar sifat glukosa sebagai zat pereduksi. Cara ini tidak spesifik karena beberapa pereduksi lain dapat mengacaukan hasil uji. Beberapa gula lain bisa menyebabkan hasil uji reduksi positif misalnya fruktosa, sukrosa, galaktosa, pentose, laktosa, dsb. Beberapa zat bukan gula yang dapat mengadakan reduksi seperti asam homogentisat, alkapton, formalin, glukoronat. Pengaruh obat : streptomisin, salisilat kadar tinggi, vitamin C, dsb. Metode carik celup (dipstick) dinilai lebih bagus karena lebih spesifik untuk glukosa dan waktu pengujian yang amat singkat. Reagen strip untuk glukosa dilekati dua enzim, yaitu glukosa oksidase (GOD) dan peroksidase (POD), serta zat warna (kromogen) seperti orto-toluidin yang akan berubah warna biru jika teroksidasi. Zat warna lain yang digunakan adalah iodide yang akan berubah warna coklat jika teroksidasi. Prosedur uji yang akan dijelaskan di sini adalah uji dipstick. Kumpulkan spesimen acak (random)/urin sewaktu. Celupkan strip reagen (dipstick) ke dalam urin. Tunggu selama 60 detik, amati perubahan warna yang terjadi dan cocokkan dengan bagan warna. Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual. Beberapa faktor yang dapat mempengaruhi hasil uji dipstick adalah : Hasil uji positif palsu dapat disebabkan oleh : bahan pengoksidasi (hidrogen peroksida, hipoklorit, atau klorin) dalam wadah sampel urin, atau urine yang sangat asam (pH di bawah 4) Hasil negatif palsu dapat disebabkan oleh : pengaruh obat (vitamin C, asam hogentisat, salisilat dalam jumlah besar, asam hidroksiindolasetat), berat jenis urine > 1,020 dan terutama bila disertai dengan pH urine yang tinggi, adanya badan keton dapat mengurangi sensitivitas pemeriksaan, infeksi bakteri. Nilai Rujukan Uji glukosa urin normal = negatif (kurang dari 50mg/dl) Masalah Klinis Glukosuria umumnya berarti diabetes mellitus. Namun, glukosuria dapat terjadi tidak sejalan dengan peningkatan kadar glukosa dalam darah; oleh karena itu glukosuria tidak selalu dapat dipakai untuk

menunjang diagnosis diabetes mellitus. Jika nilai ambang ginjal begitu rendah bahkan kadar glukosa darah normal menghasilkan kondisi glukosuria, keadaan ini disebut sebagai glycosuria ginjal. ================================================================ Protein Urine Biasanya, hanya sebagian kecil protein plasma disaring di glomerulus yang diserap oleh tubulus ginjal dan diekskresikan ke dalam urin. Dengan menggunakan spesimen urin acak (random) atau urin sewaktu, protein dalam urin dapat dideteksi menggunakan strip reagen (dipstick). Normal ekskresi protein biasanya tidak melebihi 150 mg/24 jam atau 10 mg/dl urin. Lebih dari 10 mg/dl didefinisikan sebagai proteinuria. Sejumlah kecil protein dapat dideteksi pada urin orang yang sehat karena perubahan fisiologis. Selama olah raga, stres atau diet yang tidak seimbang dengan daging dapat menyebabkan proteinuria transien. Pra-menstruasi dan mandi air panas juga dapat menyebabkan proteinuria. Bayi baru lahir dapat mengalami peningkatan proteinuria selama usia 3 hari pertama. Prosedur 1. Spesimen urin acak (random)Kumpulkan spesimen acak (random)/urin sewaktu. Celupkan strip reagen (dipstick) ke dalam urin. Tunggu selama 60 detik, amati perubahan warna yang terjadi dan cocokkan dengan bagan warna. Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual.Dipstick mendeteksi protein dengan indikator warna Bromphenol biru, yang sensitif terhadap albumin tetapi kurang sensitif terhadap globulin, protein Bence-Jones, dan mukoprotein. 2. Spesimen urin 24 jamKumpulkan urin 24 jam, masukkan dalam wadah besar dan simpan dalam lemari pendingin. Jika perlu, tambahkan bahan pengawet. Ukur kadar protein dengan metode kolorimetri menggunakan fotometer atau analyzer kimiawi otomatis. Nilai Rujukan Urin acak : negatif (15 mg/dl) Urin 24 jam : 25 150 mg/24 jam. Masalah Klinis Pengukuran proteinuria dapat dipakai untuk membedakan antara penderita yang memiliki risiko tinggi menderita penyakit ginjal kronik yang asimptomatik dengan yang sehat. Proteinuria yang persistent (tetap +1, dievaluasi 2-3x / 3 bulan) biasanya menunjukkan adanya kerusakan ginjal. Proteinuria persistent juga akan memberi hasil +1 yang terdeteksi baik pada spesimen urine pagi maupun urine sewaktu setelah melakukan aktivitas. Protein terdiri atas fraksi albumin dan globulin. Peningkatan ekskresi albumin merupakan petanda yang sensitif untuk penyakit ginjal kronik yang disebabkan karena penyakit glomeruler, diabetes

