Understanding the 5 Main Histopathological Subtypes of Chronic Glomerulonephritis

Chronic glomerulonephritis (CGN) is a progressive kidney disorder characterized by persistent inflammation and damage to the glomeruli—the tiny filtering units of the kidneys. While patients often present with overlapping clinical symptoms—including hematuria, proteinuria, edema, hypertension, and gradual decline in kidney function—accurate diagnosis and personalized treatment depend far more on histopathological evaluation than on symptoms alone. In fact, distinguishing between subtypes based solely on clinical features is notoriously difficult. That's why kidney biopsy remains the gold standard: it reveals the precise structural changes occurring at the microscopic level, guiding prognosis and therapeutic decisions.

Why Histology Matters More Than Symptoms

Unlike many other chronic diseases, CGN doesn't follow a "one-size-fits-all" pattern. Two patients with identical blood pressure readings, urine protein levels, and serum creatinine values may have entirely different underlying pathologies—and therefore require vastly different management strategies. For example, one may respond dramatically to corticosteroids, while another might need immunosuppressants or even targeted biologics. This underscores the critical importance of renal biopsy and expert pathological interpretation in modern nephrology practice.

The Five Core Histopathological Subtypes

1. Minimal Change Disease (MCD) — Deceptively Benign Under the Microscope

Despite its name, Minimal Change Disease is not "minimal" in impact—it's actually the most common cause of nephrotic syndrome in children and a significant contributor in adults. Under light microscopy, kidney tissue appears nearly normal; no obvious structural abnormalities are visible. However, electron microscopy reveals the telltale loss of podocyte foot processes—a key clue that explains the massive protein leakage. MCD typically responds rapidly to corticosteroid therapy, making early recognition vital for preserving long-term kidney health.

2. Mesangial Proliferative Glomerulonephritis — IgA Dominance in Asia, Broader Spectrum Globally

This subtype is defined by increased cellularity in the mesangial area—the central supporting region of the glomerulus. It's further classified based on immune deposits: IgA-dominant (IgA nephropathy) and non-IgA variants (e.g., IgM or C3-dominant). Notably, IgA nephropathy is the most prevalent primary glomerular disease worldwide—and especially common across East Asia, where it accounts for roughly 30–40% of all native kidney biopsies. Its hallmark is recurrent macroscopic or microscopic hematuria, often triggered by mucosal infections. Emerging therapies like targeted complement inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors are now reshaping its long-term outlook.

3. Membranous Nephropathy — A Thickened Filter With Autoimmune Roots

In membranous nephropathy, the glomerular basement membrane becomes diffusely thickened due to immune complex deposits along the subepithelial surface. Over time, these deposits trigger spikes and holes visible under electron microscopy. While historically considered idiopathic, we now know that over 70% of cases involve autoantibodies against the PLA2R antigen—a major breakthrough enabling non-invasive diagnosis via blood testing. This subtype is strongly associated with nephrotic-range proteinuria and carries a variable prognosis: some patients experience spontaneous remission, while others progress to end-stage kidney disease without timely immunomodulatory intervention.

4. Focal Segmental Glomerulosclerosis (FSGS) — Patchy Scarring With Diverse Triggers

FSGS is marked by scarring (sclerosis) affecting only some glomeruli (focal) and only parts of those glomeruli (segmental). It's not a single disease but a histologic pattern with multiple causes—including genetic mutations, viral infections (e.g., HIV), obesity-related hyperfiltration, and circulating permeability factors. Primary (idiopathic) FSGS often shows rapid progression and high relapse rates post-transplant. Recent advances in genetic screening and anti-alpha-actinin-4 antibody testing are helping clinicians differentiate subtypes and select optimal therapies—from calcineurin inhibitors to novel monoclonal antibodies.

5. Membranoproliferative Glomerulonephritis (MPGN) — A Complex, Immune-Mediated Challenge

Once grouped under a single umbrella, MPGN is now understood as a spectrum of disorders driven by dysregulated complement activation—most commonly due to C3 glomerulopathy or immune-complex-mediated injury. It features both basement membrane thickening and mesangial hypercellularity, leading to a characteristic "double-contour" appearance on silver staining. Though rare (<5% of glomerulonephritis cases), MPGN tends to follow an aggressive course, especially in adults. New complement-targeting drugs (e.g., eculizumab, ravulizumab) are transforming outcomes—and highlighting the growing role of precision immunology in kidney care.

Taking Action: From Diagnosis to Personalized Care

If you or a loved one has been diagnosed with chronic glomerulonephritis, remember: your treatment plan should be as unique as your biopsy report. Don't settle for generic advice—seek care from a board-certified nephrologist experienced in interpreting renal pathology and managing complex glomerular diseases. Early, accurate subtyping isn't just academic—it's the foundation for slowing progression, preventing complications, and maintaining quality of life for years to come.