Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.
Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Christensen
S
S
Department of Pharmacology, University of Copenhagen, Denmark.
Marcussen
N
N
Petersen
J S
JS
Shalmi
M
M
D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008094:Lithium; D008657:Metabolic Clearance Rate / Q000502:physiology; D009392:Nephrectomy; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
D004044:Dietary Proteins; D008094:Lithium