KIMMELSTIEL WILSON SYNDROME GENERAL OBJECTIVE To comprehensively understand Kimmelstiel-Wilson Syndrome. Specific Objectives To correlate the patients overall history with the disease process. To identify pertinent physical examination results evident in the patient. To analyze the laboratory and diagnostic studies which will justify the diagnosis. To review the anatomy and physiology of the systems involved. To thoroughly explain the pathophysiology of the disorder including risk factors and clinical manifestations. 6. To evaluate the nursing and medical management rendered to the patient through the Nursing Care Plan. 7. To discuss the prognosis of the patient and the recommendations to combat or decelerate the progression of the disease. INTRODUCTION 1. 2. 3. 4. 5. History Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel- Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and nodular glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime cause for dialysis in many Western countries. Discovered by British physician Clifford Wilson (1906-1997) and Germanborn American physician Paul Kimmelstiel (1900-1970) and was published for the first time in 1936. Causes The exact cause of diabetic nephropathy is unknown, but it is believed that uncontrolled high blood sugar leads to the development of kidney damage. In some cases, your genes or family history may also play a role. Not all persons with diabetes develop this condition. Each kidney is made of hundreds of thousands of filtering units called nephrons. Each nephron has a cluster of tiny blood vessels called a glomerulus. Together these structures help remove waste from the body. Too much blood sugar can damage these structures, causing them to thicken and become scarred. Slowly, over time, more and more blood vessels are destroyed. The kidney structures begin to leak and protein (albumin) begins to pass into the urine. Persons with diabetes who have the following risk factors are more likely to develop this condition: African American, Hispanic, American Indian or Asian origin Family history of kidney disease or high blood pressure, poor control of blood pressure, poor control of blood sugars, Type 1 diabetes before age 20, smoking. Diabetic nephropathy generally goes along with other diabetes complications including high blood pressure, retinopathy, and blood vessel changes. Prevalence and Incidence Rate Diabetes has become the primary cause of end-stage renal disease (ESRD), and the incidence of type 2 diabetes mellitus continues to grow worldwide. Approximately 44% of new patients entering dialysis are diabetics. Early diagnosis of diabetes and early intervention are critical in preventing the normal progression to renal failure seen in many type 1 and a significant percentage of type 2 diabetics. The prevalence of diabetes is higher in certain racial and ethnic groups, affecting approximately 13% of African Americans, 9.5% of Hispanics, 15% of Native Americans and 15% of Asians, primarily with type 2 diabetes. Approximately 20% to 30% of all diabetics will develop evidence of nephropathy, although a higher percentage of type 1 patients progress to ESRD. Epidemiology The syndrome can be seen in patients with chronic diabetes (15 years or more after onset), so patients are usually of older age (between 50 and 70 years old). The disease is progressive and may cause death two or three years after the initial lesions, and is more frequent in men. Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease. People with both type 1 and type 2 diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. Further, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure. Also people with high cholesterol level in their blood have much more risk than others. Signs & Symptoms Early signs and symptoms of kidney disease in patients with diabetes are typically unusual. However, a vast array of signs and symptoms listed may manifest when kidney disease has progressed: Swelling, usually around the eyes in the mornings; later, general body swelling may result, such as swelling of the legs; Foamy appearance or excessive frothing of the urine; Unintentional weight gain (from fluid accumulation); Fatigue; Frequent hiccups; General ill feeling; Generalized itching; Headache; Nausea and vomiting; Poor appetite; Weakness, paleness, and anemia; Ankle and leg swelling, leg cramps; Going to the bathroom more often at night High blood pressure Tests and diagnosis Laboratory tests that may be done include: BUN (Blood Urea Nitrogen) Serum creatinine The levels of these tests will increase as kidney damage gets worse. Other laboratory tests that may be done include: 24-hour urine protein Blood levels of phosphorus, calcium, bicarbonate, and potassium Hemoglobin Hematocrit Protein electrophoresis - urine Red blood cell (RBC) count. Complications Possible complications include: hypoglycemia (from decreased excretion of insulin) rapidly progressing chronic kidney failure, end-stage kidney disease, hyperkalemia, severe hypertension, complications of hemodialysis, complications of kidney transplant, coexistence of other diabetes complications, peritonitis (if peritoneal dialysis used), increased infections. About 20% of clients with type II are found to have diabetes