Absence of acute nephrotoxicity with low doses of cyclosporin: experimental study in the rat.
No study has, to our knowledge, evaluated the acute effects of low immunosuppressive doses of cyclosporin (CsA) on renal function. To establish whether a relationship exists between the dosage of CsA and the onset of nephrotoxicity, 28 rats were studied by renal clearances before (control) and after i.v. administration of different doses of CsA: 3 mg/kg b.w. (group 1); 7 mg/kg b.w. (group 2); 11 mg/kg b.w. (group 3); 15 mg/kg b.w. (group 4). No change in renal function was observed between control and the post-CsA period in groups 1 and 2. GFR (inulin clearance) was decreased vs the control period in group 3 and group 4 (-22% and -37%, respectively, P less than 0.001); the difference between these two groups was statistically significant (P less than 0.01). Effective renal plasma flow (PAH clearance) was similarly decreased in groups 3 and 4 vs their control periods (-21% and -28%, respectively, P less than 0.001) due to the increase of total renal vascular resistance (+41% and +42%, respectively, P less than 0.001). Filtration fraction was significantly decreased by CsA in group 4 (P less than 0.01 vs the control period). PAH renal extraction, urinary volume, and sodium and potassium excretion were similar in all groups before and after CsA. PRA and ADH were significantly increased only in group 4 (P less than 0.01) vs the baseline values. A high and significant relationship was detected between CsA dosage and the decrease of GFR (r = 0.81, P less than 0.001) and RPF (r = 0.612, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Sabbatini
M
M
Department of Nephrology, 2nd Faculty of Medicine, University of Naples, Italy.
De Nicola
L
L
Uccello
F
F
Russo
D
D
Conte
G
G
Dal Canton
A
A
Andreucci
V E
VE
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003524:Cyclosporins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014667:Vasopressins / Q000097:blood
D003524:Cyclosporins; D014667:Vasopressins; D012964:Sodium; D011188:Potassium