Glomerulonephritis (GN) in children represents a complex diagnostic entity that encompasses a spectrum of kidney disorders characterized by inflammation of the glomeruli.

While some forms may resolve with minimal intervention, others progress to chronic kidney disease (CKD) or end-stage renal failure if not promptly and accurately identified.

According to a 2023 review in Pediatric Nephrology, the incidence of biopsy-proven GN in children varies globally, with post-infectious and IgA nephropathy being the most prevalent.

Clinical Presentation: Beyond the Classical Triad

Classic textbook signs such as hematuria, edema, and hypertension do not always present simultaneously in pediatric patients. A study by Dr. Franz Schaefer, Chair of the European Society for Paediatric Nephrology (ESPN), emphasizes that microscopic hematuria is often the sole clue, especially in early or atypical cases. Parents may notice puffiness around the eyes, often misattributed to allergies or fatigue. Additionally, systemic features such as fever, joint pain, or rash may hint at systemic vasculitic or autoimmune etiologies (e.g., lupus nephritis), necessitating a broader diagnostic workup beyond renal parameters.

Initial Workup: The Role of Laboratory Screening

A comprehensive urinalysis remains the cornerstone of initial assessment. The presence of red blood cell casts strongly suggests glomerular origin.

Blood tests should include:

- Serum creatinine and eGFR to evaluate baseline renal function

- Complement levels (C3 and C4), as low C3 may indicate post-infectious GN, membranoproliferative GN, or lupus nephritis

- Anti-streptolysin O (ASO) titer in suspected post-streptococcal cases

- ANA, dsDNA, and ANCA panels for autoimmune and vasculitic causes

Imaging and Renal Ultrasound: Non-invasive But Limited

While renal ultrasound is not diagnostic, it assists in ruling out structural anomalies and assessing kidney size and echogenicity. Hyperechogenicity may correlate with chronicity, while is more typical of acute processes. Nevertheless, imaging must be integrated with biochemical and histological findings to reach a definitive diagnosis.

Indications for Renal Biopsy: Precision Requires Tissue

Renal biopsy remains the gold standard for definitive diagnosis. The 2022 KDIGO guidelines underscore that biopsy should be performed when nephrotic-range proteinuria coexists with hematuria or when renal function deteriorates without clear etiology. Biopsy helps to differentiate minimal change disease from focal segmental glomerulosclerosis or detect immune-complex mediated conditions such as membranous nephropathy.

Histopathological evaluation combined with immunofluorescence and electron microscopy can uncover immune deposits, segmental sclerosis, or crescent formation—each guiding therapy decisions.

Advances in Non-invasive Biomarkers: Future of Diagnosis?

Emerging research into urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) shows promise in distinguishing inflammatory from non-inflammatory nephropathies. A 2024 multi-center trial led by Dr. Anisa Cherif at the University of Geneva demonstrated that elevated NGAL levels predicted biopsy-proven proliferative GN with 87% sensitivity.

Genetic testing is also becoming relevant, particularly in familial or syndromic presentations, where mutations in COL4A3/A4/A5 genes may indicate Alport syndrome.

Multidisciplinary Approach: Pediatric Nephrology is a Team Effort

Given the potential for systemic involvement, diagnosis often requires collaboration between pediatricians, nephrologists, rheumatologists, and infectious disease specialists. Prompt referral to pediatric nephrology is essential when red flags such as rising creatinine, nephrotic syndrome features, or persistent hypertension are identified.

Diagnosing glomerulonephritis in children demands clinical vigilance, strategic use of laboratory and imaging tools, and judicious application of biopsy. Early and accurate identification not only guides targeted therapy but also preserves long-term renal function and quality of life. As diagnostic techniques evolve, incorporating molecular and urinary biomarkers alongside traditional methods will refine pediatric GN diagnosis in years to come.