Atubular glomeruli, renal function and hypertrophic response in rats with chronic lithium nephropathy

Experimental lithium nephropathy was induced by administering lithium orally to newborn rats for 8 weeks; thereafter the rats were randomized into four groups which were studied after 8 weeks of further treatment. One group was left untreated, one group was given a high (40%) protein diet, one group was unilaterally nephrectomized and one group was unilaterally nephrectomized and received high protein diet after nephrectomy. Comparable control groups (not lithium-treated) were also studied. Stereological methods were used to estimate the total volume of different parts of the nephron, interstitial fibrosis, and the distribution of the volume of individual glomeruli. The structural integrity between the glomerulus and the proximal tubule was investigated on serial sections. No sclerotic glomeruli were present. The most extensive degree of hypertrophy with almost a doubling of the total volume of proximal and distal tubule cells was seen in the groups that were both nephrectomized and fed a high protein diet. In both controls and lithium-treated animals, high protein and nephrectomy induced enlargement of the glomerular tufts to volumes from 4 to 5 times the normal size. A pronounced heterogeneity of the glomerular population was found in the lithium-treated groups with 36-54% atubular glomeruli with small volumes, and 34-48% enlarged glomeruli connected to qualitatively normal proximal tubules. Only glomeruli connected to proximal tubules had a potential for hypertrophy. In multiple regression analysis the percentage of glomeruli connected to normal proximal tubules was correlated with the reciprocal of plasma creatinine, but the volume of fibrosis also contributed to the decreased renal function.