mellitus, dan hipertensi. Sedangkan peningkatan ekskresi globulin dengan berat molekul rendah merupakan petanda yang sensitif untuk beberapa tipe penyakit tubulointerstitiel. Proteinuria positif perlu dipertimbangkan untuk analisis kuantitatif protein dengan menggunakan sampel urine tampung 24 jam. Jumlah proteinuria dalam 24 jam digunakan sebagai indikator untuk menilai tingkat keparahan ginjal. Proteinuria rendah (kurang dari 500mg/24jam). Pengaruh obat : penisilin, gentamisin, sulfonamide, sefalosporin, media kontras, tolbutamid (Orinase), asetazolamid (Diamox), natrium bikarbonat. Proteinuria sedang (500-4000 mg/24 jam) dapat berkaitan dengan glomerulonefritis akut atau kronis, nefropati toksik (toksisitas obat aminoglikosida, toksisitas bahan kimia), myeloma multiple, penyakit jantung, penyakit infeksius akut, preeklampsia. Proteinuria tinggi (lebih dari 4000 mg/24 jam) dapat berkaitan dengan sindrom nefrotik, glomerulonefritis akut atau kronis, nefritis lupus, penyakit amiloid. Faktor yang Dapat Mempengaruhi Temuan Laboratorium Hasil positif palsu dapat disebabkan oleh hematuria, tingginya substansi molekular, infus polivinilpirolidon (pengganti darah), obat (lihat pengaruh obat), pencemaran urine oleh senyawa ammonium kuaterner (pembersih kulit, klorheksidin), urine yang sangat basa (pH > 8) Hasil negatif palsu dapat disebabkan oleh urine yang sangat encer, urine sangat asam (pH di bawah 3) ======================================================== Keton Urine Badan keton terdiri dari 3 senyawa, yaitu aseton, asam aseotasetat, dan asam -hidroksibutirat, yang merupakan produk metabolisme lemak dan asam lemak yang berlebihan. Badan keton diproduksi ketika karbohidrat tidak dapat digunakan untuk menghasilkan energi yang disebabkan oleh : gangguan metabolisme karbohidrat (mis.diabetes mellitus yang tidak terkontrol), kurangnya asupan karbohidrat (kelaparan, diet tidak seimbang : tinggi lemak rendah karbohidrat), gangguan absorbsi karbohidrat (kelainan gastrointestinal), atau gangguan mobilisasi glukosa, sehingga tubuh mengambil simpanan asam lemak untuk dibakar. Peningkatan kadar keton dalam darah akan menimbulkan ketosis sehingga dapat menghabiskan cadangan basa (mis. bikarbonat, HCO3) dalam tubuh dan menyebabkan asidosis. Pada ketoasidosis diabetik, keton serum meningkat hingga mencapai lebih dari 50 mg/dl.Keton memiliki struktur yang kecil dan dapat diekskresikan ke dalam urin. Namun, kenaikan kadarnya pertama kali tampak pada plasma atu serum, kemudian baru urin. Ketonuria (keton dalam urin) terjadi akibat ketosis. Benda keton yang dijumpai di urine terutama adalah aseton dan asam asetoasetat. Prosedur

Kumpulkan spesimen urine secara acak (urin random atau urin sewaktu). Urin harus segar dan ditampung dalam wadah tertutup rapat. Pengujian harus segera dilakukan, karena penundaan pengujian lebih lama dapat menyebabkan temuan negatif palsu. Hal ini dikarenakan keton mudah menguap. Uji ketonuria dapat dilakukan dengan menggunakan tablet Acetest, atau strip reagen (dipstick) Ketostix atau strip reagen multitest (mis. Combur, Multistix, Arkray, dsb). Uji ketonuria dengan tablet Acetest digunakan untuk mendeteksi dua keton utama, yaitu aseton dan asam asetoasetat. Letakkan tablet Acetest di atas kertas saring atau tissue, lalu teteskan urin segar di atas tablet tersebut. Tunggu selama 30 detik. Amati perubahan warna yang terjadi pada tablet tersebut; jika berubah warna menjadi berwarna lembayung terang gelap, maka uji keton dinyatakan positif. Uji ketonuria dengan strip reagen (Ketostix atau strip reagen multitest) lebih sensitif terhadap asam asetoasetat daripada aseton. Celupkan strip reagen ke dalam urin. Tunggu selam 15 detik, lalu amati perubahan warna yang terjadi. Bandingkan dengan bagan warna. Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual. Nilai Rujukan Dewasa dan anak : uji keton negatif (kurang dari15 mg/dl) Masalah Klinis Uji keton positif dapat dijumpai pada : Asidosis diabetic (ketoasidosis), kelaparan atau malnutrisi, diet rendah karbohidrat, berpuasa, muntah yang berat, pingsan akibat panas, kematian janin. Pengaruh obat : asam askorbat, senyawa levodopa, insulin, isopropil alkohol, paraldehida, piridium, zat warna yang digunakan untuk berbagai uji (bromsulfoftalein dan fenosulfonftalein). Faktor yang Dapat Mempengaruhi Hasil Laboratorium Diet rendah karbohidrat atau tinggi lemak dapat menyebabkan temuan positif palsu. Obat tertentu (Lihat pengaruh obat) Urin disimpan pada temperature ruangan dalam waktu yang lama dapat menyebabkan hasil uji negaif palsu Adanya bakteri dalam urin dapat menyebabkan kehilangan asam asetoasetat Anak penderita diabetes cenderung mengalami ketonuria daripada penderita dewasa. =========================================================

Bilirubin Urine Secara normal, bilirubin tidak dijumpai di urin. Bilirubin terbentuk dari penguraian hemoglobin dan ditranspor ke hati, tempat bilirubin berkonjugasi dan diekskresi dalam bentuk empedu. Bilirubin terkonjugasi (bilirubin direk) ini larut dalam air dan diekskresikan ke dalam urin jika terjadi

