EMBRANOUS glomerulonephritis, a major cause of the nephrotic syndrome and chronic renal insufficiency, is associated with a wide spectrum of infections, cancers, autoimmune diseases, and drugs. The condition is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane, but the target antigens have not been identified. Major contributions to our current understanding of the disease come from Heymann's nephritis, a rat model of membranous glomerulonephritis induced by immunization with an antigenic fraction of the renal brush border. 1 Studies of this experimental rat model led to the identification of megalin, a unique constitutive antigen expressed on the podocyte. 2,3 Although megalin has been found in human proximal tubules, it has not been found in human glomeruli or in immune deposits in patients with membranous glomerulonephritis. 4 Dipeptidyl-peptidase IV and neutral endopeptidase are two other antigens shared by the brush border and podocytes that are involved in the formation of immune deposits in animal models; these two proteins are expressed on the human podocyte. 5,6 In this article, we report that anti-neutral endopeptidase antibodies produced by a pregnant woman were transferred to her fetus, in which a severe form of membranous glomerulonephritis developed prenatally. The mother had a deficiency of neutral endopeptidase and probably had become immunized against the antigen at the time of or after an earlier miscarriage. CASE REPORTA male infant born at 38 weeks of gestation (birth weight, 3260 g; length, 50 cm) presented with oligoanuria (urine vol-M ume, 10 ml per 24 hours), massive proteinuria (Table 1), and respiratory distress on the first day of life. His parents were unrelated, healthy persons without a family history of renal or autoimmune disease. The mother, who was 24 years old, had had a miscarriage at 14 weeks of gestation 2 months before she became pregnant with this child. Her blood pressure, findings on urinalysis, and serum creatinine concentration were normal throughout and after the pregnancy, and she took no medications. However, antenatal ultrasonography showed oligohydramnios and enlarged fetal kidneys from the 34th week of gestation. The mother's level of antineutrophil cytoplasmic antibodies, antinuclear antibodies, anti-DNA antibodies, and complement were normal.Mechanical ventilation for hypoxemia was necessary from birth to 10 days. The infant's serum creatinine concentration was 1.9 mg per deciliter (170 µmol per liter) on day 2 and peaked at 2.7 mg per deciliter (240 µmol per liter) on day 4. Diuresis increased after the administration of intravenous furosemide. The serum creatinine concentration subsequently decreased, and nephrotic-range proteinuria developed (Table 1), as did hypoalbuminemia (1.9 g per deciliter on day 7). Calcium-channel blockers and beta-blockers were needed for blood-pressure control from day 5 until 6 weeks after birth. Urinary protein excretion progressively decreased to 4.2 mg per milligram of cr...

COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.

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