Modulation of abnormalities in renal haemodynamics and vasoactive mediators by nifedipine in patients with psoriasis on low-dose cyclosporin

Ten patients with psoriasis received a 3-month course of cyclosporin(2.5 mg/kg/day) followed by a 3-month washout period, beforecommencing a 3-month course of cyclosporin and nifedipine SR20 mg b.d. Serial haemodynamic and biochemical measurementswere performed before, during, and after treatment. Total renalblood flow (RBF) was measured following an intravenous injectionof [^99mTc]-DTPA based on a renographic analysis of the first-passeffect in the kidneys, and GFR was estimated from the subsequentclearance of this radiotracer. A significant individual changein RBF or GFR was taken as 25/ and 20/ respectively. Simultaneousassays of the circulating vasoactive mediators renin, aldosterone,angiotensin II, and atrial natriuretic peptide were performed.Two patients withdrew from the study because they could nottolerate nifedipine, leaving eight for complete analysis. Thesignificant reductions in RBF and GFR which occurred on cyclosporinalone (P<0.05; ANOVA) did not occur with added nifedipine.Four months after this second course, RBF and GFR had recovered.The response to nifedipine was, however, variable and unpredictable.Of the four patients to show a significant decline in GFR oncyclosporin alone, only two showed a significant improvementon the combined therapy. Of the six patients who showed a significantdecline in RBF on cyclosporin alone, only four showed benefitfrom the added nifedipine. Nifedipine suppresses the increasein blood pressure which occurred on cyclosporin alone. The circulatingconcentration of angiotensin II was significantly less on cyclosporinand nifedipine than on cyclosporin alone (P<0.05; Student'st test). There was a significant reduction in serum aldosteroneafter cyclosporin administration (P<0.05; ANOVA). Plasmarenin activity did not change. There were statistically significantincreases in ANP on cyclosporin and nifedipine (P<0.05; ANOVA). The interaction between nifedipine and cyclosporin on the glomerularmicrocirculation and on the release of angiotensin II by thenormal innervated kidney can either reduce or increase haemodynamictoxicity. Regardless of haemodynamic improvement, nifedipinedoes not correct all the hormonal changes.