Glomerulonephritis — What It Is, Why Kidney Biopsy Is Essential, and How It Is Treated
Glomerulonephritis is not a single disease it is a family of conditions characterised by immune-mediated inflammation of the glomeruli, the kidney's microscopic filtering units. Different types of glomerulonephritis are caused by different immune mechanisms, affect different parts of the glomerulus, produce different patterns of injury on kidney biopsy, and require completely different treatments. A patient with nephrotic syndrome from minimal change disease needs steroids. A patient with an identical clinical presentation from FSGS may be steroid-resistant and require calcineurin inhibitors or rituximab. A patient with RPGN from ANCA vasculitis needs cyclophosphamide and plasma exchange started within hours or days. Treating without knowing which condition is present using empirical therapy without biopsy means giving the wrong treatment to many patients, with all the side effects of immunosuppression and none of the benefit.
This is the fundamental reason kidney biopsy is essential in glomerulonephritis. It is not a precautionary or academic investigation it is the diagnostic procedure that determines which disease is present and therefore which treatment will work. At KIMS Secunderabad, kidney biopsies are performed under real-time ultrasound guidance by the nephrology team, and processed in the NABL-accredited laboratory using all three components required for complete glomerular disease diagnosis: light microscopy, immunofluorescence, and electron microscopy. The biopsy result is reviewed and interpreted by Dr. Aswini Dutt T the KIMS nephrologist with specific subspecialty expertise in glomerular disease in the context of the patient's full clinical picture before the treatment decision is made.
The glomerulus — what gets inflamed and why it matters
Each kidney contains approximately one million glomeruli tiny tufts of capillaries enclosed in Bowman's capsule, responsible for filtering blood at high pressure. The glomerulus has several distinct structures, each vulnerable to different types of immune attack:
Glomerular basement membrane (GBM)
The filtration barrier. Immune complexes depositing along the GBM characterise membranous nephropathy; antibodies against the GBM itself cause anti-GBM disease (Goodpasture's syndrome).
Mesangium
The matrix supporting the glomerular capillaries. IgA nephropathy is defined by IgA deposition in the mesangium; mesangial proliferative lupus nephritis (Class II) shows mesangial immune deposits.
Endothelium
The inner lining of glomerular capillaries. ANCA vasculitis attacks the endothelium, causing necrotising lesions and crescent formation.
Podocytes
The specialised cells covering the outer surface of glomerular capillaries. Podocyte injury disrupts the filtration barrier, causing massive proteinuria. Minimal change disease, FSGS, and membranous nephropathy all primarily injure podocytes.
The pattern of injury on kidney biopsy which structures are affected, what immunoglobulins are deposited, what the ultrastructural appearance looks like on electron microscopy defines the specific diagnosis and determines the treatment.
The most common types of glomerulonephritis — and what makes each distinct
Effective treatment of glomerular disease requires precise diagnosis. At KIMS, we combine clinical expertise with advanced biopsy techniques to distinguish between these complex conditions:
IgA Nephropathy — Most Common Primary GN in India
IgA nephropathy (Berger's disease) is characterised by IgA1 immune complexes depositing in the mesangium — particularly prevalent in India. It typically presents in young adults with haematuria (often triggered by an upper respiratory infection — 'synpharyngitic haematuria') and variable proteinuria. The diagnosis is made on kidney biopsy using the Oxford MEST-C score to grade histological severity. Treatment at KIMS: Low-risk patients are managed conservatively with ACE inhibitors or ARBs. Moderate to high-risk patients are considered for targeted-release budesonide (Nefecon), the first FDA-approved drug for IgA nephropathy, or systemic steroids. Rapidly progressive cases may require cyclophosphamide-based immunosuppression.
Membranous Nephropathy — Nephrotic Syndrome in Adults Over 40
Characterised by subepithelial immune complex deposition along the glomerular basement membrane, producing the 'spike and dome' appearance. It is the leading cause of nephrotic syndrome in adults over 40. Identification of the PLA2R antigen now allows for non-invasive diagnosis in many cases and precise monitoring of treatment response. Treatment at KIMS: Primary membranous nephropathy with significant proteinuria is treated with rituximab (the preferred first-line agent) or the Ponticelli regimen (cyclophosphamide plus steroids). Secondary cases are managed by treating the underlying cause (malignancy, infection, or drugs).