peningkatan kadar di serum. Bilirubin tak terkonjugasi (bilirubin indirek) bersifat larut dalam lemak, sehingga tidak dapat diekskresikan ke dalam urin. Prosedur Uji bilirubinuria dapat menggunakan reaksi diazo (dengan tablet atau dipstick), atau uji Fouchet (Harison spot test) dengan feri klorida asam (FeCl2). Uji bilirubinuria dengan reaksi diazo banyak dipakai karena lebih praktis dan lebih sensitif. Di antara dua macam uji diazo, uji tablet (mis. tablet Ictotest) lebih sensitif daripada dipstick. 1. Reaksi diazoKumpulkan spesimen urin pagi atau urin sewaktu/acak (random). Celupkan stik reagen (dipstick) atau tablet Ictotest. Tunggu 30 detik, lalu bandingkan warnanya dengan bagan warna pada botol reagen. Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual. 2. Uji FouchetKe dalam 12 ml urin, tambahkan 3 ml barium klorida dan 3 tetes ammonium sulfat jenuh. Centrifuge selama 5 menit dengan kecepatan 3500 rpm. Buang supernatant, tambahkan 2 tetes larutan Fouchet pada endapan. Amati perubahan warna yang terjadi.Reaksi negatif jika tidak tampak perubahan warna. Reaksi positif jika terjadi perubahan warna : hijau atau biru. Pengujian harus dilakukan dalam waktu 1 jam, dan urin harus dihindarkan dari pajanan sinar matahari (sinar ultraviolet) langsung agar bilirubin tidak teroksidasi menjadi biliverdin. Nilai Rujukan Normal : negatif (kurang dari 0.5mg/dl) Masalah Klinis Bilirubinuria (bilirubin dalam urin) mengindikasikan gangguan hati atau saluran empedu, seperti pada ikterus parenkimatosa (hepatitis infeksiosa, toksik hepar), ikterus obstruktif, kanker hati (sekunder), CHF disertai ikterik. Urin yang mengadung bilirubin yang tinggi tampak berwarna kuning pekat, dan jika digoncang-goncangkan akan timbul busa. Obat-obatan yang dapat menyebabkan bilirubinuria : Fenotiazin klorpromazin (Thorazine), asetofenazin (Tindal), klorprotiksen (Taractan), fenazopiridin (Pyridium), klorzoksazon (Paraflex). Faktor yang Dapat Mempengaruhi Temuan Laboratorium 1. Uji dengan reaksi Diazo Reaksi negatif palsu terjadi bila urin mengandung banyak asam askorbat (vitamin C), kadar nitrit dalam urine meningkat, asam urat tinggi, serta bila bilirubin teroksidasi menjadi biliverdin akibat spesimen urin terpajan sinar matahari (ultraviolet) langsung. Hasil positif palsu dapat dijumpai pada pemakaian obat yang menyebabkan urine menjadi berwarna merah (lihat pengaruh obat 2. Uji Fouchet

Reaksi negative palsu terjadi bila bilirubin teroksidasi menjadi biliverdin akibat penundaan pemeriksaan. Reaksi positif palsu oleh adanya metabolit aspirin, urobilin atau indikan, urobilinogen. ======================================================== Urobilinogen Urine Empedu, yang sebagian besar dibentuk dari bilirubin terkonjugasi mencapai area duodenum, tempat bakteri usus mengubah bilirubin menjadi urobilinogen. Sejumlah besar urobilinogen berkurang di faeses, sejumlah besar kembali ke hati melalui aliran darah; di sini urobilinogen diproses ulang menjadi empedu, dan kira-kira sejumlah 1% diekskresikan oleh ginjal ke dalam urin. Ekskresi urobilinogen ke dalam urine kira-kira 1-4 mg/24jam. Ekskresi mencapai kadar puncak antara jam 14.00 16.00, oleh karena itu dianjurkan pengambilan sampel dilakukan pada jam-jam tersebut. Prosedur 1. Spesimen urin sewaktuUrine harus dalam keadaan masih segar dan harus segera diperiksa. Uji dapat dilakukan sebagai bagian dari analisis urin rutin, menggunakan strip reagen (dipstick) atau pereaksi Erlich. Celupkan strip reagen ke dalam urin, tunggu 30 detik. Amati perubahan warna dan bandingkan dengan bagan warna. Pembacaan dipstick dengan instrument otomatis lebih dianjurkan untuk memperkecil kesalahan dalam pembacaan secara visual. 2. Spesimen urin 2 jamKumpulkan specimen urin di antara jam 13.00 15.00, atau antara jam 14.00 16.00, karena urobilinogen mencapai puncaknya di siang hari pada jam-jam tersebut. Urin harus disimpan dalam lemari pendingin dan tempat yang gelap; urin harus segera diperiksa dalam 30 menit karena urobilinogen dapat teroksidasi menjadi urobilin (zat oranye). Uji dapat dilakukan dengan menggunakan strip reagen (dipstick). 3. Spesimen urin 24 jamKumpulkan urin 24 jam, masukkan dalam wadah besar dan simpan dalam lemari pendingin. Jika perlu tambahkan bahan pengawet. Jauhkan urin dari pajanan cahaya. Tunda pemberian obat yang dapat mempengaruhi hasil uji selama 24 jam atau sampai uji selesai dilakukan. Jika obat memang harus diberikan, cantumkan nama obat tersebut pada formulir laboratorium. Uji dilakukan dengan menggunakan strip reagen (dipstick). Nilai Rujukan Urin acak : negatif (kurang dari 2mg/dl> Urin 2 jam : 0.3 1.0 unit Erlich Urin 24 jam : 0.5 4.0 unit Erlich/24jam, atau 0,09 4,23 mol/24 jam (satuan SI) Masalah Klinis Peningkatan ekskresi urobilinogen dalam urine terjadi bila fungsi sel hepar menurun atau terdapat kelebihan urobilinogen dalam saluran gastrointestinal yang melebehi batas kemampuan hepar untuk melakukan rekskresi. Urobilinogen meninggi dijumpai pada : destruksi hemoglobin berlebihan (ikterik hemolitika atau anemia hemolitik oleh sebab apapun), kerusakan parenkim hepar (toksik hepar, hepatitis infeksiosa,

sirosis hepar, keganasan hepar), penyakit jantung dengan bendungan kronik, obstruksi usus, mononukleosis infeksiosa, anemia sel sabit. Hasil positif juga dapat diperoleh setelah olahraga atau minum atau dapat disebabkan oleh kelelahan atau sembelit. Orang yang sehat dapat mengeluarkan sejumlah kecil urobilinogen. Urobilinogen urine menurun dijumpai pada ikterik obstruktif, kanker pankreas, penyakit hati yang parah (jumlah empedu yang dihasilkan hanya sedikit), penyakit inflamasi yang parah, kolelitiasis, diare yang berat. Faktor yang Dapat Mempengaruhi Temuan Laboratorium 1. Reaksi positif palsu Pengaruh obat : fenazopiridin (Pyridium), sulfonamide, fenotiazin, asetazolamid (Diamox), kaskara, metenamin mandelat (Mandelamine), prokain, natrium bikarbonat, pemakaian pengawet formaldehid. Makanan kaya karbohidrat dapat meninggikan kadar urobilinogen, oleh karena itu pemeriksaan urobilinogen dianjurkan dilakukan 4 jam setelah makan. Urine yang bersifat basa kuat dapat meningkatkan kadar urobilinogen; urine yang dibiarkan setengah jam atau lebih lama akan menjadi basa. 2. Reaksi negatif palsu Pemberian antibiotika oral atau obat lain (ammonium klorida, vitamin C) yang mempengaruhi flora usus yang menyebabkan urobilinogen tidak atau kurang terbentuk dalam usus, sehingga ekskresi dalam urine juga berkurang. Paparan sinar matahari langsung dapat mengoksidasi urobilinogen menjadi urobilin. Urine yang bersifat asam kuat.
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Background
Nephrotic syndrome is kidney disease with proteinuria, hypoalbuminemia, and edema. Nephrotic-range proteinuria is 3 grams per day or more. On a single spot urine collection, it is 2 g of protein per gram of urine creatinine. There are many specific causes of nephrotic syndrome. These include kidney diseases such as minimalchange nephropathy, focal glomerulosclerosis, andmembranous nephropathy. Nephrotic syndrome can also result from systemic diseases that affect other organs in addition to the kidneys, such as diabetes, amyloidosis, and lupus erythematosus. Nephrotic syndrome may affect adults and children, of both sexes and of any race. It may occur in typical form, or in association with nephritic syndrome. The latter connotes glomerular inflammation, with hematuria and impaired kidney function.

