Prognosis and treatment of membranous nephropathy

C. Ponticelli

Research output: Contribution to journalArticle

Abstract

A 52-year-old man was admitted to the Nephrology Division of the Ospedale Maggiore of Milan for investigation of the nephrotic syndrome. He had been well until one year before, when he began to notice peripheral edema. After some weeks he consulted a physician, who obtained the following laboratory data: plasma creatinine, 1.0 mg/dl; BUN, 10 mg/dl; total serum protein, 5.4 g/dl; urinary protein, 5 g/24 hours; and microhematuria. A renal biopsy was recommended, but the patient refused. Hydrochlorothiazide, 50 mg daily, was prescribed. The edema worsened over the succeeding months and became resistant to progressively higher doses of diuretic agents. At admission, the temperature was 36.2 °C; pulse, 90; respirations, 18/min; and blood pressure, 160/100 mm Hg. The patient appeared to be well. No lymphadenopathy was present. The head and neck were normal. Rales were heard over the lower third of both lung fields. The cardiac examination and peripheral pulses were normal. Abdominal examination revealed evidence of ascites. There was marked edema over the sacral area as well as below the knees. Plasma creatinine was 1.3 mg/dl; BUN, 25 mg/dl; hematocrit, 44% white blood cell count, 8,000/mm3 with a normal differential; platelet count, 290,000/mm3; plasma sodium, 132 mEq/liter; potassium, 3.2 mEq/liter; and chloride, 98 mEq/liter. The erythrocyte sedimentation rate was 30 mm/hr. The total serum protein was 4.8 g/dl; albumin, 2.5 g/dl; cholesterol, 480 mg/dl; triglycerides, 330 mg/dl; calcium, 7 mg/dl; phosphorus 3.1 mg/dl; and uric acid, 5 mg/dl. Fasting and postprandial blood glucose values were normal. The urine had a specific gravity of 1.018; pH, 5.6; 4+ protein; and no glucose. Red blood cells and numerous hyaline and granular casts with lipid inclusions were found in the sediment. Urine culture was negative. A 24-hour urine collection contained 8 g of protein. Chest X-ray was normal. An intravenous urogram and a sonogram revealed two kidneys of normal size with no evidence of obstruction. The total hemolytic complement activity was 180 U (normal, 150 to 250 U); C3 was 120 and C4 35 mg/dl. Serologic tests for rheumatoid factor, syphilis, cryoglobulins, and anti-dsDNA antibodies were negative. A renal biopsy was performed. On light microscopic examination, 2 obsolescent and 10 patent glomeruli were identified. The glomerular capillary walls were diffusely and homogeneously thickened. Staining with trichrome acid fuchsin orange G demonstrated that some capillary loops contained many fine granular protein deposits in an epimembraneous position. Silver methenamine stain showed 'spikes' over the outer part of the basement membrane of some loops. Tubular structures were well preserved. Slight focal interstitial fibrosis and mild arteriolar sclerosis were present. Electron microscopy disclosed subepithelial osmiophylic deposits that were separated by spikes in some areas and which were completely incorporated into the basement membrane in others. The epithelial cells contained many protein droplets and showed extensive fusion of foot processes. No virus-like particles were observed. Slight mesangial sclerosis also was present but no mesangial deposits were seen. Immunofluorescence studies demonstrated diffuse, fine granular IgG deposits distributed homogeneously along the capillary walls in all glomeruli; C3 was deposited in a similar but fainter pattern. A diagnosis of membranous nephropathy was made.

Original languageEnglish
Pages (from-to)927-940
Number of pages14
JournalKidney International
Volume29
Issue number4
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Nephrology

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