MKSAP 17 - Nephrology by American College of Physicians

MKSAP® 17

Medical Knowledge Self-Assessment Program®

Nephrology

150591010 150591010

19 AMA PRA Category 1 Credits™ available until December 31, 2018.

Table of Contents Clinical Evaluation of Kidney Function Assessment of Kidney Function . . . . . . . . . . . . . . . . . . . . . 1 Biochemical Markers of Kidney Function . . . . . . . . . 1 Estimation of Glomerular Filtration Rate. . . . . . . . . . 3 Interpretation of the Urinalysis. . . . . . . . . . . . . . . . . . . . . . 3 Urine Dipstick or Automated Urinalysis. . . . . . . . . . . 3 Urine Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Measurement of Albumin and Protein Excretion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Clinical Evaluation of Hematuria. . . . . . . . . . . . . . . . 7 Imaging Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Kidney Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Fluids and Electrolytes Osmolality and Tonicity. . . . . . . . . . . . . . . . . . . . . . . . . . . Disorders of Serum Sodium. . . . . . . . . . . . . . . . . . . . . . . . Hyponatremia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hypernatremia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Disorders of Serum Potassium . . . . . . . . . . . . . . . . . . . . . Hypokalemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hyperkalemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Disorders of Serum Phosphate . . . . . . . . . . . . . . . . . . . . . Hypophosphatemia. . . . . . . . . . . . . . . . . . . . . . . . . . . Hyperphosphatemia. . . . . . . . . . . . . . . . . . . . . . . . . .

10 10 10 13 14 14 16 18 18 19

Acid-Base Disorders Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Metabolic Acidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 General Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Increased Anion Gap Metabolic Acidosis. . . . . . . . . 21 Normal Anion Gap Metabolic Acidosis. . . . . . . . . . . 23 Acidosis in Acute and Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Metabolic Alkalosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Respiratory Acidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Respiratory Alkalosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Hypertension Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Consequences of Sustained Hypertension. . . . . . . . . . . . 28 End-Organ Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Clinical Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Blood Pressure Measurement . . . . . . . . . . . . . . . . . . . . . . 29

Proper Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Manual (Auscultatory) Blood Pressure Monitoring. . . . . . . . . . . . . . . . . . . . . . . . . . 29 Electronic Blood Pressure Monitoring . . . . . . . . . . . 29 Ambulatory Blood Pressure Monitoring. . . . . . . . . . 29 Home Blood Pressure Monitoring. . . . . . . . . . . . . . . 29 Evaluation of the Patient with Newly Diagnosed Hypertension . . . . . . . . . . . . . . . . . . . 30 History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Physical Examination. . . . . . . . . . . . . . . . . . . . . . . . . 31 Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Classification of Hypertension. . . . . . . . . . . . . . . . . . . . . . 32 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Prehypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Stage 1 and 2 Hypertension . . . . . . . . . . . . . . . . . . . . 32 Primary Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Genetic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Societal Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 White Coat Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . 36 Masked Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Resistant Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Secondary Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Renovascular Hypertension. . . . . . . . . . . . . . . . . . . . 38 Hypokalemia and Hypertension. . . . . . . . . . . . . . . . 38 Pheochromocytoma. . . . . . . . . . . . . . . . . . . . . . . . . 39 Special Populations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Women. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Patients with Diabetes Mellitus. . . . . . . . . . . . . . . . 39 Black Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Older Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Chronic Tubulointerstitial Diseases Pathophysiology and Epidemiology . . . . . . . . . . . . . . . . 40 Diagnosis and Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . 40 Causes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Immunologic Diseases. . . . . . . . . . . . . . . . . . . . . . . . 41 Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Malignancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Medications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