Classification
Nephrotic syndrome can be primary, being a disease specific to the kidneys, or it can be secondary, being a renal manifestation of a systemic general illness. In all cases, injury to glomeruli is an essential feature. Primary causes of nephrotic syndrome include the following, in approximate order of frequency:

Minimal-change nephropathy Focal glomerulosclerosis Membranous nephropathy Hereditary nephropathies Secondary causes include the following, again in order of approximate frequency: Diabetes mellitus Lupus erythematosus Amyloidosis and paraproteinemias Viral infections (eg, hepatitis B, hepatitis C, human immunodeficiency virus [HIV] ) Preeclampsia Nephrotic-range proteinuria may occur in other kidney diseases, such as IgA nephropathy. In that common glomerular disease, one third of patients may have nephrotic-range proteinuria.[1] Nephrotic syndrome may occur in persons with sickle cell disease and evolve to renal failure. Membranous nephropathy may complicate bone marrow transplantation, in association with graft versus host disease. Kidney diseases that affect tubules and interstitium, such as interstitial nephritis, will not cause nephrotic syndrome. The above causes of nephrotic syndrome are largely those for adults, and this article will concentrate primarily on adult nephrotic syndrome. However, nephrotic syndrome in infancy and childhood is an important entity. For discussion of this topic, see the Medscape Reference article Pediatric Nephrotic Syndrome. From a therapeutic perspective, nephrotic syndrome may be classified as steroid sensitive, steroid resistant, steroid dependent, or frequently relapsing. Corticosteroids (prednisone), cyclophosphamide, and cyclosporine are used to induce remission in nephrotic syndrome. Diuretics are used to reduce edema. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers are administered to reduce proteinuria. (See Treatment and Medication.) patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings most often are local (eg, reflecting kidney inflammation or mass), result from the systemic effects of kidney dysfunction, or affect urination (eg, changes in urine itself or in urine production). History History plays a limited role because symptoms are nonspecific. Hematuria is relatively specific for a GU disorder, but patients who report red urine may instead have one of the following:
Myoglobinuria Hemoglobinuria Porphyrinuria Porphobilinuria Food-induced urine coloring (some foods, eg, beets, rhubarb, sometimes food coloring, may make urine appear red)

Drug-induced urine coloring (some drugs, most commonly phenazopyridine , but sometimes cascara, diphenylhydantoin, methyldopa , phenacetin, phenindione, phenolphthalein, phenothiazines, and senna

may make urine appear red)

High concentrations of urinary protein cause frothy or sudsy urine. Urinary frequency (see Symptoms of
Genitourinary Disorders: Urinary Frequency) should be distinguished from polyuria (see Symptoms of Genitourinary Disorders: Polyuria) in patients who report excessive urination. Nocturia may be a feature of

either but is often the result of excess fluid intake too close to bedtime or of chronic kidney disease. Family history is useful for identifying inheritance patterns and risk of polycystic kidney disease or other hereditary nephropathies (eg, hereditary nephritis, thin basement membrane disease, nail-patella syndrome, cystinuria, hyperoxaluria). Physical Examination Patients with moderate or severe chronic kidney disease sometimes appear pale, wasted, or ill. Deep (Kussmaul's) respirations suggest hyperventilation in response to metabolic acidosis with acidemia. Chest examination: Pericardial and pleuritic friction rubs may be signs of uremia. Abdominal examination: Visual fullness of the upper abdomen is an unusual, nonspecific finding of polycystic kidney disease. It may also indicate a kidney or abdominal mass or hydronephrosis. A soft, lateralizing bruit is occasionally audible in the epigastrium or the flank in renal artery stenosis; presence of a diastolic component increases the probability of renovascular hypertension. Pain elicited by mild striking of the back, flanks, and angle formed by the 12th rib and lumbar spine with a fist (costovertebral tenderness) may indicate pyelonephritis or urinary tract obstruction (eg, due to calculi). Normal kidneys are not usually palpable. However, in some women, the lower pole of the right kidney can occasionally be felt with palpation during deep inspiration, and large kidneys or masses can sometimes be felt without special maneuvers. In neonates, the kidneys can be felt with the thumbs when the thumbs are placed anterior and the fingers posterior to the costovertebral angle. Transillumination can distinguish solid from cystic renal masses in some children < 1 yr if the kidney and mass are manipulated against the abdominal wall. Skin examination: Chronic kidney disease can cause any of the following:
Xerosis due to sebaceous and eccrine sweat gland atrophy Pallor due to anemia

Hyperpigmentation due to melanin deposition Sallow or yellow-brown skin due to urochrome deposition Petechiae or ecchymoses due to platelet dysfunction

Uremic frost, the deposition of white-to-tan urea crystals on the skin after sweat evaporation, is rare. Neurologic examination: Patients with acute renal failure may be drowsy, confused, or inattentive; speech may be slurred. Asterixis can be detected in handwriting or by observation of outstretched hands maximally extended at the wrists; after several seconds in this position, a hand flap in the flexor direction is asterixis. Asterixis suggests one of the following:
Chronic kidney disease Chronic liver failure CO2 narcosis

