Glomerular Chaos: Diffuse Proliferative Glomerulonephritis in CKD

Introduction: Diffuse proliferative glomerulonephritis (DPGN) is a kidney disorder characterized by the activation of the alternative complement pathway, often associated with infection-related and C3 deposits. The clinical outcomes and onset of DPGN are variable and may include complete recovery, progression to chronic kidney disease, or advancement to end-stage renal disease. Case Description: A 74-year-old man with diabetes, hypertension, and stage 3 chronic kidney disease (baseline creatinine 1.8 mg/dL) presented with weakness. Labs showed mild renal impairment (creatinine 2.0 mg/dL), elevated CPK, BNP, WBC, and normal lipid profile, HbA1c, and lactate. Blood cultures grew methicillin-sensitive Staphylococcus aureus, and he was treated with IV oxacillin. Initially stable, his creatinine rose to 7.6 mg/dL with oliguria and uremic symptoms, requiring dialysis. Urinalysis showed proteinuria, hematuria, and glucosuria. Oxacillin-induced acute interstitial nephritis was suspected, and steroids were started. However, serologies were negative, and kidney biopsy revealed C3-dominant, infection-associated diffuse proliferative glomerulonephritis with acute tubular necrosis, not interstitial nephritis. Discussion: DPGN with infection-associated C3 deposits is characterized by diffuse involvement of most glomeruli, proliferation of mesangial and endothelial cells, and prominent deposition of C3 complement within the glomeruli. This condition is most commonly linked to Group A Streptococcus, Staphylococcus aureus infections, Escherichia coli, and Pseudomonas species; viral and fungal causes are less common. DPGN typically affects children, young adults, and the elderly, with a male predominance and a higher incidence in underserved populations. Prognosis is generally worse in individuals with underlying comorbidities like diabetes mellitus, autoimmune diseases, or pre-existing chronic kidney disease. Histological findings such as crescent formation on kidney biopsy and a lower estimated glomerular filtration rate at diagnosis are also associated with poorer outcomes. Prompt and effective treatment of the underlying infection is crucial for preventing progression of the glomerulonephritis. Early diagnosis and targeted therapy help resolve the primary infectious cause and minimize renal damage, improving long-term outcomes and preserving kidney function.