Evaluation of the Patient with Renal Disease

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Diagnosis

Clinical Presentation

  • Renal disease often is asymptomatic or presents with nonspecific complaints. Its presence is frequently first noted on abnormal routine laboratory data, generally as an elevated serum creatinine (Cr) level. An abnormal urinalysis or sediment, with proteinuria, hematuria, or pyuria, may also indicate renal disease.
  • When the decline in renal function is acute or severe, a variety of nonspecific symptoms may be present. Generalized malaise, worsening hypertension, dependent or generalized edema, or decreasing urine output may accompany more advanced chronic renal insufficiency, whereas hyperkalemia and metabolic acidosis are more prominent in acute disease.

Diagnostic Testing

The focus of the initial evaluation of the patient with renal disease is to determine the need for emergent dialysis. Then, investigations to identify the etiology are undertaken, while differentiating components of acute and chronic disease.

  • 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), which can be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using the age, gender, race (African American or non-African American), and serum creatinine of the patient. The Modification of Diet in Renal Disease (MDRD) formula is similar to the CKD-EPI formula, but tends to overdiagnose CKD.
    • With both equations, CKD is not considered present when the eGFR is >60 mL/min/1.73 m unless other evidence of renal damage (e.g., proteinuria) is present for at least 3 months.
    • Use of cystatin C to estimate the GFR may be better able to accurately classify patients in the 45–60 mL/min/1.73 m range, although this has not been shown to improve outcomes or to provide better predictions of risk.1
    • Unlike the complex formulae 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 females.
  • 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 (for 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 can be estimated from a spot urine protein-to-creatinine ratio in patients whose serum creatinine level is in the steady state. A normal ratio is <250 mg of protein per gram of Cr. A 24-hour urine collection for protein can be obtained when the serum Cr is not at a stable baseline and is a more precise assessment of proteinuria.
      • Hematuria (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) suggest a glomerular source of bleeding and can 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 a urinary tract infection (UTI), parenchymal infections such as pyelonephritis or abscess, or acute interstitial nephritis (AIN). WBC casts are consistent with 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 document the presence of two kidneys, assess size, and identify hydronephrosis or renal cysts. Small kidneys (<9 cm) generally reflect chronic disease, although kidneys may be large (generally >13 cm) in diabetes, HIV, deposition disorders, and polycystic kidney disease. 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. The presence of hydronephrosis suggests obstructive nephropathy. Retroperitoneal fibrosis can encase the ureters and prevent dilation despite the presence of an obstruction.
    • CT has less utility in the evaluation of kidney disease because the iodinated contrast dye can be nephrotoxic and may cause worsening renal function. 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 renal failure or dialysis dependence.2 Guidelines that limit the use of gadolinium in at-risk patients have decreased the incidence of NSF. The available contrast agents should be used with caution when necessary.
    • 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 can determine diagnosis, classify disease, guide therapy, and provide prognostic information in many settings, particularly in the evaluation of glomerular or deposition diseases. Biopsy of a native kidney may be indicated in adults with unexplained proteinuria, hematuria, or renal dysfunction. Biopsy of a renal transplant allograft may be necessary to distinguish acute rejection from medication toxicity and other causes of renal dysfunction. Shrunken fibrotic kidneys are unlikely to yield useful diagnostic information; they also have an increased risk of postprocedural bleeding, and biopsy should generally be avoided in these cases.
    • Preparative measures for native kidney biopsy include avoiding aspirin and antiplatelet agents for 5–7 days and reversing anticoagulation before procedure, ultrasonography (to document the presence of two kidneys and assess size and location), urinalysis or urine culture to exclude infection, and blood pressure control. If uremic platelet dysfunction is suspected by an elevated bleeding time (>10 minutes) or 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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Diagnosis

Clinical Presentation

  • Renal disease often is asymptomatic or presents with nonspecific complaints. Its presence is frequently first noted on abnormal routine laboratory data, generally as an elevated serum creatinine (Cr) level. An abnormal urinalysis or sediment, with proteinuria, hematuria, or pyuria, may also indicate renal disease.
  • When the decline in renal function is acute or severe, a variety of nonspecific symptoms may be present. Generalized malaise, worsening hypertension, dependent or generalized edema, or decreasing urine output may accompany more advanced chronic renal insufficiency, whereas hyperkalemia and metabolic acidosis are more prominent in acute disease.

Diagnostic Testing

The focus of the initial evaluation of the patient with renal disease is to determine the need for emergent dialysis. Then, investigations to identify the etiology are undertaken, while differentiating components of acute and chronic disease.

  • 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), which can be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using the age, gender, race (African American or non-African American), and serum creatinine of the patient. The Modification of Diet in Renal Disease (MDRD) formula is similar to the CKD-EPI formula, but tends to overdiagnose CKD.
    • With both equations, CKD is not considered present when the eGFR is >60 mL/min/1.73 m unless other evidence of renal damage (e.g., proteinuria) is present for at least 3 months.
    • Use of cystatin C to estimate the GFR may be better able to accurately classify patients in the 45–60 mL/min/1.73 m range, although this has not been shown to improve outcomes or to provide better predictions of risk.1
    • Unlike the complex formulae 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 females.
  • 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 (for 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 can be estimated from a spot urine protein-to-creatinine ratio in patients whose serum creatinine level is in the steady state. A normal ratio is <250 mg of protein per gram of Cr. A 24-hour urine collection for protein can be obtained when the serum Cr is not at a stable baseline and is a more precise assessment of proteinuria.
      • Hematuria (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) suggest a glomerular source of bleeding and can 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 a urinary tract infection (UTI), parenchymal infections such as pyelonephritis or abscess, or acute interstitial nephritis (AIN). WBC casts are consistent with 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 document the presence of two kidneys, assess size, and identify hydronephrosis or renal cysts. Small kidneys (<9 cm) generally reflect chronic disease, although kidneys may be large (generally >13 cm) in diabetes, HIV, deposition disorders, and polycystic kidney disease. 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. The presence of hydronephrosis suggests obstructive nephropathy. Retroperitoneal fibrosis can encase the ureters and prevent dilation despite the presence of an obstruction.
    • CT has less utility in the evaluation of kidney disease because the iodinated contrast dye can be nephrotoxic and may cause worsening renal function. 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 renal failure or dialysis dependence.2 Guidelines that limit the use of gadolinium in at-risk patients have decreased the incidence of NSF. The available contrast agents should be used with caution when necessary.
    • 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 can determine diagnosis, classify disease, guide therapy, and provide prognostic information in many settings, particularly in the evaluation of glomerular or deposition diseases. Biopsy of a native kidney may be indicated in adults with unexplained proteinuria, hematuria, or renal dysfunction. Biopsy of a renal transplant allograft may be necessary to distinguish acute rejection from medication toxicity and other causes of renal dysfunction. Shrunken fibrotic kidneys are unlikely to yield useful diagnostic information; they also have an increased risk of postprocedural bleeding, and biopsy should generally be avoided in these cases.
    • Preparative measures for native kidney biopsy include avoiding aspirin and antiplatelet agents for 5–7 days and reversing anticoagulation before procedure, ultrasonography (to document the presence of two kidneys and assess size and location), urinalysis or urine culture to exclude infection, and blood pressure control. If uremic platelet dysfunction is suspected by an elevated bleeding time (>10 minutes) or 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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