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© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (6): ITC6-1.
Terms of Use
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© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
in the clinic

Chronic Kidney
Disease

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Which patients are at increased risk for CKD?

 Risk factors
 Diabetes
 Hypertension
 Autoimmune diseases
 Systemic infections
 UTI, nephrolithiasis, lower urinary-tract obstruction
 Hyperuricemia
 Acute kidney injury
 Family history of chronic kidney disease

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
 Sociodemographic risk factors
 Older age
 Black race
 Smoking
 Heavy alcohol use
 Obesity
 NSAIDs

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Should clinicians screen patients for CKD?
If so, how?
 Screen individuals at increased risk for CKD
 Those older than 55 years
 Those with hypertension, diabetes, or obesity

 Screening: estimate GFR and test for kidney damage markers

 Serum creatinine to estimate GFR
 Urinalysis for leukocytes and red blood cells
 Qualitative test for urine albumin (or protein) with dipstick;
if positive, measure amount to calculate an albumin-to-
creatinine (or a protein-to-creatinine) ratio

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Urine albumin & protein to creatinine ratio
 Albumin-to-creatinine ratio
 Normal to mildly increased <30 mg/g
 Moderately increased 30-300 mg/g
 Severely increased >300 mg/g

 Protein-to-creatinine ratio
 Normal to mildly increased <150 mg/g
 Moderately increased 150-500 mg/g
 Severely increased >500 mg/g

 Type 2 diabetes: screen for albuminuria annually

 Positive when >30 mg/g creatinine in a spot urine sample

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Are preventive measures useful for
patients at increased risk for CKD?
 Diabetes
 Hyperglycemia is associated with development and
progression of diabetic nephropathy
 Good glycemic control reduces CKD risk
 Maintain hemoglobin A1c ~7% with dietary interventions,
oral hypoglycemic medications, and insulin

 Hypertension
 Hastens renal function decline
 Treatment reduces CV risks but not CKD risk
 Maintain blood pressure <140/90 mm Hg with lifestyle
modification and antihypertensive drug therapy

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
CLINICAL BOTTOM LINE: Screening
and Prevention...
 Who to screen
 Individuals > 55 years of age
 Individuals with hypertension or diabetes
 How to screen
 Estimate GFR from serum creatinine, and do a urinalysis
 In patients with diabetes
• Screen for proteinuria with urine albumin-to-creatinine
or protein-to-creatinine ratio
• Maintain strict glycemic control to prevent CKD

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What is the definition of CKD?
 Kidney damage or GFR <60 mL/min / 1.73 m2 for >3 mo
 Kidney damage can be either functional or structural
 Functional abnormalities
 Proteinuria, albuminuria
 Abnormalities of urinary sediment (dysmorphic red
cells)
 Structural abnormalities
 On ultrasound scanning or other radiological tests
 Polycystic kidney disease, reflux nephropathy, or other
abnormalities

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians estimate GFR and
the stage of CKD?
 MDRD equation
 GFR in mL/min per 1.73 m2
 GFR = 186.3 × (serum creatinine in mg/dL)−1.154 × age−0.203
× (1.210 if black) × (0.742 if female)

 CKD-EPI equation
 GFR = 141 × minimum(Scr/κ, 1)α × maximum(Scr/κ, 1)-1.209
× 0.993Age × (1.018 if female) × (1.159 if black)
 Scr is serum creatinine, κ is 0.7 for females and 0.9 for
males, α is -0.329 for females and -0.411 for males
 minimum indicates the minimum of Scr/κ or 1, maximum
indicates the maximum of Scr/κ or 1

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Stage of chronic kidney disease by GFR
and albuminuria categories.

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What clinical manifestations should clinicians
look for when evaluating patients for CKD?
 Findings associated with diabetes and hypertension
 History of HF or cirrhosis suggests decreased renal perfusion
 Infection with HBV, HCV, or HIV may cause proteinuria
 Family history of kidney disease suggests polycystic disease,
the Alport syndrome, or medullary cystic kidney disease
 Urinary problems may reflect underlying urinary tract disease
 Skin rash, arthritis, mononeuropathy, or systemic symptoms
suggests vasculitis, including lupus
 Recent diarrhea, bleeding, or dehydration may decrease renal
perfusion that leads to acute kidney injury
 A medication history may reveal a drug cause of CKD

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Physical Examination

 Check for orthostasis

 Look for rashes and petechiae
 Examine the fundus for diabetic retinopathy or
hypertensive retinopathy
 Evaluate for heart failure
 A renal bruit suggests renal artery stenosis
 Inflamed joints suggest vasculitis or autoimmune
processes
 Asterixis or encephalopathy suggests uremia

