Glomerular structure in lithium-induced chronic renal failure in rats

The effects of long-term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were stud ied in rats. Male Wistar rats were fed a lithium-containing diet (Li) or co ntrol diet (C) for 16 weeks postnatally. Li-treated rats developed renal fa ilure, hypertension and proteinuria. During the subsequent 24 weeks, subgro ups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerula r characteristics by light microscopy. Mesangial and mesangial matrix volum e fractions, surface density of capillary walls, basement membrane thicknes s and foot process width (FPW) were measured by electron microscopy. Glomer ular volume was decreased in Li-rats, with increased intra-individual varia tion. In all Li-rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systemat ic sampling of three glomeruli in each rat showed no differences among grou ps. Among Li-treated animals there was a significant correlation between FP W and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long-term lith ium administration to newborn rats caused marked changes in glomerular volu me which were not associated with measurable changes in structural paramete rs. No effect of ACEI-treatment was detectable.