Testing Urinalysis and measurement of serum creatinine are the initial steps in evaluation of renal disorders. Other urine, blood, and imaging tests (eg, ultrasonography, CT, MRI) are done in specific circumstances. Ideally, after the urethral meatus is cleaned, the urine specimen is collected midstream (clean-catch specimen) during the first void of the morning; the urine should be examined immediately because delays can lead to changes in test results. Bladder catheterization or suprapubic aspiration can be used for collection when urine cannot be obtained by spontaneous voiding or when vaginal material contaminates the urine specimen. However, the trauma of catheterization may falsely increase the number of RBCs in the specimen, so catheterization is usually avoided if the outcome of interest is microscopic hematuria. A specimen from a catheter collection bag is not acceptable for microscopic or bacteriologic tests. Urinalysis: A complete urinalysis includes the following:
Inspection for color, appearance, and odor Measurement of pH, specific gravity, protein, glucose, RBCs, nitrites, and WBC esterase by dipstick reagents Microscopic analysis for casts, crystals, and cells (urine sediment)

Bilirubin and urobilinogen, although standard parts of many dipstick tests, no longer play significant roles in evaluation of renal or hepatic disorders. Color is the most obvious of urine attributes, and observation of color is an integral part of urinalysis (see Table 1: Approach to the Genitourinary Patient: Causes Of Urine Color Changes possible causes and help direct additional testing. ). Urine color may suggest

Table 1

Causes Of Urine Color Changes

Color Cause

Red, orange, Bilirubin

or brown

Drugs (eg, cascara, diphenylhydantoin, levodopa, methyldopa , phenacetin,phenazopyridine , phenindione, phenolphthalein, phenothiazines,rifampin

, senna

) Foods (eg, beets) Free myoglobin Porphyrins RBCs Cloudy white Infection (pyuria) Lymph (chyluria) due to filariasis or to obstructed retroperitoneal lymphatics Precipitated phosphate crystals Green Drugs (eg, amitriptyline

,methylene blue ,propofol ) Pseudomonas infection Purple (rare) Gram-negative bacteria in urinary catheters* Dark brown or black Melanoma

* Rarely, urine in collection bags of catheterized bedbound patients turns purple (purple urine bag syndrome) when urinary gram-negative bacteria metabolize a tryptophan metabolite (indican) in alkaline urine into indigo; this reaction is clinically insignificant. Caused by oxidation of excessive homogentisic acid or melanogen when urine is exposed to air for several hours.

Odor, often unintentionally noted during visual inspection, conveys useful information only in rare cases of inherited disorders of amino acid metabolism when urine has a distinctive smell (eg, maple syrup in maple syrup urine disease, sweaty feet in isovaleric acidemia, tomcat urine in multiple carboxylase deficiency). pH is normally 5.0 to 6.0 (range 4.5 to 8.0). Measuring with a glass pH electrode is recommended when precise values are necessary for decision making, as when diagnosing renal tubular acidosis; in these cases, a layer of mineral oil should be added to the urine specimen to prevent escape of CO 2. Delay in

processing a specimen may elevate pH because ammonia is released as bacteria break down urea. Infection with urease-producing pathogens can spuriously increase pH. Specific gravity provides a rough measure of urine concentration (osmolality). Normal range is 1.001 to 1.035; values may be low in the elderly or in patients with impaired renal function, who are less able to concentrate urine. It is measured by hydrometer or refractometer or estimated with a dipstick. Accuracy of the dipstick test is controversial, but the test may be sufficient for patients who have calculi and are advised to self-monitor urine concentration to maintain dilute urine. Specific gravity by dipstick may be spuriously elevated when urine pH is < 6 or low when pH is> 7. Hydrometer and refractometer measurements may be elevated by high levels of large molecules (eg, radiopaque contrast agent, albumin, glucose, carbenicillin

) in the urine. Protein, detected by standard dipstick tests, reflects mainly urinary albumin concentration, classified as negative (< 10 mg/dL), trace (15 to 30 mg/dL), or 1+ (30 to 100 mg/dL) through 4+ (> 500 mg/dL). Microalbuminuria, an important marker for renal complications in patients with diabetes, is not detected by standard dipsticks, but special microalbumin dipsticks are available. Light-chain proteins (eg, due to multiple myeloma) also are not detected. Significance of proteinuria depends on total protein excretion rather than protein concentration estimated by dipstick; thus, when proteinuria is detected with dipstick testing, quantitative measures of urinary protein (see Symptoms of Genitourinary Disorders: Proteinuria) should be done. False-negative results can be caused by dilute urine. False-positive results can be caused by any of the following:
High pH (> 9) Presence of cells Radiopaque contrast agents Concentrated urine

Glucose usually appears in the urine when serum glucose increases to > 180 mg/dL (> 10.1 mmol/L) and renal function is normal. Threshold for detection by urine dipstick is 50 mg/dL (2.8 mmol/L). Any amount is abnormal. Falsely low or negative results can result from any of the following:
Ascorbic acid Ketones Aspirin

Levodopa Tetracycline

Very high urine pH Dilute urine

Hematuria is detected when RBCs lyse on a dipstick test strip, releasing Hb and causing a color change. Range is from negative (0) to 4+. Trace blood (corresponding to 3 to 5 RBCs/high-power field [HPF]) is normal under some circumstances (eg, exercise) in some people. Because the test strip reagent reacts with Hb, free Hb (eg, due to intravascular hemolysis) or myoglobin (eg, due to rhabdomyolysis) causes a positive result. Hemoglobinuria and myoglobinuria can be distinguished from hematuria by the absence of RBCs on microscopic examination and by the pattern of color change on the test strip. RBCs create a dotted or speckled pattern; free Hb and myoglobin create a uniform color change. Povidone iodine causes false-positive results (uniform coloring); ascorbic acid causes false-negative results. Nitrites are produced when bacteria reduce urinary nitrates derived from amino acid metabolism. Nitrites are not normally present and signify bacteriuria. The test is either positive or negative. False-negative results may occur with any of the following:
Infection with certain pathogens that cannot convert nitrate to nitrite (eg, Enterococcus faecalis,Neisseria gonorrhoeae, Mycobacterium tuberculosis, Pseudomonas sp) Urine that has not stayed long enough (< 4 h) in the bladder Low urinary excretion of nitrate Enzymes (of certain bacteria) that reduce nitrates to nitrogen High urine urobilinogen level Presence of ascorbic acid Urine pH < 6.0

