To evaluate the hypothesis that antibody-mediated damage to proximal tubules (PT) could be a feature of Heymann nephritis (HN), we studied the kidneys of rats in different stages of the disease by light, immunoflourescence (IF), transmission, and scanning electron microscopy. The observations of morphology were correlated with titers of circulating antibodies directed against the brush border (BB) and with proteinuria. Antibody titers reached a maximum 5 to 7 weeks after immunization with Fx1A, coincident with the onset of proteinuria. IgG and C3 were deposited along the BB of PT in all animals within the first week of proteinuria. BB antibodies were present in the urine of those rats. As antibody titers declined, a decrease in the extent of in vivo IgG deposition along the BB was also noted. The results of indirect IF tests, by using BB antibodies on kidneys of rats with HN of 3 to 4 months' duration, suggested extensive loss of the BB antigen(s) from the PT. Numerous granular deposits of IgG were present along the basement membrane of PT at that time. Study of kidney histology revealed that deposition of IgG and C3 along the BB of PT was associated with extensive loss of microvilli, as well as degeneration and proliferation of PT cells. Subepithelial electron-dense deposits were present along the basement membrane of PT. In rats with HN of more than 4 months' duration, with little or no circulating BB antibodies and persistent proteinuria, IgG and C3 were found in minimal amounts along BB. Examination by light and electron microscopy provided evidence of partial recovery of PT lesions in those kidneys. Rats with similar proteinuria resulting from chronic serum sickness did not have similar abnormalities of PT. These observations are consistent with the interpretation that, in rats with HN, BB antibodies induce cytotoxic injury to PT.

Interstitial immune complex nephritis in patients with systemic lupus erythematosus (SLE). Renal tissues from 45 patients with SLE nephritis, 34 patients with idiopathic membranous nephropathy (IMN) and 77 patients with minimal glomerular disease (MGD) were studied by light, immunofluorescence and electron microscopy. Interstitial nephritis characterized by focal or diffuse infiltration of inflammatory cells, tubular damage and interstitial fibrosis was observed in 66% of SLE patients. Fluorescein-conjugated antibodies to immunoglobulins or complement or both were bound to peritubular capillaries, interstitium and tubular basement membranes (TBM) in 53% of patients with a granular pattern corresponding to opaque deposits seen by light or electron microscopy or both. Antibodies reactive with thymidine or cytosine or both were bound to interstitial structures in 19% of patients tested and showed the same granular distribution. Interstitial cellular infiltration was rare and deposits of immunoglobulins and complement were rare or absent in IMN and MGD, whereas deposits of DNA products were never observed. The findings are consistent with the interpretation that in patients with SLE nephritis immune deposits, presumably containing DNA-anti-DNA complexes, localize in peritublular capillaries, TBM and interstitum, thereby producing an inflammatory reaction which contributes to development and evolution of renal diseases.

Spontaneously hypertensive rats (SHR) (N = 40) were maintained at normal blood pressure to the age of 100 weeks by treatment (reserpine, hydralazine, and chlorothiazide) beginning at intervals in groups of eight, from the 5th to 45th week. Mortality rates, patterns of proteinuria, and glomerular and arteriolar pathology were compared with that of treated and untreated normotensive Wistar-Kyoto (WKY) controls matched for age (N = 39) and untreated SHR's (N = 26). Treatment clearly prolongs life in SHR's, the mortality rate for untreated being 100% at 75 weeks versus no deaths at that age among 24 SHR's treated before 20th week. At 100 weeks, treated SHR's were excreting eight times the baseline values of urinary protein, whereas WKY's had hardly increased from baseline values. At 100 weeks, normotensive SHR's showed fibrinoid necrosis, sclerosis, and pericapsular fibrosis of glomeruli, whereas no morphologic damage was found in glomeruli or renal arterioles of WKY. Glomerular lesions in normotensive SHR's are indistinguishable in kind from their hypertensive counterparts, but occur somewhat later. Juxtamedullary glomeruli initially suffer the greatest damage and appear to be the major source of urinary protein. These findings speak against the hypothesis of an increased intravascular pressure as the major factor in the pathogenesis of arteriolar sclerosis and rather favor a genetic defect in the vascular system of the SHR, a defect strongly associated with the hypertensive trait. A possible relationship of this defect to inherited membrane abnormalities recently described in RBC and smooth muscle cells of SHR is discussed.

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The localization of angiotensin converting enzyme (ACE) in the gonads of the normal rabbit was studied by immunofluorescence and immunoelectron microscopy. The enzyme is present in the cytoplasm of testicular spermatids and of epididymal and ejaculated spermatozoa, and on the surface of follicular and tubal oocytes. These findings support the hypothesis that ACE has a role in gamete maturation and in fertilization.