nephropathy 5-10 yrs after diagnosis. A consequence of microangiopathy, nephropathy involves damage to and eventual obliteration of the capillaries that supply the glomeruli of the kidney. This damage leads in turn to a complex a pathologic changes and manifestations which includes intercapillary glomerulosclerosis, nephrosis, gross albuminuria and hypertension. Risk factors include poor glycemic control, duration of disease and hypertension. With worsening of the nephrosis, chronic renal failure ensues. Unless the client can be maintained with hemodialysis or receives a renal transplant, uremia eventually causes death. Diabetic nephropathy cannot be cured. However prompt and adequate intervention for renal and bladder infection can prevent these causes of renal failure. Unsuccessfully treated nephropathy progresses to end stage renal disease. Treatment at this point includes hemodialysis, peritoneal dialysis or kidney transplantation. Treatments and drugs
Childhood Illnesses: Measles, mumps, chickenpox. Allergies: Patient had no known allergies. Alcohol: Patient drinks 1-2 medium-sized glasses of tuba once every month. Smoking: Patient is a non-smoker. Family History Patient love is the 8th child among 10 siblings. To date, only 3 of them are still alive. Her father was hypertensive and died with unknown cause. Her mother was diagnosed to have DM type II. Four of her siblings were known diabetics which were not properly managed. All of her siblings were hypertensive. Heredofamilial Diseases: Paternal Side: (+) Hypertension, DM Maternal Side: (+) Hypertension, DM, Bronchial asthma Personal/Psychosocial History Patient Love was born and raised in Balangiga, Eastern Samar. She is an elementary graduate. She got married at age 22 to a PUJ driver from Tacloban and since their marriage, they have resided in the city already. They were blessed with four children, 2 boys and 2 girls all of whom have families of their own already. Her husband passed away in 2006 at the age of 56 due to a heart attack. Patient love is a housewife and has a small sari-sari store which helps augment the familys income. At present, her youngest daughter and her family lives with Patient love. Activities: Typical day: Arises at 5 AM, prepares breakfast, cleans the house, tends her store, watches over 2 grandchildren, prepares lunch, takes afternoon naps, gardens, prepares dinner, watches TV, sleeps at 8 PM. Diet: Eats 3 times per day and usual diet consists of 2 cups of rice, fish, sometimes meat, vegetables and 8 glasses of water in one day. Before diagnosed to have diabetes, she consumes 500ml of Coke everyday and is fond of eating sweets such as kalamay on fried banana or camote. She puts a minimum of 2 tbsp of sugar in her coffee everyday. Her day was
Nails: Inspection Palpation Hair: Inspection Head: Inspection Eyes: Inspection Normocephalic No lesions, masses, injury, scars, lumps, scaling Symmetric facial features with no weakness, no involuntary movements observed. Black and white, evenly distributed hair. No lice, no nits. Smooth with convex curvature Pale With a slight delay in capillary refill >3 seconds. Dirty untrimmed nails No clubbing of fingers.
Palpation
Symmetrical, equal sized auricles. Color is the same with facial skin. Auricle aligned to outer canthus of the eye. Tympanic membrane pearly gray, landmarks intact, no perforation. No hemorrhage, crusting or swelling. Cerumen noted on ear canals. Pinna has no mass, swelling, scaling, discharge.
Spine and back: No lumps nor tenderness. Mobile and firm, pinna recoil after it is folded. Inspection Palpation Normal spinal profile. Vertebral column no tenderness, no deformity or curvature. No lateral spine deviation, no scoliosis, kyphosis, lordosis noted.
Nose:
Inspection
Palpation
Pale nasal mucosa. Uniform with facial color. Nares patent. Nasal septum intact and at midline. Nose bridge not deviated. No perforation noted. No nasal discharges, no hemorrhage noted.
Thorax and Lungs: No sinus tenderness. No lesions, no lumps or masses palpated. Inspection Palpation Symmetric chest expansion.
Mouth:
Inspection
Extremities: Inspection Palpation Have minimal ROM Unable to maintain flexion against resistance. (Muscle strength: 3/5) All peripheral pulses present, 2+ and = bilaterally. No calf tenderness noted. Tan in color, no active lesions noted. With Grade 2 pitting bipedal edema. Sole and nails are pale.
Palpation
Generally unequal in size. Uniform skin color and intact. Rounded, everted, equal in size and areola is dark brown in color, and points to the same direction without discharges. Generally symmetric; no retractions or dimpling, no rashes, active lesions or discharge. No active lesions noted.
Neurologic: Alert and oriented to person, place, time. Appearance, behavior, speech is appropriate. Remote and recent memories intact. Cranial nerves II through XII intact. Sensory: pinprick, light touch, vibration intact. Stereognosis, able to identify key.
Heart:
Soft and smooth. Contour and consistency firm and homogenous. No tenderness, masses or nodules noted.
REVIEW OF SYSTEMS GENERAL SURVEY: Patient is pale and weak. Integumentary: HEENT: Pale. Dry skin with Senile skin turgor. With edema No history of skin disease. No itchiness, no active skin lesions.
