Hereditary Nephritis: Early Clinical, Functional, and Morphological Studies

Abstract

ExtractThe accumulation of literature on hereditary nephritis with or without nerve deafness attests to the increased awareness of the existence of this syndrome. I t is the purpose of this report to show that there are distinguishing histologic findings in young patients with minimal disease and normal renal function. Eleven patients were studied; 4 were females and 7 were males. Relevant family histories and clinical laboratory findings are shown in table I. I n all patients, hematuria, gross or microscopic, was present. Exacerbations of the hematuria occurred as a part of the exaggerated response of these patients to upper respiratory infection. Renal functional data are shown in table 11. These data were generally within normal limits for our laboratory. Table I11 outlines the morphologic findings observed on renal biopsy. In renal biopsies obtained from 10 patients, there was observed persistence of fetal-like glomeruli characterized by the circumferential crowding of visceral epithelium and an apparent decrease in the number of patent capillaries. The most striking finding in the tubules was the presence of red cells and red blood cell casts seen mainly in the distal and collecting tubules. Foam cells were an infrequent finding but, when present, were unassociated with interstitial fibrosis. Examination of kidney specimens under the electron microscope revealed the presence of at least three glomeruli in seven patients and of fetal-like glomeruli in all patients. There was also circumferential crowding of visceral epithelial cells, particularly at the surface, facing Bowman's capsule. These epithelial cells were characterized by large nuclei, small amounts of cytoplasm, apparently poorly developed intracytoplasmic organelles, and frequent villous-like cytoplasmic projections on the surface. I n families from whom past histories are unavailable, recognition of distinct renal biopsy characteristics would help identify this syndrome in the early stages of disease. At this stage, the combination of morphologic features considered to be characteristic would include the presence of a) fetal-like glomeruli, which were seen by electron microscopy in 7 patients and by light microscopy in 10 patients; b) mild to moderate hypercellularity ; c) large numbers of tubules filled with red blood cells and red blood cell casts; and d) foam cells in the absence of interstitial fibrosis. The fetal-like glomeruli present in our patients did not correspond to any of the normal stages of glomerular development observed under electron microscopy by other investigators, but rather, appeared to represent dysgenesis. Most patients from whom data are reported were more than 2 years of age, at which time fetal glomeruli are exceptional. Of interest was the observation that almost identical histology was found to exist among the siblings. ANTONOVYCH, DEASY, TINA, D'ALBORA, HOLLERMAN a n d CALCAGNO SpeculationT h e fetal-like glomeruli observed o n renal biopsy might b e the result of either a developmental abnormality or dysgenesis. T ...

Hereditary Nephropathy with Nerve Deafness (Alport’s Syndrome)

“…This ultrastructural lesions seems to be a peculiar hallmark of Alport's syndrome. The characteristic lesions of podocytes that we observed have already been described [1,17].…”

Hereditary Interstitial Nephritis without Basement Membrane Changes

“…Patients with a hereditary nephritis, such as Alport's syn drome, usually present with hematuria [5][6][7] and this may even be present at birth [8]. In fact, Gubler et al [2] have reported in their experience that microscopic hematuria, with or without associated proteinuria, is the first indication of the disease.…”

The Alport nephropathy: clinicopathological correlations

“…Further reports [6,7] emphasized GBM thickening as the earliest recognizable change in hereditary nephritis. The recognition of these ultrastructural GBM changes as specific to AS followed in 1972 in detailed descriptions by Spear and Slusser [8] and Hinglais et al [9], confirmed a year later by Churg and Sherman [10].…”