What are the indications for performing a kidney biopsy in children?

Indications for Kidney Biopsy in Pediatric Patients

Kidney biopsy in children should be performed when the diagnosis cannot be established by non-invasive means and the histopathological findings will directly alter treatment decisions or provide essential prognostic information. 1

Primary Indications for Kidney Biopsy in Children

Steroid-Resistant Nephrotic Syndrome (SRNS)

• Perform kidney biopsy after a minimum of 8 weeks of corticosteroid therapy (60 mg/m²/day for 4 weeks, then 40 mg/m² on alternate days for 4 weeks) when complete or partial remission is not achieved. 1
• The biopsy is essential because SRNS encompasses multiple histologic entities—focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN)—each requiring different therapeutic approaches and carrying distinct prognoses. 1, 2, 3
• In children with SRNS, FSGS accounts for 15-43% of cases, MCD for 10-34%, and MPGN for 16% in various series, making histologic diagnosis critical for management. 2, 3, 4

Nephrotic Syndrome with Atypical Features at Presentation

• Biopsy is indicated when nephrotic syndrome presents with any of the following features:

  • Age <1 year or >12 years at onset 1, 5
  • Persistent gross hematuria 1, 6
  • Hypertension at presentation 6, 4
  • Renal insufficiency (elevated serum creatinine or reduced eGFR) 1, 2, 6
  • Low complement C3 levels 2
  • Nephritis (defined as the combination of reduced eGFR, hematuria, and hypertension) 6

• The combination of steroid resistance after 6 weeks AND/OR nephritis at presentation yields optimal sensitivity (0.80) and specificity (0.75) for predicting FSGS, making these the most evidence-based triggers for biopsy. 6

Steroid-Dependent or Frequently Relapsing Nephrotic Syndrome

• Consider kidney biopsy in children with steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS) before initiating calcineurin inhibitor therapy or other second-line immunosuppression. 1
• While not universally required, biopsy may reveal FSGS or other lesions that predict poor response to therapy and worse long-term outcomes, potentially altering the treatment approach. 5, 6

Persistent Glomerular Hematuria

• Biopsy is indicated for persistent isolated glomerular hematuria (dysmorphic RBCs >80% or red cell casts) when other causes have been excluded. 1, 7
• In children with recurrent episodes of gross hematuria, IgA nephropathy accounts for 84.5% of cases on biopsy, making histologic diagnosis valuable for prognosis and family counseling. 3

Acute Kidney Injury of Unclear Etiology

• Perform kidney biopsy in children with AKI stage 3 (≥3-fold increase in creatinine or creatinine ≥4.0 mg/dL) when prerenal and obstructive causes are excluded. 7
• Consider biopsy in AKI stages 1-2 if the etiology remains unclear after initial evaluation, particularly when rapidly progressive glomerulonephritis (RPGN) is suspected. 7

Systemic Disease with Suspected Renal Involvement

• Biopsy is indicated for suspected lupus nephritis when reproducible proteinuria ≥0.5 g/24h is present, especially with glomerular hematuria and/or cellular casts. 1, 7
• Among children with lupus nephritis, biopsy reveals class IV+V in 43%, class IIIA in 43%, and class IIB in 14%, with treatment varying substantially by histologic class. 3
• Biopsy should be performed in Henoch-Schönlein purpura nephritis when there is persistent proteinuria, declining renal function, or nephrotic-range proteinuria to guide immunosuppressive therapy. 3, 4

Situations Where Biopsy May Be Deferred

Typical Steroid-Sensitive Nephrotic Syndrome

• Do NOT perform routine kidney biopsy in children aged 1-12 years presenting with typical nephrotic syndrome (edema, proteinuria >40 mg/m²/h, hypoalbuminemia <2.5 g/dL) who achieve complete remission within 4 weeks of daily prednisone therapy. 1
• In this population, minimal change disease accounts for 80-90% of cases, making empiric steroid therapy without biopsy the standard approach. 1, 2

Congenital Nephrotic Syndrome (Age <1 Year)

• Genetic testing should be performed FIRST in infants presenting with nephrotic syndrome before age 1 year, as genetic screening identifies the underlying abnormality in >85% of cases. 1
• Kidney biopsy in congenital nephrotic syndrome should be reserved for cases where genetic diagnosis cannot be established OR when eGFR declines to <30 ml/min/1.73 m² and the biopsy would inform rare diagnoses (e.g., congenital membranous nephropathy due to anti-NEP antibodies). 1

Serologically Confirmed ANCA Vasculitis

• In children with rapidly progressive glomerulonephritis and positive MPO or PR3 ANCA serology with compatible clinical presentation, immunosuppressive therapy should be initiated immediately without waiting for biopsy results, though biopsy should still be performed for confirmation and prognostic assessment. 7

Technical Requirements for Adequate Biopsy

• At least 8-10 glomeruli are required to diagnose or exclude specific histopathologic patterns with reasonable confidence. 1, 7
• All biopsies must include three modalities: light microscopy with special stains (PAS, H&E, trichrome, Jones' silver), immunofluorescence or immunohistochemistry (IgG, IgA, IgM, C3, C4, C1q, fibrin, κ and λ light chains), and electron microscopy for ultrastructural examination. 1, 7
• Percutaneous ultrasound-guided renal biopsy achieves adequate tissue samples in 97.7% of cases in children, with major complications (subcapsular hematoma) occurring in approximately 11% but rarely requiring transfusion. 3

Critical Pitfalls to Avoid

• Do NOT assume all proteinuria in children with systemic disease (e.g., diabetes, obesity) is secondary to that condition without considering primary glomerular disease—biopsy when clinical features are atypical. 7
• Do NOT delay biopsy in steroid-resistant nephrotic syndrome beyond 8 weeks of adequate corticosteroid therapy, as early histologic diagnosis allows timely initiation of appropriate second-line therapy. 1
• Do NOT perform kidney biopsy in children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs, as they are unlikely to have clinically significant renal disease requiring intervention. 8
• In resource-limited settings where genetic testing or histopathology is unavailable, immediate immunosuppressive treatment with calcineurin inhibitors may be started empirically in SRNS, but biopsy should be pursued when feasible. 1

Age-Specific Considerations

• The threshold age of >12 years as an automatic indication for biopsy at nephrotic syndrome presentation is debatable and should not be applied rigidly. 5
• Instead, focus on clinical and biochemical parameters: children with two or more atypical features (hematuria, hypertension, renal insufficiency, low C3) should undergo biopsy regardless of age. 2
• The decision to perform biopsy in adolescents (>12 years) should weigh the increased incidence of non-MCD lesions against the uniform initial steroid therapy recommended by guidelines—consider biopsy BEFORE steroids if atypical features are present. 5