Evaluation of the Patient With Renal Disease

Diagnosis

Clinical Presentation

  • Most patients with renal disease are asymptomatic. Renal disease is often initially discovered because of abnormal routine laboratory data, specifically an elevated serum creatinine (Cr) level. An abnormal urinalysis or sediment, with proteinuria, hematuria, or pyuria, may also indicate renal disease, requiring further evaluation.
  • The presentation of acute kidney injury (AKI) can be quite variable, ranging from constitutional symptoms of generalized malaise to more concerning symptoms such as worsening hypertension, dependent or generalized edema, decreasing urine output, foamy urine, weight changes, or poor appetite. With advanced chronic kidney disease (CKD), patients may start to experience nausea, vomiting, a metallic taste in the mouth, and lethargy. A wide range of electrolyte abnormalities including hyperkalemia, hypocalcemia, hyperphosphatemia, and metabolic acidosis may also develop.

Diagnostic Testing

During the initial evaluation of a patient with renal disease, it is important to determine if there is a need for emergent dialysis by obtaining pertinent laboratory and imaging studies. Additional testing is then performed to identify the underlying etiology.

Basic diagnostic testing

  • A basic evaluation includes electrolytes (with calcium and phosphorus), Cr, blood urea nitrogen (BUN), and albumin. When Cr is stable over days to weeks, it can be used to calculate an estimated glomerular filtration rate (eGFR). eGFR can be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the Modification of Diet in Renal Disease (MDRD) formula. Historically, these equations have incorporated a modifier for race. However, with the growing acknowledgment that race is a social construct, and not a biologic one, the American Society of Nephrology and the National Kidney Foundation have advocated for removing this variable.
  • With both equations, CKD is not diagnosed when the eGFR is >60 mL/min/1.73 m2 unless other evidence of renal damage (e.g., proteinuria) is present for at least 3 months.
  • Use of cystatin C to estimate the GFR can more accurately classify patients in the eGFR range of 45–60 mL/min/1.73 m2, although this has not been shown to improve outcomes or to provide better predictions of risk.1
  • Unlike the complex formulae described above, the Cockcroft–Gault equation can be calculated manually, and yields an estimated creatinine clearance, which is equal to ([140 − age]/[serum creatinine in mg/dL]) × (weight in kg/72). The equation should be multiplied by 0.85 for women.
  • These equations are not helpful in estimating renal function when the creatinine is not in steady state.

Urine studies

  • Routine urine studies include a urine dipstick (for protein, blood, glucose, leukocyte esterase, nitrites, pH, and specific gravity) as well as a freshly voided specimen for microscopic examination of urine sediment (cells, casts, and crystals). The urine sample is centrifuged at 2100 rpm for 5 minutes, and then most of the supernatant is poured off. The pellet is resuspended by gently tapping the side of the tube.
  • Proteinuria and albuminuria can be estimated from a spot urine protein-to-creatinine ratio or albumin-to-creatinine ratio in patients whose serum creatinine level is in the steady state. The ratio is expressed in milligrams of protein or albumin per gram of creatinine. The 2012 KDIGO guidelines have revised the definition for albuminuria based on the urinary albumin-to-creatinine ratio as being normal to mildly increased (A1, <30 mg/g), moderately increased (A2, 30–300 mg/g), and severely increased (A3, >300 mg/g).2 These values can serve as a useful prognostic tool for adverse events. The term microalbuminuria is no longer used. A normal ratio for proteinuria is <250 mg/g. A 24-hour urine collection for protein can be obtained when the serum Cr is not at a stable baseline.
  • Hematuria, which is defined as more than three red blood cells (RBCs) per high-power field on an unspun specimen, can represent an infectious, inflammatory, or malignant process anywhere along the urinary tract. Dysmorphic RBCs (with rounded protuberances) are suggestive of a glomerular source of injury. These may be accompanied by RBC casts formed within the tubules. The absence of RBCs in a patient with a positive dipstick for blood suggests hemolysis or rhabdomyolysis, forms of pigment nephropathy.
  • White blood cells (WBCs) in the urine represent an infectious or inflammatory process. This may be seen with urinary tract infection (UTI), kidney parenchymal infections such as pyelonephritis or abscess, or acute interstitial nephritis (AIN). WBC casts can accompany WBCs in the urine and are suggestive of AIN and pyelonephritis but can also be seen as part of an active sediment in inflammatory glomerular diseases.
  • Additional biochemistry tests can be ordered to evaluate for specific etiologies and will be discussed in the individual sections below.

Imaging

  • Renal ultrasonography can be helpful in acute and chronic kidney diseases. It can document the presence of two kidneys, assess organ size and distribution of renal cysts, and identify hydronephrosis in the setting of obstruction. Small kidneys (<9 cm) generally reflect chronic disease. Diseases including diabetes, HIV, deposition disorders, and polycystic kidney disease are associated with large kidneys (generally >13 cm). A discrepancy in kidney size of >2 cm suggests chronic disease in a unilateral kidney, such as that seen in renal artery stenosis with atrophy of the affected kidney. Retroperitoneal fibrosis can encase the ureters and prevent dilation despite the presence of an obstruction.
  • CT with contrast has less utility in the evaluation of kidney disease because the iodinated contrast dye can be nephrotoxic. However, noncontrast helical CT scanning has become the test of choice in evaluating nephrolithiasis.
  • MRI and magnetic resonance angiography (MRA) can be helpful in evaluating renal masses, detecting renal artery stenosis, and diagnosing renal vein thrombosis. Unlike standard arteriography, MRA does not require the administration of nephrotoxic contrast agents but does employ gadolinium-based contrast agents, which are associated with the development of nephrogenic systemic fibrosis (NSF) in patients with advanced kidney disease or dialysis dependence.3 Guidelines that limit the use of gadolinium in at-risk patients have decreased the incidence of NSF.
  • Radionuclide scanning uses technetium isotopes to assess the contribution of each kidney to the overall renal function, providing important information if unilateral nephrectomy is being considered for malignancy or for living donation. Renal scanning is also useful in transplantation, where renal uptake and excretion of the tracer can be followed.

Diagnostic procedures

  • Kidney biopsy should be considered in adults with unexplained proteinuria, hematuria, or renal dysfunction. It can determine diagnosis, classify disease, guide therapy, and provide prognostic relevance in many settings, particularly in the evaluation of glomerular or deposition diseases. Biopsy of a renal transplant allograft may be necessary to distinguish allograft rejection from medication toxicity and other causes of renal dysfunction. Biopsy is unlikely to provide useful diagnostic information when the kidneys are very small, suggestive of advanced chronicity and fibrotic kidneys. This scenario also carries an increased risk of postprocedural bleeding, and biopsy should generally be avoided in these cases.
  • Preparative measures for native kidney biopsy include avoiding aspirin, NSAIDs, and antiplatelet agents for 5–7 days. Blood pressure must be controlled, and anticoagulation must be reversed before the procedure. Ultrasonography (to document the presence of two kidneys and assess size and location) and urinalysis or urine culture to exclude infection should also be performed prior to the procedure. If uremic platelet dysfunction is suspected by abnormal platelet function assays, IV desmopressin acetate (DDAVP at 0.3 μg/kg) can be infused 30 minutes before biopsy. Patients on dialysis should not receive heparin immediately after the biopsy. If body habitus precludes a percutaneous approach, a transjugular renal biopsy can be performed.
  • A hemoglobin drop of approximately 10% is common after the procedure. Difficulty voiding after the procedure may represent urethral clot obstructing the flow of urine.

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