What are the indications for a renal biopsy in patients with suspected kidney disease or impaired renal function?

Indications for Renal Biopsy

Perform a renal biopsy when the diagnosis cannot be established by non-invasive means and the histologic findings will directly change management or provide critical prognostic information. 1

Primary Clinical Indications

Proteinuria-Based Indications

• Significant proteinuria >1 g/day, especially with glomerular hematuria and/or cellular casts, mandates biopsy to identify the underlying glomerular disease and guide immunosuppressive therapy. 1
• Nephrotic syndrome (>3.5 g/day proteinuria with hypoalbuminemia and edema) is the most common indication for biopsy in adults, representing approximately 45% of all biopsies performed. 2
• Rapidly increasing proteinuria or sudden onset of nephrotic syndrome requires urgent biopsy, as this pattern suggests aggressive glomerular disease requiring immediate treatment. 3

Acute Kidney Injury

• AKI stage 3 (≥3-fold increase in creatinine or creatinine ≥4.0 mg/dL) warrants biopsy when pre-renal and obstructive causes are excluded. 4
• AKI stages 1-2 should be considered for biopsy if the etiology remains unclear after initial evaluation. 4
• In rapidly progressive glomerulonephritis (RPGN) with positive MPO- or PR3-ANCA serology and compatible clinical presentation, start immunosuppressive therapy immediately without waiting for biopsy results, though biopsy should still be performed for confirmation and prognostic assessment. 4

Chronic Kidney Disease

• Unexplained decline in eGFR, particularly >2 mL/min/1.73m² per year when eGFR <60 mL/min/1.73m², requires biopsy to identify potentially treatable causes. 4, 1
• Persistent isolated glomerular hematuria with dysmorphic red blood cells or red cell casts, after excluding urologic causes, indicates glomerulonephritis requiring biopsy. 1
• Combined proteinuria and hematuria strongly suggests glomerular disease and is a clear indication for biopsy. 5

Systemic Disease with Renal Involvement

Lupus Nephritis

• Biopsy is indicated when reproducible proteinuria ≥0.5 g/24h is present, especially with glomerular hematuria and/or cellular casts, as the histologic class determines treatment intensity. 1

Monoclonal Gammopathy of Renal Significance (MGRS)

• Any patient with unexplained kidney disease and a detectable monoclonal protein requires biopsy to diagnose MGRS-associated lesions including light chain deposition disease, amyloidosis, or immunotactoid glomerulonephritis. 4, 1
• The biopsy must include Congo red staining to exclude amyloidosis and IgG subclass staining when heavy chain deposits are present. 4
• Older age (≥70 years) should not discourage biopsy, as most MGRS-related diseases occur after age 50. 1

ANCA-Associated Vasculitis

• Biopsy provides critical prognostic information through assessment of glomerular sclerosis, crescents, and tubulointerstitial damage, with diagnostic yield as high as 91.5% in GPA. 4
• However, in patients with pulmonary-renal syndrome and positive MPO- or PR3-ANCA, initiate treatment immediately without delaying for biopsy. 4

Special Populations

Diabetic Patients

Biopsy diabetic patients when atypical features suggest non-diabetic kidney disease, as approximately 40% of diabetic patients with kidney injury have non-diabetic renal disease (NDRD). 3

Atypical features requiring biopsy include:

• Rapidly declining GFR (>5 mL/min/1.73m² per year) 3
• Rapidly increasing or nephrotic-range proteinuria 3
• Active urinary sediment with hematuria, dysmorphic RBCs, or cellular casts 3
• Absence of diabetic retinopathy despite long-standing diabetes 3
• Short diabetes duration (<5 years) before onset of kidney disease 3
• Evidence of systemic disease suggesting alternative diagnosis 3

Do not biopsy diabetic patients with typical diabetic kidney disease: long-standing diabetes, diabetic retinopathy present, gradual GFR decline with progressive albuminuria, and bland urinary sediment. 3

Cancer Patients

• New-onset significant proteinuria (>1 g/day) in cancer patients requires biopsy to distinguish paraneoplastic glomerulopathy from treatment-related toxicity. 1
• Worsening kidney function when diagnosis cannot be established by clinical means warrants biopsy. 1

Technical Requirements for Adequate Biopsy

Tissue Adequacy

• At least 8-10 glomeruli are required to diagnose or exclude specific histopathologic patterns with reasonable confidence. 1
• For transplant biopsies evaluating rejection, at least 25 glomeruli improve statistical prediction of outcomes based on glomerulosclerosis. 4
• Minimum of two biopsy cores for transplant dysfunction increases sensitivity from 91% (single core) to 99%. 4

Processing Requirements

All biopsies must include three modalities: 4, 1

• Light microscopy with special stains (H&E, PAS, trichrome, Jones methenamine silver, Congo red)
• Immunofluorescence or immunohistochemistry (IgG, IgM, IgA, C3, C1q, kappa and lambda light chains)
• Electron microscopy for ultrastructural examination

For MGRS evaluation, add IgG subclass staining when IgG deposits are present, and consider liquid chromatography-mass spectrometry when immunofluorescence is inconclusive. 4

Situations Where Biopsy May Be Deferred

Three specific scenarios allow treatment without biopsy:

• PLA2R antibody-positive membranous nephropathy with nephrotic syndrome and normal eGFR 1
• MPO+ or PR3+ ANCA vasculitis with compatible clinical presentation and rapid deterioration 4, 1
• Anti-GBM disease with positive anti-GBM antibodies and pulmonary-renal syndrome requiring urgent plasma exchange 4, 1

In these cases, initiate treatment immediately but still perform biopsy for confirmation and prognostic assessment once the patient is stabilized. 4

Safety Considerations and Contraindications

Bleeding Risk

• Major complications requiring intervention occur in approximately 4% of biopsies, with life-threatening complications in <0.1%. 1, 6, 7
• Risk factors for bleeding include female gender, advanced renal insufficiency, and prolonged baseline PTT. 7
• Limit needle passes to ≤4 to reduce bleeding risk. 1
• Observe patients for 12-24 hours post-biopsy, as >90% of major complications manifest within 24 hours. 7

Alternative Approaches

• Transjugular kidney biopsy is the preferred alternative in patients with coagulopathy, severe obesity, or single functioning kidney. 1, 6
• Laparoscopic biopsy may be considered in select cases where percutaneous approach is unsafe. 6

Kidney Size Considerations

• Normal kidney size (≥9 cm) with preserved echogenicity indicates suitable tissue for biopsy. 1
• Markedly shrunken kidneys (<8 cm) with increased echogenicity suggest advanced irreversible disease where biopsy yield is low and risk may outweigh benefit. 1

Common Pitfalls to Avoid

• Do not assume all proteinuria in diabetic patients is diabetic nephropathy—atypical features mandate biopsy to avoid missing treatable alternative diagnoses. 3
• Do not delay biopsy in younger patients with monoclonal gammopathy, as MGUS is uncommon in this age group and suggests more aggressive disease. 3
• Do not avoid biopsy based solely on advanced age, as many glomerular diseases and MGRS occur predominantly in patients >50 years. 1
• Do not rely on bleeding time as a screening test—it has substantial limitations; PFA-100 is more valuable for identifying patients with impaired hemostasis. 7
• Do not delay immunosuppression in ANCA vasculitis waiting for biopsy when clinical presentation and serology are diagnostic. 4