Glomerulotubular function in cyclosporine A treated rats.
A total of 178 rats treated with Cyclosporine A (CyA, dose range 0-50 mg/kg/day) during 14 days were investigated with clearance methods (inulin, lithium, sodium and potassium), serum CyA and plasma renin concentration (PRC). Inulin clearance (Cin) decreased to a mean of 68% of the control value in the 12.5 mg/kg/day group, 44% in the 25 mg/kd/day group and 47% in the 50 mg/kg/day group, respectively. Lithium clearance (CLi) was reduced in all CyA treated groups, while the absolute proximal tubular reabsorption as calculated from Cin-CLi was decreased during increased fractional proximal reabsorption (1-CLi/Cin). As proximal intratubular hydrostatic pressure has been shown to be low in the normal range (excluding tubular obstruction) these findings are considered due to a decrease in ultrafiltration pressure. Furthermore we found the reabsorption of sodium distal to the proximal tubule to be decreased, both absolute (PNa X (CLi-CNa)) and fractional to the delivery from the end of the proximal tubule (1-CNa/CLi). Also the distal potassium reabsorption was decreased PK X (CLi-CK). These findings were not primary, but rather secondary, to the altered proximal function, since it has been shown that i.v. CyA immediately produces increased fractional proximal reabsorption. PRC was increased from a mean of 2.5 to 4.9 and 5.3 X 10(-4) Goldblatt units (GU)/ml (12.5 and 25 mg/kg group, respectively), to be explained by the decreased sodium delivery to the macula densa region and/or by a direct CyA effect. In conclusion CyA reduces the net ultrafiltration pressure, and due to an insufficient decrease in absolute proximal tubular reabsorption, fractional proximal reabsorption increases.(ABSTRACT TRUNCATED AT 250 WORDS)
Dieperink
H
H
Leyssac
P P
PP
Kemp
E
E
Steinbrückl
D
D
Starklint
H
H
D000818:Animals; D003524:Cyclosporins / Q000097:blood / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007444:Inulin; D007678:Kidney Glomerulus / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D007444:Inulin