Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DB A-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.

No abstract

5 cases with the compatible serological criteria of mixed connective tissue disease described earlier are presented. In 1 of them with a moderate degree of proteinuria, the renal biopsy disclosed membranous nephritis. However, despite the absence of overt clinical renal disease in the other 4 cases, biopsies disclosed membranous nephritis in 1 and mild mesangial proliferative glomerulonephritis in the remaining 3 cases. In the follow-up of these 4 cases, 2 subsequently developed abnormal urinalysis. Electron microscopic examinations demonstrated electron-dense deposits in glomeruli, and 4 of these patients also had microtubular structures in the endothelial cytoplasm. Contrarily to the original concept, our findings suggest that mixed connective tissue disease also induces immune complex disease.

Gentamicin (GM) often causes polyuric acute renal failure (ARF) in humans and animals. GM-mediated ARF in rats was accompanied with activated renin-angiotensin system, increased renal endothelin content, and enhanced lipid peroxidation. Suppression of the renin-angiotensin activity by desoxycorticosterone acetate and saline drinking, and treatment with superoxide dismutase attenuated the GM-induced decline in whole-kidney GFR with well-maintained RBF but did not reduce the severity of tubular necrosis. On the other hand, treatment with dimethylthiourea, a hydroxyl radical scavenger, attenuated the GM-mediated decline in GFR and lessened tubular necrosis but did not ameliorate the reduction in RBF. These data suggest contributions of both vascular and tubular factors to the GM-induced decline in GFR in rats. However, relative importance of these factors probably differs with different doses of the agent.

Nephrosis was induced by single injections of puromycin of aminonucleoside to rats which were divided into two groups; the experimental group receiving dipyridamole in addition to aminonucleoside and the control group receiving aminonucleoside alone. 24-hour urinary albumin increased in rats of both groups after aminonucleoside injections. However, the experimental rats excreted significantly less albumin than controls. On the contrary, there was no significant difference in urinary IgG between the two groups. The stainings of anionic sites of glomerular basement membrane using ruthenium red revealed the reduction of anionic charge in the glomerular basement membrane of both groups, but the decrease of anionic charge was suppressed in lamina rara interna of the experimental rats. Considering the role of charge barrier in the glomerular basement membrane, it is concluded that the maintenance of anionic charge in experimental rats is causally related to the suppressed excretion of albumin.