What is the appropriate workup for a patient with impaired renal function, as indicated by elevated creatinine (kidney function test), Blood Urea Nitrogen (BUN), and low estimated Glomerular Filtration Rate (eGFR)?

Workup for Elevated Creatinine, BUN, and Low eGFR

Begin by repeating serum creatinine and obtaining a urinalysis with microscopy within days to weeks to distinguish acute kidney injury from chronic kidney disease, while simultaneously measuring urine albumin-to-creatinine ratio (UACR) on a spot urine sample. 1, 2

Immediate Laboratory Assessment

Core Initial Tests

• Repeat serum creatinine within days to weeks—do not assume chronicity based on a single abnormal value, as this could represent acute kidney injury (AKI) or acute kidney disease (AKD) rather than chronic kidney disease (CKD) 1
• Obtain UACR on spot urine sample to quantify albuminuria (normal <30 mg/g; microalbuminuria 30-300 mg/g; macroalbuminuria >300 mg/g) 1, 3, 2
• Urinalysis with microscopy to identify red blood cell casts, dysmorphic RBCs, white blood cells, or other sediment abnormalities that indicate specific pathologies 2
• Measure cystatin C and calculate eGFRcr-cys if eGFRcr is expected to be inaccurate due to extremes of muscle mass, dietary factors (high-protein, vegetarian, ketogenic diets), malnutrition, chronic illness (cancer, heart failure, cirrhosis), or medications affecting creatinine secretion 1

Additional Laboratory Studies

• Complete blood count with differential 2
• Serum electrolytes, particularly potassium 3, 2
• Blood glucose and HbA1c 2
• Lipid panel 2
• Hepatic function panel 2

Critical interpretation point: BUN and creatinine are best interpreted together—an extrarenal problem produces a BUN:creatinine ratio >25:1, while intrinsic renal failure produces a ratio of approximately 10:1 4. However, both conditions can coexist 4.

Establishing Chronicity (3-Month Rule)

CKD requires proof that abnormalities have persisted for at least 3 months. 1, 5 Establish chronicity through:

• Review of past eGFR measurements from medical records 1
• Review of past UACR or proteinuria measurements and prior urine microscopy 1
• Renal imaging (ultrasound or CT) showing reduced kidney size (<9 cm longitudinal length) or cortical thinning 1, 2
• Medical history of conditions known to cause CKD (diabetes, hypertension, glomerulonephritis) 1
• Repeat measurements at the 3-month point and beyond 1, 2

Do not wait 3 months to initiate treatment if CKD is deemed likely based on clinical indicators—begin kidney-protective interventions at first presentation if imaging shows structural damage or history strongly suggests chronicity 1.

Determining the Underlying Cause

Systematic Etiologic Evaluation

Establish the cause using a structured approach 1:

• Clinical context and history: Duration of symptoms, medication exposures (NSAIDs, aminoglycosides, contrast agents), recent illnesses 1, 2
• Family history: Polycystic kidney disease, hereditary nephritis, genetic conditions 1
• Social and environmental factors: Occupational exposures, herbal supplements, heavy metals 1
• Physical examination: Blood pressure measurement, volume status assessment, signs of systemic disease 1
• Targeted laboratory testing based on clinical suspicion 1
• Renal imaging: Ultrasound as first-line to assess kidney size, echogenicity, and rule out obstruction 1
• Kidney biopsy: Consider when diagnosis remains uncertain and results would change management, particularly for suspected glomerulonephritis, vasculitis, or rapidly progressive disease 1

Common Pitfalls to Avoid

• Creatine supplementation can transiently elevate serum creatinine without true kidney damage—ask specifically about supplement use 6
• High-protein diets increase BUN disproportionately to creatinine, mimicking prerenal azotemia 1
• Medications affecting tubular secretion (trimethoprim, cimetidine, cobicistat) falsely elevate creatinine without changing true GFR 1
• Extreme muscle mass (bodybuilders or severe sarcopenia) makes eGFRcr unreliable—use eGFRcr-cys instead 1

When to Obtain More Accurate GFR Measurement

Measure GFR directly using plasma or urinary clearance of an exogenous filtration marker (iothalamate, iohexol, or inulin) when 1:

• eGFRcr-cys is expected to be inaccurate (extreme obesity class III, advanced cirrhosis, high catabolic states, exogenous steroid use)
• Precise GFR is needed for critical decisions (kidney-cleared chemotherapy dosing, living kidney donation evaluation)
• Clinical evidence of uremia exists despite relatively preserved serum creatinine 7

Urgent Nephrology Referral Criteria

Refer immediately to nephrology if any of the following are present 2:

• Rapidly increasing albuminuria or nephrotic-range proteinuria (UACR >2200 mg/g)
• Rapidly declining eGFR (>5 mL/min/1.73 m²/year)
• eGFR <30 mL/min/1.73 m² (Stage 4-5 CKD)
• Uncertainty about etiology despite initial workup
• Active urinary sediment with RBC casts or dysmorphic RBCs suggesting glomerulonephritis

Initial Management Pending Complete Workup

Blood Pressure Control

• Target BP <130/80 mmHg if CKD is confirmed 3, 2
• Initiate ACE inhibitor or ARB if hypertension is present with UACR ≥30 mg/g 3, 2
• Monitor serum creatinine and potassium within 1-2 weeks after starting renin-angiotensin system inhibitors 2

Nephrotoxin Avoidance

• Avoid aminoglycosides, tetracyclines, and other nephrotoxic antibiotics when alternatives exist 3
• Review and discontinue NSAIDs if possible 3
• Ensure adequate hydration before any contrast-enhanced imaging 1

Ongoing Monitoring Strategy

• Reassess eGFR and UACR every 6-12 months for Stage 2 CKD, more frequently for Stage 3 or higher 3
• Monitor electrolytes (particularly potassium) every 6-12 months, or more frequently if on ACE inhibitor/ARB or mineralocorticoid receptor antagonist 3
• Assess volume status at each visit, as fluid retention can worsen kidney function 2