Glomerular hemodynamics in cyclosporine nephrotoxicity following uninephrectomy.
Experiments were performed to determine the cause of the reduced glomerular filtration rate (GFR) in cyclosporine nephrotoxicity during compensatory renal growth. Sprague-Dawley rats were uninephrectomized and given daily injections of cyclosporine (30 mg/kg, i.m.) or vehicle (olive oil), and studied 7 or 14 days later. In cyclosporine treated rats GFR was lower seven days (1.34 +/- 0.10 vs. 1.68 +/- 0.07 ml/min) and 14 days (1.19 +/- 0.08 vs. 1.58 +/- 0.04, P less than 0.025) following uninephrectomy. Arterial blood pressure, cardiac output and renal blood flow (RBF) were not different in cyclosporine and control rats. Kidney mass increased to the same extent in cyclosporine and control rats. Micropuncture of the glomerular microcirculation in similarly prepared Munich-Wistar rats demonstrated low whole kidney GFR (1.10 +/- 0.07 vs. 1.55 +/- 0.13 ml/min, P less than 0.01), and single nephron GFR (31.07 +/- 2.27 vs. 42.36 +/- 2.47 nl/min, P less than 0.005) in cyclosporine treated rats as compared to controls. Single nephron plasma flow, afferent and efferent arteriolar resistance, the transglomerular hydrostatic pressure gradient, and arterial blood pressure were the same in both groups. The glomerular capillary ultrafiltration coefficient (Kf) was lower in cyclosporine treated rats compared to controls [0.039 +/- 0.002 vs. 0.075 +/- 0.013 nl/(sec.mm Hg), P less than 0.025]. We conclude that in this model of cyclosporine nephrotoxicity the low GFR is caused solely by a reduction in Kf, and that cyclosporine can reduce GFR without causing renal vasoconstriction.
Winston
J A
JA
Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Feingold
R
R
Safirstein
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003524:Cyclosporins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*
D003524:Cyclosporins