Factor H deficiency and fibrillary glomerulopathy

Abstract

A 12-month-old boy presented to a local hospital with periorbital oedema and microscopic haematuria. He was pale and hypertensive and had low serum complement C3. He was treated for and followed with the diagnosis of acute post-streptococcal glomerulonephritis. The patient’s parents were second-degree relatives of each other, but his family history was entirely negative for renal disease, hypertension and anaemia. When he was 17 months, he was referred to our unit for persisting haematuria and periorbital oedema. Physical examination revealed a pale, oedematous boy with a blood pressure of 180/90mmHg. His laboratory values included: urea 35mg/dl, creatinine 0.54mg/dl, albumin 4.3 g/dl, cholesterol 175mg/dl, haemoglobin 6.3 g/dl, MCV 77.7 fl, reticulosit count 0.52%. His platelet count was normal, and a peripheral blood smear showed no evidence of microangiopathy. The direct Coombs’ test was positive; the test for cold agglutinins was negative. Urinalysis revealed haematuria and proteinuria. Creatinine clearence (Ccr) was 122ml/min/1.73m 2 and the urine protein/ creatinine ratio was 3.76 (mg/mg). Tests for anti-nuclear and anti-glomerular basement membrane antibodies and anti-streptolysin O were negative. Serum C3 was 180mg/l (range 825–1140mg/l) and C4 was normal. C3 nephritic factor was negative. A renal biopsy and complement profiling were performed, and with the diagnosis of membranoproliferative glomerulonephritis (MPGN), the patient was treated with 0.5mg/kg/day oral enalapril and 2mg/kg/day oral prednisolone. His urine was protein free at the end of the first week, but he relapsed at the end of 1 month, when he was 18 months old. He now had: hypertension, proteinuria of 56.9mg/ m/h (protein/creatinine1⁄4 3mg/mg), Ccr of 120ml/min/ 1.73m, serum cholesterol of 242mg/dl, urea 53mg/dl, creatinine 0.3mg/dl, haemoglobin 9.2 g/dl and albumin 3.8 g/dl. He was treated with 30mg/kg doses of i.v. methyl prednisolone for 3 days, and afterwards with i.v. 500mg/m cyclophosphamide—monthly six times— and prednisolone 1.5mg/kg/day on alternate days. Enalapril was prescribed for hypertension. Microscopic haematuria and nephrotic-range proteinuria persisted over the 6 months of this therapy. He required hospitalization to control a sudden severe hypertensive crisis at the end of 6 months; and his blood pressure was regulated with 2mg/kg/day nifedipine, 25mg/day atenolol and 0.5mg/kg/day enalapril. Microhaematuria and nephrotic-range proteinuria persisted with high serum cholesterol, but he still had a normal Ccr. A second renal biopsy was performed at the age of 2.5 years. Cyclosporine A (CyA) at a dose of 5mg/kg was started, and alternate-day prednisone, nifedipine, enalapril and atenolol were continued. Serum cyclosporine levels were controlled against C0 and C2 levels. Cyclosporine doses were adjusted to maintain C0< 50ng/ml and C2 around 400 ng/ml. At the end of the second week, when C0 was 15 ng/ml and C2 was 434 ng/ml, urine protein began to decrease from the nephrotic-range, and microscopic haematuria disappeared. After 3 months of cyclosporine therapy, urine was protein-free and serum albumin and cholesterol normal; therefore, prednisolone and anti-hypertensive drugs were decreased gradually. CyA therapy was terminated at the end of 15 months of follow-up when he was 3.5 years old. He is still being followed-up, and has been on no medications for 6 months. His blood pressure, Ccr, serum cholesterol and serum albumin are at normal levels and his urine is protein-free; but he still has low complement—C3 (160mg/l). Correspondence and offprint requests to: Zelal Bircan, MD, Kocaeli Universitesi Tip Fakultesi Hastanesi, Cocuk Sagligi ve Hastaliklari Anabilim Dali, Derince/Kocaeli, Turkey. Email: [e-mail]