Angiotensin II as a risk factor for cyclosporin nephrotoxicity in patients with psoriasis.
Abnormalities of the renin-angiotensin system after low-dose cyclosporin (5 mg/kg/day or less) have not been adequately defined in patients with normal kidneys. 27 patients with psoriasis were assessed before starting cyclosporin, after three months of cyclosporin (5 mg/kg/day or less) and then finally three months after finishing cyclosporin. On each occasion plasma renin activity (PRA), aldosterone, angiotensin II and atrial natriuretic peptide (ANP) were measured together with total renal blood flow (RBF), GFR and filtration fraction (FF) following an i.v. bolus injection of Tc-99m DTPA. Significant renal hemodynamic toxicity was defined as > 25% fall in RBF or > 20% fall in GFR. Using these criteria we identified 12 patients with hemodynamic toxicity (Group A) and 15 patients whose GFR and RBF did not fall significantly (Group B). In Group A a significant fall in GFR (p < 0.001) and reduction in renal blood flow (p < 0.04) were associated with significant rises in both ambulant and recumbent angiotensin II (p < 0.0005). PRA, aldosterone and ANP did not significantly alter. GFR partially recovered after withdrawal of cyclosporin although RBF remained significantly lower compared to initial values. In Group B there was no significant change in GFR or RBF although there was a reversible fall in FF (p < 0.02). There were no significant differences in angiotensin II, PRA, aldosterone or ANP. Circulating angiotensin II rises in patients who develop cyclosporin nephrotoxicity and may be responsible for mediating the hemodynamic effects.
Edwards
B D
BD
Department of Nephrology, Royal Infirmary, Manchester, UK.
Chalmers
R J
RJ
O'Driscoll
J B
JB
Mitchell
D M
DM
Smith
R J
RJ
Lawson
R S
RS
Testa
H J
HJ
Ballardie
F W
FW
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood*; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012307:Risk Factors
D000804:Angiotensin II; D016572:Cyclosporine