viii

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Hyperuricemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Obstruction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Glomerular Diseases Pathophysiology and Epidemiology . . . . . . . . . . . . . . . . . 43 Clinical Manifestations of Glomerular Disease . . . . . . . 44 The Nephrotic Syndrome. . . . . . . . . . . . . . . . . . . . . 44 The Nephritic Syndrome . . . . . . . . . . . . . . . . . . . . . . 45 Conditions Associated With the Nephrotic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Focal Segmental Glomerulosclerosis. . . . . . . . . . . . . 45 Membranous Glomerulopathy. . . . . . . . . . . . . . . . . 46 Minimal Change Glomerulopathy. . . . . . . . . . . . . . . 47 Diabetic Nephropathy. . . . . . . . . . . . . . . . . . . . . . . . . 47 Conditions Associated With the Nephritic Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 Rapidly Progressive Glomerulonephritis . . . . . . . . 48 Anti–Glomerular Basement Membrane Antibody Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Pauci-Immune Glomerulonephritis. . . . . . . . . . . . 49 Immune Complex–Mediated Glomerulonephritis. . 50 Collagen Type IV–Related Nephropathies. . . . . . . . . 53

Kidney Manifestations of Gammopathies Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Amyloidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Monoclonal Immunoglobulin Deposition Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Multiple Myeloma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Cryoglobulinemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Fibrillary and Immunotactoid Glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

Genetic Disorders and Kidney Disease Cystic Kidney Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Autosomal Dominant Polycystic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Tuberous Sclerosis Complex . . . . . . . . . . . . . . . . . . 56 Noncystic Kidney Disorders. . . . . . . . . . . . . . . . . . . . . . . 56 Collagen Type IV–Related Nephropathies. . . . . . . . 56 Fabry Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Acute Kidney Injury Pathophysiology and Epidemiology . . . . . . . . . . . . . . . . . 58 Definition and Classification. . . . . . . . . . . . . . . . . . . . . . . 58 Clinical Manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Causes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Prerenal Acute Kidney Injury . . . . . . . . . . . . . . . . . . 61

Intrinsic Kidney Diseases. . . . . . . . . . . . . . . . . . . . . . 61 Postrenal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Acute Kidney Injury in Specific Clinical Settings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Contrast-Induced Nephropathy. . . . . . . . . . . . . . . . 65 Cardiorenal Syndrome. . . . . . . . . . . . . . . . . . . . . . . 65 Hepatorenal Syndrome. . . . . . . . . . . . . . . . . . . . . . . 66 Tumor Lysis Syndrome. . . . . . . . . . . . . . . . . . . . . . . 66 Abdominal Compartment Syndrome. . . . . . . . . . . 66 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 General Considerations. . . . . . . . . . . . . . . . . . . . . . . 66 Acute Dialysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Kidney Stones Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Clinical Manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Types of Kidney Stones. . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Calcium Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Struvite Stones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Uric Acid Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Cystine Stones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Acute Management. . . . . . . . . . . . . . . . . . . . . . . . . . 69 Urologic Management. . . . . . . . . . . . . . . . . . . . . . . . 69 Risk Factor Evaluation and Prevention Strategies . . . . . . . . . . . . . . . . . . . . . . . . . 71

The Kidney in Pregnancy Normal Physiologic Changes in Pregnancy . . . . . . . . . . . 71 Changes in Hemodynamics. . . . . . . . . . . . . . . . . . . . 71 Changes in the Urinary Tract. . . . . . . . . . . . . . . . . . . 71 Changes in Acid-Base Regulation . . . . . . . . . . . . . . . 71 Changes in Water Homeostasis . . . . . . . . . . . . . . . . . 71 Hypertension in Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . 71 Chronic Hypertension . . . . . . . . . . . . . . . . . . . . . . . . 71 Gestational Hypertension. . . . . . . . . . . . . . . . . . . . . . 72 Preeclampsia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Chronic Kidney Disease in Pregnancy. . . . . . . . . . . . . . . 73

Chronic Kidney Disease Definition and Staging. . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Pathophysiology and Epidemiology . . . . . . . . . . . . . . . . . 75 Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Clinical Manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Complications and Management. . . . . . . . . . . . . . . . . . . . 75 Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . . . 75 Chronic Kidney Disease-Mineral and Bone Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . 76

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Anemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Metabolic Acidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Nephrotoxins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Proteinuria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Protein Restriction . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Special Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Vaccination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Vascular Access. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Older Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

End-Stage Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . 80 Dialysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Kidney Transplantation . . . . . . . . . . . . . . . . . . . . . . . 82 Complications of End-Stage Kidney Disease. . . . . 84

Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Self-Assessment Test. . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

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Nephrology Clinical Evaluation of Kidney Function Assessment of Kidney Function Glomerular filtration rate (GFR) is the net sum of the filtration rates of thousands of nephrons, providing a quantitative measure of the flow rate of filtered fluid through the kidney per minute. Normal GFR is influenced by gender and body size, with a steady decline with aging. Assessment of GFR in patients with kidney disease provides an index of the severity of kidney functional impairment. There is not an exact correlation between the loss of functioning nephrons and GFR due to compensatory hypertrophy and increased flow in residual nephrons. Consequently, patients may have significant structural kidney disease with a normal GFR and/or progression of structural kidney disease without a significant change in measured GFR.

Biochemical Markers of Kidney Function Serum creatinine is generated from the metabolism of creatine in muscle and from dietary meat. It is freely filtered by the glomerulus without metabolism or reabsorption by renal tubules. Although some creatinine is secreted by organic cation transport mechanisms in the proximal tubule, it is useful as an endogenous marker of GFR. Measurement of serum creatinine concentration has been used for almost a century as an indicator of kidney function. Although it is the most commonly used marker of GFR, it is an imperfect measure. The relationship between GFR and serum creatinine is not linear, but inversely proportional (Figure 1). In patients who become functionally anephric, the serum creatinine typically increases 1.0 to 1.5 mg/dL (88.4133 µmol/L) per day. Reduction of muscle mass, as seen in amputees and those with malnutrition or muscle wasting, can result in a lower serum creatinine concentration without a change in GFR. Because of decreased muscle mass, serum creatinine overestimates kidney function in elderly persons, especially women. Young persons, men, and black persons often have higher muscle mass and higher serum creatinine concentration at a given GFR compared with older persons. Patients with advanced liver disease produce lower amounts of creatine (the precursor of creatinine) and have muscle wasting, resulting in a correspondingly lower serum creatinine at a given GFR. Certain medications (such as cimetidine and trimethoprim) inhibit organic cation transporters and block tubular secretion

of creatinine, resulting in a higher serum creatinine without a change in GFR. Conversely, in patients who have chronic kidney disease (CKD) with intact tubular function, creatinine secretion increases, thus leading to a progressive overestimation of GFR. Creatinine clearance is a measure of the volume of plasma that is cleared of creatinine by the kidney per unit of time and can be directly measured from a 24-hour urine collection to approximate the GFR (Table 1). The “adequacy” or “completeness” of the collection is estimated by the total excreted creatinine per 24 hours. For a 20- to 50-year-old man, creatinine excretion should be 18.5-25.0 mg/kg body weight and 16.522.4 mg/kg body weight for a woman of the same age. Because of the secretion of creatinine in the proximal tubule, the direct measurement of creatinine clearance tends to overestimate GFR. Nonetheless, the 24-hour urine collection with an adequate collection judged by the creatinine excreted is used to estimate GFR as well as excretion of other electrolytes and metabolic products such as calcium, phosphate, and urate. Blood urea nitrogen (BUN) is derived from the metabolism of proteins. BUN concentration is a poor marker of kidney function because it is not produced at a constant rate and is reabsorbed along the tubules; furthermore, alterations in renal blood flow markedly influence tubular reabsorption and excretion. Urea clearances significantly underestimate GFR but may be useful in estimating GFR <15 mL/min/1.73 m2.

F i g u r e 1 . The relationship between serum creatinine and glomerular filtration rate (GFR). Example A illustrates that a small increase in the serum creatinine level in the reference range (in this case, 0.8 to 1.2 mg/dL [70.7-106 µmol/L]) reflects a relatively large change in GFR (120 to 78 mL/min/1.73 m2). Example B illustrates that a relatively greater increase in the serum creatinine level (in the high range of 3.0 to 4.5 mg/dL [265-398 µmol/L]) reflects a proportionately smaller change in GFR (35 to 22 mL/min/1.73 m2).

