What are the causes and management of impaired renal function indicated by elevated BUN (Blood Urea Nitrogen), creatinine, and decreased eGFR (estimated Glomerular Filtration Rate)?

Causes of Abnormal Renal Laboratory Values (BUN, Creatinine, eGFR)

Elevated BUN, creatinine, and decreased eGFR are primarily caused by impaired kidney function, with pre-renal, intrinsic renal, and post-renal causes requiring specific management approaches based on the underlying etiology. 1

Pre-Renal Causes

Volume Depletion/Dehydration

• Decreased renal perfusion due to hypovolemia 2
• Causes include:
  • Excessive diuresis
  • Gastrointestinal losses (vomiting, diarrhea)
  • Hemorrhage
  • Poor oral intake
  • Excessive sweating
  • Burns

Decreased Cardiac Output

• Heart failure with reduced ejection fraction
• Cardiogenic shock
• Severe valvular disease

Vascular Issues

• Renal artery stenosis 1
• Systemic vasodilation (sepsis, anaphylaxis)
• Hepatorenal syndrome

Medications

• ACE inhibitors/ARBs (can cause functional decline in GFR) 3
• NSAIDs (affect renal autoregulation) 1
• Diuretics (especially with volume depletion) 1

Intrinsic Renal Causes

Acute Tubular Necrosis

• Ischemic (prolonged pre-renal state)
• Nephrotoxic (medications, contrast agents, pigments) 4

Glomerular Diseases

• Diabetic kidney disease (leading cause of end-stage renal disease) 2
• Glomerulonephritis (various immune-mediated causes) 1
• Hypertensive nephrosclerosis 1

Tubulointerstitial Diseases

• Interstitial nephritis (often medication-induced) 1
• Pyelonephritis
• Crystal nephropathy (uric acid, oxalate)

Vascular Diseases

• Vasculitis
• Thrombotic microangiopathy
• Malignant hypertension

Post-Renal Causes

Urinary Tract Obstruction

• Nephrolithiasis
• Prostatic hypertrophy
• Tumors (bladder, prostate, retroperitoneal)
• Urethral strictures
• Neurogenic bladder 1

Special Considerations

BUN/Creatinine Ratio

• Elevated BUN/Creatinine ratio (>20:1) suggests:
  • Pre-renal azotemia 2
  • Gastrointestinal bleeding
  • Catabolic states
  • High protein diet
  • Corticosteroid use
• BUN/Creatinine ratio is independently associated with worse outcomes in heart failure 5

Discordant BUN and Creatinine

• High BUN with relatively normal creatinine may indicate:
  • Volume depletion 6
  • Heart failure 5
  • Increased protein catabolism
• Low creatinine despite significant kidney dysfunction may occur with:
  • Severe muscle wasting
  • Liver disease
  • Excessive creatinine secretion 7

Dilutional Effects

• Fluid overload can cause dilutional reduction in serum proteins and may affect hemoglobin levels 8

Diagnostic Approach

1. Assess chronicity:

   • Review previous laboratory values (abnormalities present for ≥3 months suggest CKD) 1
   • Check kidney size on imaging (small kidneys suggest chronicity)

2. Evaluate volume status:

   • Physical examination (edema, jugular venous distension)
   • Weight changes
   • Vital signs (orthostatic changes)

3. Urinalysis:

   • Proteinuria suggests glomerular disease
   • Hematuria with casts suggests glomerulonephritis
   • Pyuria/bacteria suggest infection
   • Eosinophiluria suggests interstitial nephritis

4. Quantify proteinuria:

   • Urine albumin-to-creatinine ratio (UACR) 2
   • 24-hour urine protein

5. Imaging:

   • Renal ultrasound to assess kidney size and rule out obstruction

Management Principles

1. Treat underlying cause:

   • Correct volume depletion if pre-renal
   • Relieve obstruction if post-renal
   • Treat specific kidney diseases

2. Medication management:

   • Avoid nephrotoxic medications
   • Adjust medication doses based on eGFR
   • Monitor potassium levels with ACE inhibitors/ARBs 3
   • Do not discontinue ACE inhibitors/ARBs for minor increases in serum creatinine (<30%) in the absence of volume depletion 2

3. Blood pressure control:

   • Target <130/80 mmHg if albuminuria is present 1
   • Use ACE inhibitors or ARBs for those with elevated UACR (30–299 mg/g creatinine) 2

4. Diabetes management:

   • Consider SGLT2 inhibitors for patients with type 2 diabetes and CKD 2
   • Consider GLP-1 receptor agonists for cardiovascular risk reduction 2

5. Dietary considerations:

   • Protein intake should be approximately 0.8 g/kg body weight per day for non-dialysis CKD 2
   • Higher protein intake (1.0–1.2 g/kg/day) for patients on dialysis 2

Referral to Nephrology

Refer patients to a nephrologist when:

• eGFR <30 mL/min/1.73m² 2, 1
• Rapid decline in kidney function (>5 mL/min/1.73m² per year) 1
• Persistent significant albuminuria (UACR ≥300 mg/g) 2, 1
• Difficult-to-manage hypertension
• Uncertainty about the etiology of kidney disease 2, 1

Common Pitfalls to Avoid

• Misinterpreting transient changes in kidney function as CKD
• Overlooking non-renal causes of elevated creatinine (e.g., creatine supplements)
• Inappropriate discontinuation of ACE inhibitors/ARBs
• Missing pre-renal causes such as volume depletion
• Failing to adjust medication doses based on eGFR
• Ignoring albuminuria as a marker of kidney damage
• Overlooking heart failure as a cause of kidney dysfunction