Transformation of membranous into anti-GBM nephritis
A 50-year-old man was referred to our hospital 3 years ago with a history of bloody diarrhea along with central abdominal pain of colicky nature. The clinical examination was normal except for pallor and diffuse tenderness in the left flank. Investigations showed a hemoglobin of 16.3 g/ dL, WBC 10,700 (neutrophil count 51.9%, lymphocytes 22.5%, monocytes 8.2%, eosinophil 16.95%, basophil 0.5%), platelets 1,70,000/mm3, ESR 101 mm/h, blood sugar 90 mg/dL, urea 15.5 mg/ dL, creatinine 0.70 mg/dL, Na 136 meq/L, K 4.8 meql/L, and Cl 104 meq/L. Urinalysis showed a pH 5.8, protein +1, blood +3, Hb +3, RBCs 30, and no WBCs. Serology showed hepatitis HBsAg negative, hepatitis C antibody nonreactive, and schistosomal antibody titer 1:4196.\nThe patient had undergone a colonoscopy at a private hospital 1 week prior to visiting us, which reported the presence of schistosomal ova along with multiple polyps. Another colonoscopy at our hospital also gave the same results. Two of the polyps were resected and histopathology report confirmed the presence of tubulovillous adenoma with no evidence of malignancy. He was treated with oral praziquantel.\nA month later he was readmitted with pain in the left lumber region, which was dull and persistent in nature, with no history of blood in stool and no change in the color of urine. An examination showed a palpable left kidney with tenderness on deep palpation along with bilateral pedal edema. A kidney ultrasound also showed enlargement of both kidneys with no hydronephrosis. A computerized tomographic (CT) scan of the abdomen revealed left renal vein thrombosis and other laboratory findings were essentially as before.\nHis serology was done which showed ANA and Anti-ds DNA was negative; complement C3 1.6, C4 0.588, HepBsAg, and hepatitis C antibody were negative; factor V Leiden mutation negative; prothrombin mutation negative; protein C 75 (70- 140), protein S 55 (65- 140), anti-thrombin III 61 (80-120). VDRL negative, rheumatoid factor negative, anti-CCP antibody negative, Smith antibody negative, Sjögren A negative, and Sjögren B negative. Twenty-four hours urinary protein was 14 g.\nKidney biopsy showed 10 glomeruli, one of which was completely sclerosed, the remaining showed rigidity of the capillary wall []. There was no crescent formation or fibrinoid necrosis. Tubules and vessels showed no significant pathology, while interstitium showed mild mononuclear inflammatory cell infiltration and there was no significant fibrosis. Immunofluorescence study showed eight glomeruli with +3 granular membrane positivity with IgG and C3 and also there was focal 1+ positivity with IgM, while fibrinogen and IgA were negative. Electron microscopy showed subepithelial dense deposits []. All the results confirmed the diagnosis of membranous nephropathy.\nOral anticoagulant, prednisolone 30 mg with cyclosporin 150 mg twice a day was started. A follow-up colonoscopy was performed twice each 6 months apart that revealed adenomatous polyps with no evidence of malignancy. On follow-up after 6 months, he was stable with mild pedal edema, urea 35 mg/dL, creatinine 0.82 mg/dL, Na 139 meq/L, K 4.9 meq/L. Urinalysis showed protein +2, RBC nil, and 24-h urinary protein was 1.09 g, Cyclosporin was reduced to 50 mg BID and prednisolone to 5 mg OD.\nOn 1-year follow-up, the patient was found to be in complete remission, urea 18.6 mg/dL, creatinine 1.04 mg/ dL, Na132 meq/L, K 5.0 meq/L, and 24-h urinary protein 0.06 g; therefore, cyclosporine and steroids were discontinued.\nAfter 6 months of stopping all medications, he was stable, and urinary sediments showed no proteinuria or hematuria, and kidney functions were normal.\nTwo weeks after the last follow-up that was 2½ years after his first presentation, he was readmitted with a history of left lumbar pain and dark brown urine for 3 days. Examination showed diffused tenderness in the left lumbar region, blood pressure of 140/80, and pedal edema. On investigation, urinalysis showed blood 3+, protein 2+ with no cast, 24-h urinary protein was 5.0 g, urea 34 mg/dL, creatinine 3.42 mg/dL, Na 135 meq/L, K 5.5 meq/L, ANA negative, anti-DNA negative, and C3 and C4 normal cANCA negative.\nUltrasound and Doppler of the kidney were performed to rule out renal vein thrombosis, which revealed a normal size kidney and there was no evidence of renal vein thrombosis. He was started on oral prednisolone 60 mgs once a day.\nA kidney biopsy showed 24 glomeruli, of which three were globally obsolescent, seven showed cellular crescents, one showed fibrocellular crescent, two glomeruli showed segmental endocapillary proliferation, four showed fibrinoid necrosis in glomerular crescents [Figures and ] in the glomerular tufts. Silver stain showed moth-eaten appearance and spike formation. Approximately 20% of the specimen showed tubular atrophy and interstitial fibrosis. There was no vasculitis, thrombosis, or fibrinoid necrosis of blood vessels. The Congo red stain was negative.\nImmunofluorescence microscopic study showed diffuse granular capillary positivity with IgG 3+ and C3 1+, while IgA, IgM, C1q, and albumin were negative []. Electron microscopy examination showed diffuse effacement of the visceral epithelial cell foot process with widespread microvilli degeneration of the glomerular epithelial cell. The mesangium showed mild focal increase in mesangial matrix and cellularity; subendothelial or mesangial dense deposits were not seen [].\nSerology showed very high titer of anti-GBM antibodies, 190 u/mL. The patient was shifted to intravenous methylprednisolone and pulse cyclophosphamide and plasmapheresis were started. He showed progressive rise in serum creatinine with gradual decline in urinary output: hemodialysis was started due to volume overload and an impending pulmonary edema. Treatment continued on plasmapheresis, which was stopped after six sessions; pulse cyclophosphamide was given for 3 months and later on stopped due to persistent anuria.\nHe was put on maintenance hemodialysis three times a week. During hemodialysis, he was followed with a monthly titer of anti-GBM antibody that remained high for 4 months and gradually declined and disappeared after 6 months from the onset of anti-GBM disease. The schistosomal antibody titer was also followed which declined very slowly and the last titer was 1:1024, performed after three months of starting hemodialysis.