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Clinical Evaluation of Kidney Function

Table 1. Methods for Estimating Kidney Function Method

Considerations

Application

Overestimates GFR 10%-20%

Useful in pregnancy, extremes of age and weight, amputees, and patients with cirrhosis

Creatinine Clearance UCr (mg/dL) × 24-hour urine volume (mL/24 h)/SCr (mg/dL) × 1440 (min/24 h)

Incomplete or excessive 24-hour urine collections limit accuracy Serum Cystatin C Levels are affected by thyroid status, diabetic status, inflammation, and glucocorticoid use

More accurate in elderly population and patients with cirrhosis

Most accurate when eGFR is 15-60 mL/min/1.73 m2

Chronic kidney disease when eGFR is 15-60 mL/ min/1.73 m2

Modification of Diet in Renal Disease (MDRD) Study Equationa GFR = 175 × (SCr)-1.154 × (age)-0.203 × 0.742 (if female) or × 1.212 (if black)

Underestimates GFR when GFR >60 mL/min/1.73 m2 Less accurate in populations with normal or near normal eGFR, extremes of age and weight, amputees, in pregnancy, and in patients with cirrhosis Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration Equationa GFR = 141 × min(SCr/κ,1)α × max(SCr/κ,1)-1.209 × 0.993age × 1.018 (if female) × 1.159 (if black)b

Superior to CGE and MDRD equations in patients with eGFR >60 mL/min/1.73 m2

More accurate than MDRD equation in elderly population

Most accurate when eGFR is 15-60 mL/min/1.73 m2

Improved accuracy when age is <65 years

Cockcroft-Gault Equation (CGE) CrCl =

(140 − age) × (weight in kg) × ( 0.85 if female) (72 × SCr)

Underestimates GFR in obesity Overestimates GFR when BMI <25 Takes into account lean body weight, age, and gender Radionuclide Kidney Clearance Scanning Iothalamate GFR scan Diethylenetriamine pentaacetic acid (DTPA) GFR scan

Most precise method; expensive

Kidney donor evaluation if eGFR is borderline for donation; research; prediction of eGFR following nephrectomy

CrCl = creatinine clearance; eGFR = estimated glomerular filtration rate; GFR = glomerular filtration rate; SCr = serum creatinine (mg/dL); UCr = urine creatinine (mg/dL). aMathematical bκ

equations recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative for estimation of GFR.

is 0.7 for women and 0.9 for men; α is -0.329 for women and -0.411 for men; min = the minimum of SCr/κ or 1; max = the maximum of SCr/κ or 1.

Serum cystatin C is an alternative marker of GFR less influenced than serum creatinine by age, gender, muscle mass, and body weight. Cystatin C is produced by all nucleated cells, completely filtered by glomeruli, and then metabolized by

renal tubules; serum levels thus provide an index of GFR, without the need to measure urine excretion. Serum cystatin C is more sensitive in identifying milder decrements in kidney function than serum creatinine.

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Clinical Evaluation of Kidney Function

Estimation of Glomerular Filtration Rate Isotopic markers that are filtered and not secreted (for example, iothalamate) provide very accurate estimates of GFR but are expensive and not available in routine clinical practice. However, the correlation of these forms of measurement with serum creatinine, age, race, and gender has led to the development of equations that provide a more accurate estimation of GFR than creatinine clearance (see Table 1). Three estimation equations are commonly used: the Cockcroft-Gault equation (CGE), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation. Each equation was developed in different study populations and uses different variables to provide an estimation of the GFR. Because of this, these equations tend to be more accurate when used in specific clinical circumstances. For example, the MDRD study equation has been validated in multiple populations with CKD but frequently underestimates GFR when it is >60 mL/min/ 1.73 m2. The CKD-EPI equation performs better at higher (normal) values of GFR. Despite its long history and widespread use, the CGE equation is slightly less accurate than these newer equations for estimating GFR. Accurate estimation of GFR is important for appropriate adjustment of drug dosing in the elderly population and in patients with kidney disease. Historically, drug-dosing guidelines have been developed based on the estimated creatinine clearance derived from the CGE equation. For the purposes of drug dosing, the CGE equation correlates adequately with GFR as estimated by the MDRD study equation. Most clinical laboratories employ the MDRD study equation to estimate GFR, with higher levels of GFR reported as “>60 mL/ min/1.73 m2.” Physicians may therefore ignore other signs or symptoms of CKD (such as proteinuria) after erroneously assuming that a level reported as normal means an absence of structural kidney disease. Conversely, the appropriateness of labeling a patient who has a stable GFR around 55 mL/min/1.73 m2 (apart from guiding appropriate drug dosing) as having stage 3 CKD, with no other signs of kidney disease, remains unclear. Key Point