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What laboratory tests and imaging should
clinicians use to evaluate CKD?
 Serum creatinine (to estimate GFR)
 Serum electrolytes
 CBC and lipid profile
 Urinalysis (specific gravity, pH, red cells, leukocytes)
 If GFR <60 mL/min per 1.73 m2
 Serum calcium, phosphorus, parathyroid hormone,
albumin
 Renal ultrasound
 For hydronephrosis, cysts, and stones
 To assess echogenicity, size, kidney symmetry

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
 If indicated by findings
 Antinuclear antibody to evaluate for lupus
 Serologies for HBV, HCV, and HIV
 Serum antineutrophil cytoplasmic antibodies for vasculitis

 Serum and urine protein immunoelectrophoresis for

multiple myeloma

 Stages 4 and 5 CKD: test for hyperkalemia, acidosis,

hypocalcemia, hyperphosphatemia

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians classify CKD and
construct a differential diagnosis?
 By GFR and albuminuria
 Determine cause based on:
 Presence or absence of systemic disease
 Presumed location of damage in the kidney (glomerular,
tubulointerstitial, vascular, or cystic)

 Classify patients with CKD into 1 of 3 broad categories:

 Diabetic kidney disease
 Hypertensive kidney disease
 Non-hypertensive, non-diabetic kidney disease

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider
consulting with a nephrologist for
diagnosing patients with possible CKD?

 Persistent albumin-to-creatinine ratio ≥300mg/g

 Nephritic syndrome (hematuria, proteinuria, and
hypertension)
 Sustained hematuria (red cell casts or RBC > 20/high
power field)
 No clear etiology of CKD
 Type 2 diabetes with proteinuria w/o coexistent
retinopathy or neuropathy
 Rapid decline in kidney function (>5 mL/min per 1.73 m2
per year)

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
CLINICAL BOTTOM LINE: Diagnosis...
 CKD is defined as kidney damage or a GFR <60 mL/min per
1.73 m2 for > 3 months
 Classify
 Diabetic nephropathy
 Hypertensive nephropathy
 Nondiabetic, nonhypertensive kidney disease
 Then, into groups based on levels of GFR and albuminuria
 History and physical exam often point to a cause
 Definitive diagnosis requires:
 Diagnostic tests
 Renal ultrasound
 Sometimes renal biopsy

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What non-drug therapies should clinicians
recommend?
 Quit smoking, and exercise 30 min/d on most days
 Limit alcohol intake
 Maintain BMI within normal range
 Eat a diet high in fruits, vegetables, and whole grains
 DASH diet recommended if GFR >60 mL/min per 1.73 m2
and high normal blood pressure or stage 1 hypertension
 If hypertension present: restrict salt intake <2.0 g/d
 Most patients with CKD should avoid high-protein diets
 Stage 4 or 5: consider low-protein diet (0.6 g/kg/d)

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
Which drugs and other agents cause acute
kidney injury in patients with CKD?
 Nephrotoxic medications
 Aminoglycoside antibiotics, amphotericin B, NSAIDS,
radiocontrast agents
 If radiocontrast agents essential: give sodium bicarbonate
or 0.9% normal saline IV before and after procedure for
patients at increased risk for contrast nephropathy
 Consider N-acetylcysteine before and after radiocontrast
only in high-risk patients
 Avoid high doses of gadolinium contrast in stages 4 and 5
due to risk for nephrogenic systemic fibrosis

 Adjust dosing of other medications to avoid other AEs

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What is the role of blood pressure
management?
 To reduce CVD risk, treat to <140/90 mm Hg
 If proteinuria is significant or urine albumin-to-creatinine
ratio >30mg/g: treat to <130/80 mm Hg
 Use ACE inhibitors and ARBs (improve kidney outcomes)

 Combination therapy often needed

 Diuretics reduce extracellular fluid volume, lower BP, and
reduce risk for CVD
 Diuretics also potentiate effects of antihypertensives
 Thiazide-type diuretic if GFR ≥30 mL/min per 1.73 m2

 Loop diuretic if GFR <30 mL/min per 1.73 m2

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
When should clinicians prescribe ACE
inhibitors versus ARBs?

