Dense Deposit Disease: A Rare Cause of Steroid Resistant Nephrotic Syndrome

Abstract

To the Editor: A 10-y-old boy presented with 1st episode of generalized anasarca, nephrotic-range proteinuria (4.55 g protein/ 24 h), hypoalbuminemia (serum albumin 2 g/dL), microscopic hematuria and hypertension [Blood pressure (BP)=118/80 mmHg; 95th centile-116/78 mmHg] for two wk. Family history was non-contributary. Eye examination was normal. Blood investigations revealed: serum creatinine 0.9 mg/dL (eGFR-100 mL/min/m), serum cholesterol 280 mg/dL, negative anti-nuclear and anti-neutrophilic cytoplasmic antibodies; low C3 levels-82 mg/dL (Normal: 90– 180 mg/dL); negative serology for hepatitis-B, hepatitis-C and human immunodeficiency viruses. A clinical possibility of membranoprolifrative glomerulonephritis was kept. Child was continued on prednisolone @2 mg/kg/d for four wk, which were later withheld due to severe hypertension. The child required enalapril, lasilactone, amlodipine for hypertension, and broad spectrum antibiotics. He developed hypertensive encephalopathy (max. BP-186/ 122 mmHg) and BP finally stabilised on labetalol and clonidine. He developed gross hematuria, anuria, deranged renal function (serum creatinine-3.5 mg/dL), and nephrosis persisted requiring supportive ventilation, blood transfusions and hemodialysis. Child had a progressive downhill course, and succumbed to end stage renal disease, fungal sepsis and multiorgan dysfunction. Parents refused autopsy. Postmortem renal biopsy samples after parental consent were sent for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). LM showed increased mesangial cellularity. Glomerular capillary walls showed eosinophillic and refractile thickening. Cellular crescents were present in 25 % of the glomeruli. (Figs. 1a,b) Tubular basement membranes did not reveal any thickening. IF revealed uninterrupted intense (3+) C3 deposits along the glomerular capillary loops, mesangium and the Bowman’s capsule (Fig. 1c). Direct IF for IgG, IgA, IgM, kappa and lambda light chains was negative. EM revealed highly osmophilic, discontinuous, dense deposits in the GBM (Fig. 1d). The LM, IF and EM findings were thus consistent with DDD (Dense Deposit Disease) [1, 2]. We could not try newer therapies e.g., plasmapheresis, eculizumab/rituximab, IVIG etc., as the diagnosis was available post-mortem [3, 4]. This re-emphasizes need for early biopsy in such cases [5]. V. Mahajan (*) :G. Jindal Department of Pediatrics, Government Medical College and Hospital, Sector 32, Chandigarh 160030, India e-mail: vidushimahajan2003@yahoo.co.in