Acute effect of CyA A (Neoral®) on large artery hemodynamics in renal transplant patients

Abstract

CyA A (CyA) may induce intrarenal vasoconstriction, endothelial dysfunction, and hypertension. There are only two contradictory reports describing the acute effect of CyA on renal resistances measured by color Doppler flowmetry. Therefore, we studied the acute influence of oral CyA on arterial haemodynamics by assessing simultaneous changes in blood pressure, applanation tonometry-derived pulse wave analysis and duplex ultrasound-derived intrarenal resistance indices. Augmentation index (AIx) (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse pressure = AIx) was determined from contour analysis of arterial waveforms recorded by applanation tonometry using the AtCor device in 18 live-related renal transplants (11 females/7 males, age = 32.0 +/- 8.1 years, transplantation duration = 17.5 +/- 16.1 months, and mean serum creatinine = 133 +/- 70 micromol/L). All studies were performed just before (C0), and 2 hours after (C2) the oral administration of CyA. At the same C0 and C2 moments the resistive index (RI) = (peak systolic frequency shift - minimum diastolic frequency shift)/peak systolic frequency shift, and pulsatility index (PI) = (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift were calculated from Doppler recorded waveforms. Blood pressure and heart rate did not differ significantly at C0 and at C2 serum levels: 134.3/82.9 vs. 128.1/80.0 mm Hg and 72.0 vs. 71.0 beats/min, respectively, despite a marked increase in whole blood concentration (CyA(C0)= 90.8 +/- 45.9 vs. CyA(C2)= 547.4 +/- 251.3 ng/mL) (P= 0.05). Mean AIx fell significantly from 17.2 +/- 13.8 to 12.9 +/- 14.2 (P < 0.0001). There was no correlation between the extent (expressed as absolute or relative change) of the measured alteration in AIx and total administered CyA dose, or increment in blood level between C0 and C2. In support, the intake of CyA did not induce a significant increase in Doppler resistance (RI(C0)= 0.68 +/- 0.08 vs. RI(C2)= 0.70 +/- 0.09) and pulsatility indices (PI(C0)= 1.32 +/- 0.31 vs. PI(C2)= 1.33 +/- 0.28). Finally, three patients were studied twice (>1 week): one under two levels of creatinine, one with no antihypertensives, and a third receiving verapamil initially. All these maintained a significant decrease in AIx at C2 from C0 supporting the reproducibility of the phenomenon. We demonstrate that Neoral CyA acutely improves large arterial compliance function and does not induce an acute rise in intrarenal resistance in stable renal transplant subjects with normal renal function. We speculate that there may be an effect of vitamin E, the diluent vehicle in which CyA is carried (1000 IU/100 mg CyA), shown to improve endothelial function.