Nitrites are used mainly with WBC esterase testing to monitor patients with recurrent urine infections, particularly children with vesicoureteral reflux, and sometimes to confirm the diagnosis of uncomplicated UTI in women of childbearing age. WBC esterase is released by lysed neutrophils. Its presence in urine reflects acute inflammation, most commonly due to bacterial infection but sometimes due to interstitial nephritis, nephrolithiasis, or renal TB. Threshold for detection is about 5 WBCs/HPF, and test results range from negative to 4+. The test is not very sensitive for detection of infection. Contamination of a urine specimen with vaginal flora is the most common cause of false-positive results. False-negative results may result from any of the following:
Very dilute urine Glycosuria

Urobilinogen Use of phenazopyridine , nitrofurantoin

, rifampin

, or large amounts of vitamin C

WBC esterase is used mainly with nitrite testing to monitor patients with recurrent urine infections and sometimes to diagnose uncomplicated UTI in women of childbearing age. If both tests are negative, the likelihood of a positive urine culture is small. Microscopic analysis: Detection of solid elements (cells, casts, crystals) requires microscopic analysis, ideally done immediately after voiding, and dipstick testing. The specimen is prepared by centrifuging 10 to 15 mL of urine at 1500 to 2500 rpm for 5 min. The supernatant is fully decanted; a small amount of urine remains with the residue at the bottom of the centrifuge tube. The residue can be mixed back into solution by gently agitating the tube or tapping the bottom. A single drop is pipetted onto a slide and covered with a coverslip. For routine microscopic analysis, staining is optional. The specimen is examined under reduced light with the low-power objective and under full-intensity light with the high-power objective; the latter is typically used for semiquantitative estimates (eg, 10 to 15 WBCs/HPF). Polarized light is used to identify some crystals and lipids in the urine. Phase-contrast microscopy enhances identification of cells and casts. Epithelial cells (renal tubular, transitional, squamous cells) frequently are found in urine; most common are squamous cells lining the end of the urethra and contaminants from the vagina. Only renal tubular cells are diagnostically important; however, except when found in casts, they are difficult to distinguish from transitional cells. A few renal tubular cell casts appear in normal urine, but a large number suggests tubular injury (eg, acute tubular necrosis, tubulointerstitial nephropathy, nephrotoxins, nephrotic syndrome). RBCs < 3/HPF may be normal (< 5/HPF is sometimes normal, eg, after exercise), and any hematuria should be interpreted in clinical context (see Symptoms of Genitourinary Disorders: Isolated Hematuria). On microscopic analysis, glomerular RBCs are dysmorphic, with spicules, folding, and blebs; nonglomerular RBCs retain their normal shape. WBCs < 5/HPF may be normal; special staining can distinguish eosinophils from neutrophils (see Approach to the Genitourinary Patient: Other urine tests). Pyuria is defined as > 5 WBCs /HPF in a sample of centrifuged urine.

Lipiduria is most characteristic of the nephrotic syndrome; renal tubular cells absorb filtered lipids, which appear microscopically as oval fat bodies, and cholesterol, which produces a Maltese cross pattern under polarized light. Lipids and cholesterol can also be free floating or incorporated into casts. Crystals in urine are common and usually clinically insignificant (see Table 2: Approach to the Genitourinary
Patient: Types of Urinary Crystals

). Crystal formation depends on all of the following:

Table 2

Types of Urinary Crystals

Type Appearance Comments

Ca oxalate

Occur in several shapes but are most easily recognized when they form small, octahedral, envelope-like shapes

When present in large numbers, strongly suggest ethylene glycol poisoning or, rarely, short bowel syndrome, hereditary oxalosis and oxaluria, or high doses of vitamin C Important in evaluation as potential constituents of calculi Diagnostic of cystinuria, a rare hereditary cause of calculi Often occur in normal alkaline urine or in urine of patients with struvite calculi Often present in acidic, cool, highly concentrated urine May indicate mild dehydration in neonates or tumor lysis syndrome in patients with cancer or renal failure

Cystine

Perfect hexagons, sometimes alone as flat plates or as overlapping crystals of varying sizes May resemble coffin lids or quartz crystals May be diamond- or needle-shaped or rhomboid, although uric acid may be amorphous

Mg ammonium phosphate Uric acid

Table 3

Drugs That Cause Crystal Formation

Drug Crystal Description

Acyclovir

Birefringent, needle-shaped May be free or engulfed in leukocytes

Ampicillin

Needle-shaped Best seen under polarized light

Indinavir

Starburst-shaped or individual needle-shaped crystals Best seen under polarized light

Sulfa

Needle-shaped; may cluster Best seen under polarized light

Urine concentration of crystal constituents pH Absence of crystallization inhibitors

Drugs are an underrecognized cause of crystals (see Table 3: Approach to the Genitourinary Patient: Drugs
That Cause Crystal Formation

).
Ca Oxalate Crystals

Cystine Crystals

Mg Ammonium Phosphate (Struvite) Crystals

Indinavir Crystals

Sulfa Crystals

Casts are made up of glycoprotein of unknown function (Tamm-Horsfall protein) secreted from the thick ascending loop of Henle. They are cylindrical and have regular margins. Their presence indicates renal origin, which may be helpful diagnostically. Types of casts differ in constituents and appearance (see Table 4: Approach to the Genitourinary Patient: Urinary Casts ).