Auscultation PMI in 5th left ICS at the midclavicular line; no thrills. No extra murmurs heard.
Abdomen: Inspection Skin with no scars or any active lesions. No visible veins. Auscultation Normoactive bowel sounds 16 per minute. No bruits heard. Percussion
Peripheral Vascular: With Grade 2 pitting bipedal edema. No varicosities. No leg cramps.
Musculoskeletal: With muscle weakness (Muscle strength: 3/5) With limitation of movement No joint pain, stiffness, muscle pain. No deformities.
Respiratory: Eupneic.
Gastrointestinal: Neurologic: No vomiting. No diarrhea. Moves bowel everyday to a formed brown-colored stool. No pain nor rectal bleeding. No heartburn, no indigestion, no abdominal pain. No problems with coordination, difficulty speaking. No memory problems.
Genitourinary:
1.7 8.3 mmol/L 80 120 mg/dl 140 360 mol/L 135 145 mEq/L 3.5 5 mEq/L
Sodium
126.9
Potassium
5.7
24-Hour Urine Collection: January 8, 2010 Normal 24-hour urine total volume Urine creatinine 800 1800 mL
Result 2800
Significance : polyuria
Urinalysis: January 7, 2010 Normal Glucose Albumin Negative Negative Result Trace ++ Significance High blood glucose level Albuminuria, may indicate damage to kidneys normal Presence of crystals, RBCs, epithelial cells. normal normal normal : indicates tubular damage/ injury to the kidneys. : Proteinuria normal
182
: creatinine is reabsorbed in kidney damage : inability to excrete creatinine in kidney damage :increased protein excretion in impaired kidney function
87 107 mL/min
48
150 mg/24hours
300
DIAGNOSTIC STUDIES X-Ray: January 7, 2010 X-Ray Report: Impression: No significant chest findings.
RBC Bacteria
0 1/hpf Few
3/hpf Few
Elevated blood levels of amino acids, as would be seen after consumption of a protein-rich meal: In this situation, glucagon would foster conversion of excess amino acids to glucose by enhancing gluconeogenesis. Since high blood levels of amino acids also stimulate insulin release, this would be a situation in which both insulin and glucagon are active. Exercise: In this case, it is not clear whether the actual stimulus is exercise per se, or the accompanying exercise-induced depletion of glucose.
Pancreatic islets house three major cell types, each of which produces a different endocrine product:
B. Insulin Structure of Insulin Insulin is a rather small protein, with a molecular weight of about 6000 Daltons. It is composed of two chains held together by disulfide bonds. Biosynthesis of Insulin Insulin is synthesized in significant quantities only in beta cells in the pancreas. The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm. When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity. Control of Insulin Secretion
Alpha cells (A cells) secrete the hormone glucagon. Beta cells (B cells) produce insulin and are the most abundant of the islet cells. Delta cells (D cells) secrete the hormone somatostatin, which is also produced by a number of other endocrine cells in the body.
A. Glucagon major role in maintaining normal concentrations of glucose in blood has the effect of increasing blood glucose levels. linear peptide of 29 amino acids. Glucagon is synthesized as proglucagon and proteolytically processed to yield glucagon within alpha cells of the pancreatic islets. Proglucagon is also expressed within the intestinal tract, where it is processed not into glucagon, but to a family of glucagon-like peptides (enteroglucagon). Physiologic Effects of Glucagon Glucagon exerts control over two pivotal metabolic pathways within the liver, leading that organ to dispense glucose to the rest of the body:
Glucagon stimulates breakdown of glycogen stored in the liver. When blood glucose levels are high, large amounts of glucose are taken up by the liver. Under the influence of insulin, much of this glucose is stored in the form of glycogen. Later, when blood glucose levels begin to fall, glucagon is secreted and acts on hepatocytes to activate the enzymes that depolymerize glycogen and release glucose. Glucagon activates hepatic gluconeogenesis. Gluconeogenesis is the pathway by which non-hexose substrates such as amino acids are converted to glucose. As such, it provides another source of glucose for blood. This is especially important in animals like cats and sheep that don't absorb much if any glucose from the intestine - in these species, activation of gluconeogenic enzymes is the chief mechanism by which glucagon does its job.
Glucose is transported into the beta cell by facilitated diffusion through a glucose transporter; elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the beta cell. Elevated concentrations of glucose within the beta cell ultimately leads to membrane depolarization and an influx of extracellular calcium. The resulting increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules. The mechanisms by which elevated glucose
C. Somatostatin first discovered in hypothalamic extracts and identified as a hormone that inhibited secretion of growth hormone.