 Prescribe either for reducing progression of diabetic

nephropathy
 Prescribe either in hypertension or in diabetes when urine
albumin excretion >30mg / 24h
 Prescribe either in non-diabetic proteinuria
 Do not combine an ACE inhibitor with an ARB
 Monitor patients closely for side effects and adjust dose
as needed
 Safe to continue medication if GFR declines < 30% over 4
mos and serum potassium <5.5 mEq/L

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What is the role of glycemic control in
patients with diabetes and CKD?
 Good glycemic control reduces:
 Progression of CKD
 Incidence proteinuria
 Maybe end-stage renal disease

 However, CKD increases risk for hypoglycemia

 Current CKD guidelines recommend a goal A1c level ~7%
 Avoid using metformin if GFR <30 mL/min per 1.73 m2

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians manage metabolic
complications?
 Vitamin D and phosphorous metabolism
 Derangements occur if GFR <30-40 mL/min per 1.73 m2
 Use dietary phosphorous restriction, phosphate binders,
and vitamin D supplementation
 Hyperkalemia
 Dangerous elevations occur mostly only in stages 4 / 5
 Use dietary potassium restriction, and if necessary, sodium
polystyrene sulfonate
 Hyperkalemia >6mEq/L or hyperkalemic EKG change
requires emergency treatment with IV calcium gluconate,
glucose, insulin, bicarbonate (if acidosis present), and
sodium polystyrene sulfonate
 If these measure fail, hemodialysis may be needed

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
 Metabolic acidosis
 Seldom significant until GFR <30 mL/min per 1.73 m2
 Contributes to CKD progression, insulin resistance,
decreased cardiorespiratory fitness, altered bone
metabolism
 Use alkali therapy with serum bicarbonate <22 mmol/L to
maintain serum bicarbonate levels within normal range

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians manage patients
with anemia?
 Measure hemoglobin and hematocrit, RBC indices,
reticulocyte count, serum iron, percent transferrin
saturation, vitamin B12 and folate levels, serum ferritin
 Identify potential sources of bleeding
 Treat with erythropoietin when hemoglobin drops below
9-10 g/dL
 Prescribe oral / IV iron as needed to maintain iron stores
 Maintain hemoglobin levels <11.5 g/dL
 Use caution with active malignancy or history of stroke

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians treat cardiovascular
risk factors?
 Aggressively reduce risk factors for atherosclerosis
 Encourage a healthy lifestyle regarding smoking, exercise,
alcohol intake, and BMI

 Assess for other cardiovascular risk factors

 Check BP, and treat hypertension
 Screen for diabetes, and treat elevated blood glucose
 For people with CKD, ACC/AHA guidelines recommend
treatment with statin or statin/ezetimibe combination
regardless of cholesterol level

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
How should clinicians monitor patients
with CKD?
 Once a year check BP; GFR; hemoglobin level; and serum
potassium, calcium, phosphorous, PTH, and albumin

 More frequent monitoring may be needed if

 CKD is moderate to severe
 History of rapid decline in kidney function
 There are risk factors for faster progression (smoking,
poorly controlled hypertension or diabetes, proteinuria)
 Exposure to a cause of acute kidney injury
 Active or changing therapeutic interventions to treat CKD,
hypertension, or proteinuria

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
What are the indications for renal
replacement therapy?
 Volume overload unresponsive to diuretics
 Pericarditis
 Uremic encephalopathy
 Major bleeding secondary to uremic platelets
 Hypertension that does not respond to treatment
 Hyperkalemia and metabolic acidosis that cannot be
managed medically
 Progressive “uremic” symptoms, which include fatigue;
anorexia, nausea or vomiting; malnutrition; and insomnia

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
When should clinicians consider consulting a
nephrologist for treating patients with CKD?
 To manage complications of advanced CKD
 For assistance with a care plan for advanced or complex
renal disease
 For therapeutic decision-making about complex acute or
chronic glomerular and tubulointerstitial diseases
 When dialysis is anticipated
 When GFR first falls below 30 mL/min per 1.73 m2
 To discuss treatment for end-stage renal disease
 For counseling, psychoeducational interventions, and
referral for fistula placement

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.
CLINICAL BOTTOM LINE: Treatment...
 The goals are to slow progression of CKD and prevent
complications from cardiovascular disease
 Maintain normal blood pressure in patients with hypertension
 Include an ACE inhibitor or an ARB when treating
hypertension
 Control glycemia in patients with diabetes
 Manage electrolyte disturbances, anemia, secondary
hyperparathyroidism, and malnutrition
 Refer to a nephrologist as CKD progresses

© Copyright Annals of Internal Medicine, 2015

Ann Int Med. 162 (6): ITC6-1.