• The Modification of Diet in Renal Disease study equation has been validated in multiple populations with chronic kidney disease but frequently underestimates the glomerular filtration rate (GFR) when it is >60 mL/min/1.73 m2, whereas the Chronic Kidney Disease Epidemiology Collaboration equation performs better at higher (normal) values of GFR; the Cockcroft-Gault equation is slightly less accurate than these newer equations for estimating GFR but is the basis for drug dosing guidelines.

catch” midstream collection or a bladder catheterization, and should be examined within 1 hour to minimize the breakdown of formed elements.

Urine Dipstick or Automated Urinalysis Specific Gravity Specific gravity is the ratio of the weight of urine to an equal quantity of the weight of water. Normal specific gravity of urine is approximately 1.010, and the typical range of 1.005 to 1.030 varies depending on hydration status and the capacity of the kidneys to maximally dilute and concentrate the urine. Specific gravity is used to estimate the urine osmolality, with a specific gravity of 1.010 approximating a urine osmolality of 300 mOsm/ kg H2O, indicating isosmolar urine; higher or lower values reflect concentrated and dilute urine, respectively.

pH A typical high-protein American diet results in the need to excrete a high acid load, primarily via the kidneys. The urine in this case is relatively more acidic, ranging from 5.0 to 6.0. An alkaline pH of ≥7.0 can occur in strict vegetarians, postprandially, in type 1 (distal) renal tubular acidosis, or with infections caused by urease-splitting organisms such as Proteus and Pseudomonas species.

Albumin Albumin is the predominant protein detected on urine dipstick, which detects albumin excretion graded as trace (5-30 mg/dL), 1+ (30 mg/dL), 2+ (100 mg/dL), 3+ (300 mg/dL), and 4+ (>1000 mg/dL). Highly alkaline urine specimens can produce false-positive results on dipstick testing for protein. The sulfosalicylic acid (SSA) test can be used to detect the presence of not only albumin but also other proteins that are not detected with the urine dipstick, such as urine light chains or immunoglobulins. The possibility of cast nephropathy should be raised in patients with acute kidney injury (AKI) when the urine dipstick reads negative or trace for protein, but the urine shows increased positivity for protein by the SSA test. This should be confirmed by immunoelectrophoresis, which can detect urine light chains or Bence-Jones proteins.

Glucose Glycosuria typically occurs when the plasma glucose concentration is >180 to 200 mg/dL (10.0-11.1 mmol/L). Generalized proximal tubular dysfunction (termed Fanconi syndrome) may result in glycosuria in the absence of hyperglycemia or in pregnancy with a change in threshold for glucose.

Ketones

Interpretation of the Urinalysis Dipstick analysis and microscopic examination of the urine are indicated in the clinical evaluation of kidney function for both acute and chronic kidney disease (Table 2). The sample is best collected without contamination, which requires a “clean

Ketones in the urine are associated with diabetic ketoacidosis, salicylate toxicity, isopropyl alcohol poisoning, and states of starvation such as alcoholic ketoacidosis. Because the urine dipstick detects acetoacetate but not β-hydroxybutyrate, patients who are ketotic with β-hydroxybutyrate as the only ketone body do not display a positive urine dipstick for 3

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Each of the numbered items is followed by lettered answers. Select the ONE lettered answer that is BEST in each case.