II. Anatomy of the Renal System Both forms of somatostatin are generated by proteolytic cleavage of prosomatostatin, which itself is derived from preprosomatostatin. Two cysteine residules in SS-14 allow the peptide to form an internal disulfide bond. Physiologic Effects "somatostatin inhibits the secretion of many other hormones". Effects on the Pituitary Gland Somatostatin was named for its effect of inhibiting secretion of growth hormone from the pituitary gland. Effects on the Pancreas Somatostatin appears to act primarily in a paracrine manner to inhibit the secretion of both insulin and glucagon. It also has the effect in suppressing pancreatic exocrine secretions, by inhibiting cholecystokinin-stimulated enzyme secretion and secretin-stimulated bicarbonate secretion. Effects on the Gastrointestinal Tract It has been shown to inhibit secretion of many of the other GI hormones, including gastrin, cholecystokinin, secretin and vasoactive intestinal peptide. Somatostatin suppresses secretion 1. Kidney A. Pair of Organs a. Bean-Shaped--Most Species b. Heart-Shaped--Horses c. Lobulated--Cattle B. Retroperitoneal a. Located outside of abdominal cavity suspended by peritoneum C. Blood Supply a. Renal Artery i. Brings blood to Kidney ii. Arises directly from aorta b. Renal Vein i. Brings blood away from Kidney ii. Empties into the Caudal Vena Cava D. Divisions a. Cortex i. Outer Portion ii. Contains upper parts of nephrons --Glomeruli and Tubules b. Medulla i. Inner Portion ii. Contains lower parts of nephrons --Loops of Henle and Collecting Ducts c. Renal Pelvis i. Drains kidney and connects ureters d. Renal Hilus
RECOMMENDATION The principles of prevention and treatment of Kimmelstiel-Wilson Syndrome are the same. However, the role of each factor could be different in each stage of disease. It is important to define the stage that is the target of intervention (microalbuminuria, proteinuria or GFR) and the outcome of interest. Two recent meta-analyses have demonstrated different results when evaluating different outcomes, such as proteinuria, GFR decline or progression to ESRD. Probably the best treatment is a multiple risk factor interventional approach, but due to a practical point of view each aspect will be addressed individually. The goal to be pursued is retarding the development or progression of DN and to decrease the patients cardiovascular risk and mortality. 1. Keep blood glucose levels as close to normal as possible. The American Diabetes Association recommends that you keep your blood sugar levels at: 90 mg/dL to 130 mg/dL before meals 110 mg/dL to 150 mg/dL at bedtime. Less than 180 mg/dL 1 to 2 hours after meals.
2. Maintain blood pressure at less than 130/80 mm Hg with medicine, diet, and exercise. 3. Follow the nutrition guidelines Eating fewer processed foods, such as snack items, luncheon meats, and canned soups, will reduce the amount of sodium in your diet. A diet high in calcium, potassium, and magnesium may lower your blood pressure. A diet high in sodium may cause high blood pressure. To increase the potassium in your diet, fruits and vegetables are excellent sources of this nutrient. Dairy products are high in calcium and magnesium. DASH recommends that you eat 8 to 10 servings of fruits and vegetables and 3 servings of low-fat dairy products each day. Eating a diet low in both saturated fat and total fat will also help lower your blood pressure. Only 30% of your total calories should be from fat, with only 7% to 10% of your fat calories from saturated fat. Saturated fat is found in meats, cheeses, butter, poultry, snack foods, and other processed foods. In general, vegetarian diets reduce blood pressure. The DASH diet could easily be a vegetarian diet if legumes were substituted for meat. Vegetarian diets tend to be higher in potassium, magnesium, and calcium, as is the DASH diet. Vegetarian diets also are higher in fiber and unsaturated fat than other diets. 4. Do not smoke or use other tobacco products. 5. Avoid dehydration by promptly treating other conditionssuch as diarrhea, vomiting, or feverthat can cause it. 6. Treat other conditions that may block the normal flow of urine out of the kidneys, such as kidney stones, an enlarged prostate, or bladder problems. 7. Avoid the use of unprescribed medicines that may be harmful to our kidneys, especially nonsteroidal anti-inflammatory drugs (NSAIDs).
Kimmelstiel-Wilson Syndrome is a chronic complication of DM with a growing incidence. Therefore it is essential to have a better understanding of it, especially in relation to prevention and aggressive management to avoid progression to ESRD. Besides, its direct association with cardiovascular complications makes it imperative to perform intensive, early management of the risk factors. The study of DN has evolved a lot as regards its pathophysiology, stages of renal involvement and, especially, the therapeutic instruments available. Early detection of DN, and the multi-factorial approach targeting the main risk factors may delay progression of kidney disease in DM.