Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.

Abstract

Cyclosporine induces hypertension and widespread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n=37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172±4/108±2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427±245 dyne • s • cm" 5 • m" J in responders versus 2905 ±281 in nonresponders, P<.01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F la ) was suppressed below normal from 2468±323 ng/d before transplant to 1103±99 ng/d (P<.01) after transplant and did not change during nifedipine therapy. Urinary thromboxane Bj and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation. 1 The mechanisms underlying this disorder remain uncertain, although it is characterized by widespread vasoconstriction affecting systemic and regional vessels, including the kidney. The effects of antihypertensive medications on vascular regulation and kidney function after transplantation have not been clearly established. With the use of CSA, glomerular filtration is universally reduced after transplant. Studies in renal transplant recipients indicate that CSA produces intense renal vasoconstriction and loss of glomerular filtration rate (GFR) after each dose, which is associated with elevated urinary endothelin excretion. Calcium channel blocking agents, particularly dihydropyridines, ameliorate experimental nephrotoxicity from CSA 7 and prevent renal vasoconstriction. 8 They may improve GFR in some clinical settings, but this has not been widely examined in conditions other than renal transplantation.Previous results demonstrate that renal vasoconstriction after liver transplant in humans, unlike the rat, is associated with reduced vasodilating prostaglandins (prostacyclin). The relative ratio of thromboxane to From the Departments of Medicine and Transplantation Surgery, Mayo Clinic, Rochester, Minn.Correspondence to Stephen C. Textor, MD, Hypertension and Internal Medicine, Desk W9A, Mayo Clinic, Rochester, MN 55905.prostacyclin favors vasoconstriction. 6 We elected to examine monotherapy with nifedipine XL because of its capacity...

Posttransplantation Hypertension Related to Calcineurin Inhibitors

“…Under some circumstances, they appear to improve renal blood flow, although this has not been apparent during long-term therapy in liver transplant recipients. 64 Many have minor or negligible effects on blood levels of calcineurin inhibitors, although nicardipine may have major, unpredictable effects. Doses must be increased cautiously to limit edema, occasional vascular headaches, and symptoms of excess vasodilation in liver transplant recipients in whom cardiac outputs may remain elevated for several months after transplantation.…”

A randomized prospective crossover trial of amlodipine in pediatric hypertension

“…Calcium channel blockers are considered an ideal first-line agent for the treatment of post-transplantation hypertension [23,24,25] since they can partially counteract the renal vasoconstrictive effects of cyclosporine [26,27,28,29,30,31,32] and have been shown to mediate renal protection through various mechanisms [33].…”

Systemic hypertension in heart transplant recipients

“…Calcium antagonists are effective drugs in SH treatment in patients treated with cyclosporine 44,45 and seem to be the antihypertensives of choice 22,25,28,46 . Studies show that the early use of diltiazem (before, during or immediately after transplantation) is associated with a smaller incidence of episodes of rejection, as well as with a better function of the transplanted organ and a smaller incidence of coronary heart disease 22,46 .…”

“…Studies show that the early use of diltiazem (before, during or immediately after transplantation) is associated with a smaller incidence of episodes of rejection, as well as with a better function of the transplanted organ and a smaller incidence of coronary heart disease 22,46 . Calcium antagonists seem to have a protective effect on the kidney 27 , attenuating vasoconstriction produced by cyclosporine 28,38,47,48 , not increasing the glomerular filtration rate 22,45 , the renal plasmatic flow and the filtration fraction 22 . Experimental studies have shown that the same concentration that prevents the entrance of calcium into the renal tubule cells inhibits cyclosporine influx 49 .…”