What laboratory values are typically elevated in end‑stage renal disease?

Laboratory Values Elevated in End-Stage Renal Disease

In end-stage renal disease (ESRD, defined as GFR <15 mL/min/1.73 m² or requiring dialysis), serum creatinine and blood urea nitrogen (BUN) are the primary elevated laboratory markers, with creatinine typically exceeding 4.0 mg/dL and BUN often markedly elevated, though the degree varies based on protein intake and catabolic state. 1

Primary Markers of Kidney Function

Serum Creatinine

• Creatinine rises progressively as GFR declines, with ESRD (stage G5) defined by GFR <15 mL/min/1.73 m² 1
• In acute-on-chronic presentations, creatinine may increase to ≥4.0 mg/dL, which defines stage 3 acute kidney injury when accompanied by acute rise 1
• Creatinine is less influenced by extrarenal factors than BUN, making it the more accurate marker of renal function 2, 3

Blood Urea Nitrogen (BUN)

• BUN elevation is independently associated with progression to ESRD and is a useful marker for predicting kidney disease progression beyond what GFR alone provides 4
• BUN levels are typically disproportionately elevated relative to creatinine in ESRD patients, though the BUN:creatinine ratio can vary significantly 2, 5
• Normal BUN:creatinine ratio is 10-15:1, but in ESRD this ratio often exceeds 20:1 due to increased protein catabolism, decreased renal perfusion, or high protein intake 5, 6

Additional Laboratory Abnormalities

Proteinuria/Albuminuria

• Severely increased albuminuria (ACR >300 mg/g or >30 mg/mmol) or nephrotic-range proteinuria (PCR >3500 mg/d or >350 mg/mmol) commonly accompanies ESRD, though non-albuminuric CKD phenotypes exist 1, 7
• Albuminuria should be assessed alongside GFR for complete CKD staging, as the combination predicts mortality and progression risk 1

Calculated Serum Osmolality

• While calculated serum osmolality (cSosm) rises concomitantly with BUN in advanced CKD stages, BUN itself is the more clinically relevant marker for predicting renal outcomes rather than cSosm 4

Critical Diagnostic Considerations

Distinguishing Acute from Chronic

• ESRD represents chronic kidney disease requiring ≥3 months of documented dysfunction (GFR <15 mL/min/1.73 m²), not acute kidney injury 1, 8
• Evidence of chronicity includes: prior documentation of reduced eGFR for >3 months, persistent albuminuria on multiple occasions, or imaging showing reduced kidney size 8
• Acute rises in creatinine (≥0.3 mg/dL within 48 hours or ≥1.5 times baseline within 7 days) superimposed on ESRD indicate acute kidney injury requiring urgent evaluation 9, 8

Interpretation Pitfalls

• Never interpret BUN or creatinine in isolation—both absolute values and their ratio provide diagnostic information 2, 3
• Factitious elevations must be excluded before attributing values to renal disease 3
• A BUN:creatinine ratio ≥20:1 may indicate prerenal azotemia, increased protein catabolism, GI bleeding, or steroid use rather than intrinsic ESRD progression 5, 6
• Patients with high BUN:creatinine ratios show greater disagreement between measured creatinine clearance and estimated GFR, requiring cautious interpretation 6

Monitoring Requirements

• Quarterly monitoring of creatinine and eGFR is recommended for stages 4-5 CKD approaching ESRD 8
• Both eGFR and albuminuria must be quantified together, as eGFR alone is insufficient for staging and prognosis 1