FSGS (Focal Segmental Glomerulosclerosis)
FSGS describes a pattern of scarring that can be primary (immune podocyte injury), secondary (obesity, reflux, or reduced nephron mass), or genetic. Distinguishing between these is critical: • Primary FSGS: May respond to steroids, tacrolimus, or rituximab. • Secondary FSGS: Requires treating the underlying cause (e.g., weight loss) and is generally non-responsive to immunosuppression. • Genetic FSGS: Requires specialized management rather than traditional immunosuppression.
Rapidly Progressive Glomerulonephritis (RPGN) — The Emergency
RPGN is a nephrological emergency characterized by rapidly deteriorating kidney function and "crescents" on biopsy. Causes include: • ANCA-associated vasculitis: Treated with high-dose steroids and rituximab or cyclophosphamide. • Anti-GBM disease (Goodpasture's): Requires emergency plasma exchange to remove antibodies. • Immune complex RPGN: Including severe Lupus Nephritis or IgA nephropathy. At KIMS, emergency biopsies for suspected RPGN are arranged within 24 hours because every day without treatment costs irreversible kidney function.
Lupus Nephritis — The Most Complex Glomerular Disease
Lupus Nephritis (LN) affects 50–60% of SLE patients. Classification into 6 classes via biopsy is mandatory for treatment: • Class I & II: Usually require no specific kidney therapy. • Class III & IV: Require aggressive induction with mycophenolate mofetil and steroids, often adding voclosporin (approved via the AURORA trial). • Class V: Treated as membranous LN. Without a biopsy, the distinction between simple observation and aggressive immunosuppression cannot be made safely.
Why the complete biopsy workup matters — LM, IF, and EM
A kidney biopsy is only as useful as the pathological analysis of the tissue obtained. The complete renal biopsy workup requires three techniques:
Light microscopy (LM)
Identifies glomerular architecture changes hypercellularity, crescent formation, sclerosis, GBM thickening and assesses tubular, interstitial, and vascular changes. The foundation of all biopsy reports.
Immunofluorescence (IF)
Identifies the pattern and location of immunoglobulin and complement deposition essential for classifying immune complex glomerulonephritis. IgA mesangial staining = IgA nephropathy. Granular subepithelial IgG = membranous nephropathy. 'Full house' (IgG + IgA + IgM + C3 + C1q) = lupus nephritis. Linear GBM IgG = anti-GBM disease. Without IF, immune complex GN subtypes cannot be reliably classified.
Electron microscopy (EM)
Allows nanometre-resolution visualisation of the GBM and deposit locations essential for thin basement membrane disease (GBM thinning invisible on LM and IF), Alport syndrome (GBM lamellation), membranous nephropathy subtype classification (deposit location relative to GBM), and identification of organised deposits (fibrillary deposits in fibrillary GN, microtubules in immunotactoid GN) that are invisible on LM.
Many hospitals and diagnostic centres in Hyderabad perform kidney biopsy but only conduct light microscopy outsourcing immunofluorescence and electron microscopy with turnaround times of 2 to 4 weeks. At KIMS, all three components are performed in-house in the NABL-accredited laboratory, with the complete report available within 5 to 7 working days. A biopsy without EM cannot diagnose Alport syndrome, thin basement membrane disease, or accurately subtype membranous nephropathy conditions where the treatment decision depends on what EM shows. A cheaper biopsy that misses the diagnosis is not cheaper when the cost of misdiagnosis is measured.
Frequently Asked Questions — Glomerulonephritis
The earliest and most common signs of glomerulonephritis are abnormalities detected on urine testing not symptoms felt by the patient. Blood in the urine (haematuria — visible as pink or tea-coloured urine, or detected only on microscopy as red blood cells and red cell casts) and protein in the urine (foamy or frothy urine, or detected on urine dipstick as protein) are the cardinal findings. These may appear months or years before kidney function (eGFR) begins to decline. Swelling of the legs and face from fluid retention (oedema) indicates nephrotic syndrome heavy proteinuria causing hypoalbuminaemia and fluid accumulation. Rapidly worsening kidney function over days to weeks, combined with haematuria and red cell casts, indicates RPGN — a nephrological emergency requiring immediate evaluation.