Table 4

Urinary Casts
Type Description Significance

Plain casts Hyaline Glycoprotein matrix secreted by tubules Nonspecific Can be present in normal urine or in patients with low urine flow (eg, due to dehydration, after diuretic therapy), physiologic stress, an acute renal disorder plus other abnormalities, or a chronic renal disorder (as broad casts formed in dilated tubules) Present in advanced chronic kidney disease Predicts a poor prognosis

Waxy

Glycoprotein matrix with degraded protein Formed in atrophic tubules Highly refractile with waxy appearance Glycoprotein matrix with RBCs

Casts with inclusions RBC Virtually pathognomonic of

Often appears red-orange

glomerulonephritis Rarely occurs in patients with cortical necrosis or acute tubular injury or in runners with hematuria Occurs in acute tubular injury, glomerulonephritis, or nephrotic syndrome Suggests pyelonephritis but can indicate other causes of tubulointerstitial inflammation May occur in the exudative stage of proliferative glomerulonephritis

Epithelial cell

Protein matrix variably filled with tubular cells Protein matrix variably filled with WBCs

WBC

Granular

Glycoprotein matrix with protein or Occasionally occurs after exercise or cellular debris dehydration when renal function is normal More often indicates acute tubular necrosis Tubular cell or granular casts with pigment stain Fat droplets or oval fat bodies (cholesterol produces a Maltese cross pattern in polarized light) Hyaline cast with various cells (eg, RBCs, WBCs, tubular cells) Clumped urates, WBCs, bacteria, hair, glass fragments, cloth fiber, or artifacts Usually occurs in acute kidney injury due to hemolysis or rhabdomyolysis or in acute tubular necrosis May occur in various types of tubulointerstitial disorders In large numbers, strongly suggests nephrotic syndrome Usually occurs in proliferative glomerulonephritis Important not to confuse with true casts, which are cylindrical and shaped like renal tubules

Pigment

Fatty

Mixed Pseudocasts

Waxy and Granular Casts

RBC Cast

Epithelial Cell Cast

WBC Cast

Granular Casts

Fat (Lipid) Droplets

Fat Droplets-Maltese cross pattern

Hyaline Cast

Other urine tests: Other tests are useful in specific instances. Total protein excretion can be measured in a 24-h collection or can be estimated by the protein/creatinine ratio, which, in a random urine sample, correlates well with values in g/1.73 m BSA from a 24-h collection (eg, 400 mg/dL protein and 100 mg/dL creatinine in a random sample equal 4 g/1.73 m in a 24-h collection). The protein/creatinine ratio is less accurate when creatinine excretion is significantly increased (eg, in muscular athletes) or decreased (eg, in cachexia).
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Microalbuminuria is albumin excretion persistently between 30 and 300 mg/day (20 to 200 g/min); lesser amounts are considered within the range of normal, and amounts >300 mg/day (> 200 g/min) are considered overt proteinuria. Use of the urine albumin/urine creatinine ratio is a reliable and more convenient screening test because it avoids timed urine specimens and correlates well with 24-h values. A value > 30 mg/g (> 0.03 mg/mg) suggests microalbuminuria. The reliability of the test is best when a midmorning specimen is used, vigorous exercise is avoided before the test, and unusual creatinine production (in cachectic or very muscular patients) is not present. Microalbuminuria can occur in all of the following:
Diabetes mellitus

Hypertension Renal allograft dysfunction Preeclampsia UTI

Microalbuminuria is highly predictive of subsequent nephropathy in type 1 but not type 2 diabetes. Microalbuminuria is a risk factor for cardiovascular disorders and early cardiovascular mortality independent of diabetes or hypertension. Sulfosalicylic acid (SSA) test strips can be used to detect protein other than albumin (eg, Igs in multiple myeloma) when dipstick urine tests are negative; urine supernatant mixed with SSA becomes turbid if protein is present. The test is semiquantitative with a scale of 0 (no turbidity) to 4+(flocculent precipitates). Readings are falsely elevated by radiopaque contrast agents. Ketones spill into urine with ketonemia, but use of test strips to measure urinary ketones is no longer widely recommended because they measure only acetoacetic acid and acetone, not -hydroxybutyric acid. Thus, a false-negative result is possible even without an exogenous cause (eg, vitamin C, phenazopyridine

, N-acetylcysteine

); direct measurement of serum ketones is more accurate. Ketonuria is caused by endocrine and metabolic disorders and does not reflect renal dysfunction. Osmolality, the total number of solute particles per unit mass (mOsm/kg [mmol/kg]), can be measured directly by osmometer. Normally, osmolality is 50 to 1200 mOsm/kg. Measurement is most useful for evaluating hypernatremia, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and diabetes insipidus. Electrolyte measurements help diagnose specific disorders. Na level can help distinguish whether volume depletion (urine Na < 10 mEq/L) or acute tubular necrosis (urine Na > 40 mEq/L) is the cause of acute renal insufficiency or failure. The fractional excretion of Na (FENa) is the percentage of filtered Na that is excreted. It is calculated as the ratio of excreted to filtered Na, which can be simplified to the following:

where UNa is urine Na, PNa is plasma Na, PCr is plasma creatinine, and UCr is urine creatinine.

This ratio is a more reliable measure than UNa alone because UNa levels between 10 and 40 mEq/L are nonspecific. FENa < 1% suggests prerenal causes, such as volume depletion; however, acute glomerulonephritis or certain types of acute tubular necrosis (eg, rhabdomyolysis, radiocontrast-induced renal failure) can result in FENa < 1%. A value > 1% suggests acute tubular necrosis or acute interstitial nephritis. Other useful measurements include the following:
Fractional excretion of HCO3 in evaluation of renal tubular acidosis (see Renal Transport Abnormalities: Renal Tubular Acidosis (RTA)) Cl levels and urine anion gap for diagnosis of metabolic alkalosis (see Acid-Base Regulation and Disorders: Diagnosis) and nonanion gap metabolic acidosis (see Acid-Base Regulation and Disorders: Diagnosis) K levels in determining the cause of hypokalemia or hyperkalemia Levels of Ca, Mg, uric acid, oxalate, citrate, and cystine in evaluation of calculi

Eosinophils, cells that stain bright red or pink-white with Wright's or Hansel staining, most commonly indicate one of the following:
Acute interstitial nephritis Rapidly progressive glomerulonephritis Acute prostatitis Renal atheroembolism

Cytology is used for the following:

To screen for cancer in high-risk populations (eg, petrochemical workers) To evaluate painless hematuria in the absence of glomerular disease (suggested by the absence of dysmorphic RBCs, proteinuria, and renal failure) To check for recurrence after bladder tumor resection

