Severe functional and structural changes caused by lithium in the developing rat kidney.
Lithium (Li) was administered to rats during maternal pregnancy and/or 8 weeks post-natally, to study the effects on renal function and structure in the developing kidney. Plasma Li was 0.5-1.0 mmol/l 3 and 8 weeks post-natally. Functionally, post-natal Li leads to growth retardation, polyuria with lowering of renal concentration ability, and uremia associated with as much as 80% lowering of the normal glomerular filtration rate (GFR). Pre-natal Li alone did not affect the concentrating ability but caused a 20% increase in GFR when evaluated 8 weeks post-natally. Post-natal Li caused very severe structural changes, consisting of up to 3 mm cortical cysts (= dilated distal convoluted tubules), extensive interstitial fibrosis with cell infiltration, and atrophy of the cortical collecting ducts. Morphometric measurements showed a significant reduction in the volume of the proximal tubular cells. Pre-natal Li caused only slight structural changes, and animals treated both pre- and post-natally were less affected than animals treated post-natally only. The structural changes caused by post-natal Li were unrelated to changes in the concentrating ability but showed a significant correlation with the lowering of the GFR. It is concluded that the post-natally developing rat kidney is particularly sensitive to the nephrotoxic effects of Li, which in low concentrations causes impairment of renal function, leading to uremia. Pre-natal Li exposure by maternal lithium treatment had little effect on renal function and structure when evaluated post-natally.
D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D007671:Kidney Concentrating Ability / Q000187:drug effects; D007684:Kidney Tubules / Q000473:pathology; D008094:Lithium / Q000097:blood / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood; D014511:Uremia / Q000139:chemically induced
D014508:Urea; D008094:Lithium