In adults with proteinuria, haematuria, or unexplained CKD where the diagnosis is not clear from clinical assessment and serology alone, kidney biopsy is almost always required for definitive diagnosis. The few situations where treatment may be started without biopsy include: IgA nephropathy with low-risk features in a young adult where the clinical picture is highly characteristic (synpharyngitic haematuria, mesangial IgA on IF if ever biopsied), or minimal change disease presenting as classic nephrotic syndrome in a child under 8 (where empirical steroid therapy is the standard approach). In adults, the clinical presentation of different glomerulonephritis subtypes is too similar to treat safely without biopsy. At KIMS, the decision to biopsy is made by Dr. Aswini Dutt T at the consultation based on the clinical picture, laboratory findings, and the likely impact the biopsy result will have on treatment decisions.
IgA nephropathy (Berger's disease) is the most common primary glomerulonephritis in India characterised by mesangial IgA deposition on kidney biopsy. It typically presents in young adults with haematuria (often triggered by throat infection) and variable proteinuria. Low-risk IgA nephropathy (proteinuria below 1g/day, stable eGFR) is managed with ACE inhibitor or ARB and lifestyle measures. Moderate-to-high-risk disease (proteinuria above 1g/day, declining eGFR, or aggressive Oxford MEST-C histological score) is treated with targeted-release budesonide (Nefecon — FDA approved 2021 specifically for IgA nephropathy), or systemic immunosuppression in selected cases. The treatment plan is based on the biopsy Oxford score and proteinuria response to initial conservative management.
The kidney biopsy procedure at KIMS takes 15 to 20 minutes from local anaesthetic injection to completion. Real-time ultrasound guidance ensures the needle is correctly positioned in the lower pole kidney cortex throughout. The patient is observed for 6 hours post-procedure with blood pressure and pulse monitoring and urine haematuria checks before discharge home the same day. The most common post-biopsy finding is mild blood in the urine for 24 hours — expected and not a complication. Significant bleeding requiring intervention occurs in less than 0.5% of biopsies at experienced centres. The kidney biopsy procedure at KIMS is safe, well-tolerated, and performed routinely including as an emergency in RPGN cases.
Rapidly Progressive Glomerulonephritis (RPGN) is a clinical syndrome of acute kidney injury developing over days to weeks, with active urinary sediment (blood and red cell casts in the urine), caused by necrotising glomerulonephritis with crescent formation on kidney biopsy. It is a nephrological emergency because, without immediate treatment, RPGN can cause irreversible kidney failure within weeks. The three main causes — ANCA vasculitis, anti-GBM disease, and immune complex nephritis each require different emergency treatment. Emergency kidney biopsy at KIMS is arranged within 24 hours of clinical suspicion of RPGN — the biopsy directs immediate treatment: plasma exchange for anti-GBM disease and severe ANCA vasculitis, cyclophosphamide and steroids for ANCA. Hours matter in RPGN.
No — glomerulonephritis and kidney infection (pyelonephritis) are entirely different conditions. Pyelonephritis is a bacterial infection of the kidney caused by bacteria ascending from the bladder, presenting with fever, chills, loin pain, and bacteria in the urine, treated with antibiotics. Glomerulonephritis is immune-mediated inflammation of the kidney's filtering units — typically not infectious in cause (though some types are triggered by or associated with infections), presenting with blood and protein in the urine and progressive kidney function decline, treated with immunosuppressive medications. Some infections particularly Streptococcal throat or skin infections can trigger a form of glomerulonephritis (post-infectious or post-streptococcal GN) but this is an immune response to the infection, not the infection itself attacking the kidney.
KIMS Secunderabad — Dr. Aswini Dutt T with specific subspecialty expertise in glomerular disease (IgA nephropathy, membranous nephropathy, FSGS, lupus nephritis, ANCA vasculitis), NABL-accredited pathology laboratory performing complete renal biopsy workup (light microscopy + immunofluorescence + electron microscopy) in-house, emergency kidney biopsy for RPGN within 24 hours, real-time ultrasound-guided biopsy technique, results consultation with the nephrologist who requested the biopsy. NABH and NABL accredited.