Item 1 A 43-year-old man is evaluated during a routine physical examination. He has no current symptoms and no prior medical history. Family history is notable for diabetes mellitus and hypertension in two first-degree relatives. He takes no medications. On physical examination, initial blood pressure measurement is 144/86 mm Hg; repeat measurement after 5 minutes of rest are 136/86 mm Hg and 134/88 mm Hg. BMI is 32. The remainder of the examination is normal. Laboratory studies show normal serum creatinine and plasma glucose levels. In addition to lifestyle modifications, which of the following is the most appropriate next step in the management of this patient’s blood pressure? (A) (B) (C) (D)

Initiate a low-dose ACE inhibitor Initiate low-dose chlorthalidone Order ambulatory blood pressure monitoring Recheck blood pressure in 1 year

Item 2 A 74-year-old woman is evaluated for a 1-week history of intermittent painless gross hematuria. She has a 3-year history of stage G4/A3 chronic kidney disease due to diabetic nephropathy, a 12-year history of type 2 diabetes mellitus, diabetic retinopathy, and hypertension. Medications are lisinopril, furosemide, insulin glargine, and insulin lispro. On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 128/85 mm Hg, pulse rate is 76/min, and respiration rate is 15/min. BMI is 28. The lungs are clear. There are no abdominal masses or costovertebral angle tenderness. There is no edema. Laboratory studies: Creatinine Estimated glomerular filtration rate Urinalysis

2.6 mg/dL (230 µmol/L) 23 mL/min/1.73 m2 2+ protein; 25-50 erythrocytes/hpf; 0 leukocytes/hpf; no erythrocyte casts

Which of the following is the most appropriate diagnostic test to perform in this patient? (A) (B) (C) (D)

Contrast-enhanced CT of the abdomen and pelvis Gadolinium-enhanced MRI of the abdomen and pelvis Radiography of the abdomen and pelvis Ultrasonography of the abdomen and pelvis

Item 3 A 45-year-old man is evaluated during a new patient visit. He immigrated to the United States from Serbia 4 years ago and was diagnosed with Balkan endemic nephropathy at that time. His kidney function has remained stable, and his

only symptoms are mild nocturia and urinary frequency. Medical history is otherwise unremarkable. He takes no medications. On physical examination, temperature is 37.1 °C (98.7 °F), blood pressure is 138/82 mm Hg, pulse rate is 76/min, and respiration rate is 12/min. BMI is 26. The remainder of the examination is normal. Laboratory studies: Hemoglobin Electrolytes Creatinine Glucose Estimated glomerular filtration rate Urinalysis

Self-Assessment Test

Directions

9.6 g/dL (96 g/L) Normal 1.7 mg/dL (150.1 µmol/L) Normal 35 mL/min/1.73 m2 Specific gravity 1.005; 2+ glucose; 10-20 erythrocytes/hpf

An increased risk of which of the following is most likely in this patient? (A) (B) (C) (D)

Diabetes mellitus Intracranial cerebral aneurysm Renal cell carcinoma Transitional cell carcinoma

Item 4 A 64-year-old man is evaluated for a 6-week history of intermittent red-colored urine. He notes fatigue but otherwise feels well. Medical history includes hypertension, mechanical mitral valve replacement due to myxomatous degeneration, and calcium oxalate nephrolithiasis. He is a current smoker with a 60-pack-year history. Medications are amlodipine, warfarin, and aspirin. On physical examination, temperature is 37.6 °C (99.7 °F), blood pressure is 112/72 mm Hg, and pulse rate is 98/min. BMI is 30. Examination of the heart reveals a metallic click with a grade 2/6 cardiac systolic murmur that radiates to the axilla. The lungs are clear. There is no costovertebral angle tenderness. The remainder of the examination is unremarkable. Urinalysis is dipstick positive for 3+ blood, 1+ protein, and no leukocyte esterase or nitrites; on microscopic examination, there are no cells or casts, although calcium oxalate crystals are seen. Which of the following is the most likely cause of this patient’s clinical findings? (A) Bladder cancer (B) Glomerulonephritis (C) Hemoglobinuria (D) Nephrolithiasis

Item 5 A 62-year-old man is evaluated during a follow-up visit for hypertension. His clinic blood pressure readings during the 91

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Answers and Critiques Answer:

Educational Objective: Manage prehypertension. In addition to lifestyle modifications, rechecking blood pressure in 1 year is appropriate for this patient with prehypertension. Although the eighth report of the Joint National Committee (JNC) did not address prehypertension, JNC 7 defined prehypertension as a systolic blood pressure of 120139 mm Hg or a diastolic blood pressure of 80-89 mm Hg in the absence of preexisting end-organ disease (for example, diabetes mellitus, chronic kidney disease, or cardiovascular disease). Lifestyle modifications, including a low salt diet and exercise regimen, can be used to effectively reduce blood pressure in patients with prehypertension. Patients with prehypertension may also adopt the DASH (Dietary Approaches to Stop Hypertension) diet, which emphasizes vegetables, fruits, whole grains, legumes, and low-fat dairy products and limits sweets, red meat, and saturated/total fat, along with dedicated weight loss planning. Appropriate follow-up for those with prehypertension occurs at annual visits. The mean blood pressure in this patient (even accounting for the potential of inaccurate technique upon initial check-in) falls within the prehypertensive range, making lifestyle modifications and follow-up in 1 year the appropriate management. If blood pressures measuring 140/90 mm Hg or greater were documented, this would require repeat measurements for at least three visits over the period of at least 1 week of more to establish a diagnosis of hypertension. Although there is an increased risk of stroke and cardiovascular disease for every level of blood pressure above 115/75 mm Hg and an increased risk of the development of hypertension, treatment of prehypertension using pharmacologic therapy (such as an ACE inhibitor or diuretic) has not yet been demonstrated to reduce this risk. Ambulatory blood pressure monitoring records blood pressures periodically during normal activities. It is indicated primarily for diagnosis of suspected white coat hypertension (persistently elevated blood pressure readings in the office without evidence of end-organ damage) or to confirm a poor response to antihypertensive medication. It may also be useful in assessing for masked hypertension (evidence of end-organ damage without apparent elevated blood pressures) or for evaluating episodic or resistant hypertension. It is not indicated for this patient with evidence of prehypertension. Key Point

â&#x20AC;˘ Prehypertension is managed with lifestyle modifications and annual follow-up visits to monitor blood pressure.

Bibliography McInnes G. Pre-hypertension: how low to go and do drugs have a role? Br J Clin Pharmacol. 2012 Feb;73(2):187-93. [PMID: 21883385]

Item 2

Answer:

Educational Objective: Select the most appropriate imaging modality for a patient with chronic kidney disease. Ultrasonography of the abdomen and pelvis is appropriate for this patient with chronic kidney disease (CKD). She requires imaging studies to evaluate her kidneys and genitourinary tract in order to rule out a structural lesion or tumor as the source of gross hematuria. Ultrasonography is an appropriate initial screening test because it can provide necessary information without exposure to the risks associated with the administration of contrast agents in patients with severe CKD who are at increased risk of contrast-induced nephropathy (CIN) and gadolinium-induced nephrogenic systemic fibrosis (NSF). This patient has risk factors for CIN (older age, elevated serum creatinine, diabetes mellitus); therefore, a contrast-enhanced CT to evaluate for lesions of the kidneys and genitourinary tract as a cause of her hematuria should be performed only if similar information cannot be obtained from tests that entail less risk to the patient. The use of gadolinium in MRI studies is relatively contraindicated in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 due to the increased risk of NSF. Although most NSF cases have occurred in patients with end-stage kidney disease, there have been isolated case reports occurring in patients with stage G4 CKD. Gadolinium-enhanced MRI is therefore contraindicated in these patients unless there is a compelling clinical indication and the patient is fully informed of the risk of NSF. Radiography of the abdomen and pelvis may be a reasonable test to rule out nephrolithiasis. However, the patient does not have symptoms suggestive of nephrolithiasis, and a plain radiograph would not provide information to determine whether there are structural lesions in the kidneys or genitourinary tract.

Answers and Critiques

Item 1

Key Point

â&#x20AC;˘ Ultrasonography is an appropriate imaging modality for patients with chronic kidney disease to avoid adverse events such as contrast-induced nephropathy or nephrogenic systemic fibrosis.

Bibliography Manjunath V, Perazella MA. Imaging patients with kidney disease in the era of NSF: can it be done safely? Clin Nephrol. 2011 Apr;75(4):279-85. [PMID: 21426881]

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