Sensitivity is about 90% for carcinoma in situ; however, sensitivity is considerably lower for low-grade transitional cell carcinomas. Inflammatory or reactive hyperplastic lesions or cytotoxic drugs for carcinoma may produce false-positive results. Accuracy for detecting bladder tumors may be increased by vigorous bladder lavage with a small volume of 0.9% saline solution (50 mL pushed in and then aspirated by syringe through a catheter). Cells collected in the saline are concentrated and examined. Gram stain and cultures with susceptibility testing are indicated when GU tract infections are suspected; a positive result must be interpreted in the clinical context (see Urinary Tract Infections (UTI): Introduction). Amino acids are normally filtered and reabsorbed by the proximal tubules. They may appear in urine when a hereditary or acquired tubular transport defect (eg, Fanconi syndrome, cystinuria) is present. Measuring type and amount of amino acids may help in the diagnosis of certain types of calculi, renal tubular acidosis, and inherited disorders of metabolism.

Blood tests: Blood tests are useful in evaluation of renal disorders. Serum creatinine values > 1.3 mg/dL (> 114 mol/L) in men and > 1 mg/dL (> 90 mol/L) in women are usually abnormal. Serum creatinine depends on creatinine generation as well as renal creatinine excretion. Because creatinine turnover increases with higher muscle mass, muscular people have higher serum creatinine levels and elderly and undernourished people have lower levels. Serum creatinine may also be increased in the following conditions:
Use of ACE inhibitors and angiotensin II receptor blockers Consumption of large amounts of meat Use of some drugs (cimetidine , trimethoprim

, cefoxitin , flucytosine )

ACE inhibitors and angiotensin II receptor blockers reversibly decrease GFR and increase serum creatinine because they vasodilate efferent more than afferent glomerular arterioles, mainly in people who are dehydrated or are receiving diuretics. In general, serum creatinine alone is not a good indicator of kidney function. The Cockcroft and Gault formula and the Modification of Diet in Renal Disease formula estimate GFR based on serum creatinine and other parameters and more reliably evaluate kidney function. BUN/creatinine ratio is used to distinguish prerenal from renal or postrenal (obstructive) azotemia; a value > 15 is considered abnormal and may occur in prerenal and postrenal azotemia. However, BUN is affected by protein intake and by several nonrenal processes (eg, trauma, infection, GI bleeding, corticosteroids) and, although suggestive, is generally inconclusive as evidence of renal dysfunction. Cystatin C, a serine proteinase inhibitor that is produced by all nucleated cells and filtered by the kidneys, can also be used to evaluate kidney function. Its plasma concentration is independent of sex, age, and body weight. Testing is not always available, and values are not standardized across laboratories. Serum electrolytes (eg, Na, K, HCO3) may become abnormal and the anion gap (Na [Cl +HCO3]) may increase in acute kidney injury and chronic kidney disease. Serum electrolytes should be monitored periodically.

CBC may detect anemia in chronic kidney disease or, rarely, polycythemia in renal cell carcinoma or polycystic kidney disease. Anemia is often multifactorial (mainly due to erythropoietin deficiency and sometimes worsened or caused by blood loss in dialysis circuits or the GI tract); it may be microcytic or normocytic, and may be hypochromic or normochromic. Renin, a proteolytic enzyme, is stored in the juxtaglomerular cells of the kidneys. Renin secretion is stimulated by reduced blood volume and renal blood flow and is inhibited by Na and water retention. Plasma renin is assayed by measuring renin activity as the amount of angiotensin I generated per hour. Specimens should be drawn from well-hydrated, Na- and K-replete patients. Plasma renin, aldosterone, cortisol, and ACTH should be measured in evaluation of all of the following:
Adrenal insufficiency Hyperaldosteronism Refractory hypertension (see Hypertension: Renovascular Hypertension)

The plasma aldosterone/renin ratio calculated from measurements obtained with the patient in an upright posture is the best screening test for hyperaldosteronism, provided that plasma renin activity is > 0.5 ng/mL/h and aldosterone is > 12 to 15 ng/dL. Evaluating Kidney Function Kidney function is evaluated using values calculated from formulas based on results of blood and urine tests. GFR: Glomerular filtration rate (GFR), the volume of blood filtered through the kidney per minute, is the best overall measure of kidney function; it is expressed in mL/min. Because normal GFR increases with increasing body size, a correction factor using body surface area (BSA) typically is applied. This correction is necessary to compare a patient's GFR to normal and to define different stages of chronic kidney disease. Given the mean normal BSA of 1.73 m , the correction factor is 1.73/patient BSA; adjusted GFR results are then expressed as mL/min/1.73 m .
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Normal GFR in young, healthy adults is about 120 to 130 mL/min/1.73 m and declines with age to about 75 mL/min/1.73 m at age 70. Chronic kidney disease is defined by a GFR < 60 mL/min/1.73 m for > 3 mo. The gold standard for GFR measurement is inulin clearance. Inulin is neither absorbed nor secreted by the renal tubule and therefore it is the ideal marker for evaluation of kidney function. However, its measurement is cumbersome and therefore it is mostly used in research settings.
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Creatinine clearance: Creatinine is produced at a constant rate by muscle metabolism and is freely filtered by the glomeruli and also is secreted by the renal tubules. Because creatinine is secreted, creatinine clearance (CrCl) overestimates GFR by about 10 to 20% in people with normal kidney function and by up to 50% in patients with advanced renal failure; thus, use of CrCl to estimate GFR in chronic kidney disease is discouraged. Using a timed (usually 24-h) urine collection, CrCl can be calculated as

where UCr is urine creatinine in mg/mL, UVol is urine volume in mL/min of collection (1440 min for a full 24-h collection), and PCr is plasma creatinine in mg/mL. Estimating creatinine clearance: Because serum creatinine by itself is inadequate for evaluation of kidney function, several formulas have been devised to estimate CrCl using serum creatinine and other factors. The Cockcroft and Gault formula can be used to estimate CrCl. It uses age, lean body weight, and serum creatinine level. It is based on the premise that daily creatinine production is 28 mg/kg/day with a decrease of 0.2 mg/yr of age.