Zietse R, van Ierland-van Leeuwen M L, Derkx F H, Ijzermans J N, Schalekamp M A, Weimar W
Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Am J Kidney Dis. 1994 Dec;24(6):927-31. doi: 10.1016/s0272-6386(12)81063-8.
The renal side effects are the major limitation of the use of cyclosporine in clinical transplantation. We studied the reversibility of changes in renal hemodynamics and glomerular barrier function in 17 patients with moderately impaired renal function at least 1 year after kidney transplantation. All patients were studied both during cyclosporine treatment and 3 months after conversion to azathioprine. During azathioprine treatment both glomerular filtration rate and effective renal plasma flow increased significantly (from 44.3 +/- 4.2 mL/min to 63.5 +/- 5.4 mL/min and from 192 +/- 12.8 mL/min to 260 +/- 14.6 mL/min, respectively). Despite the marked changes in renal hemodynamics, no significant changes were observed in the fractional clearances of uncharged dextrans. When calculating the characteristics of the filtration barrier, we observed a trend toward an increase in the ultrafiltration coefficient (Kt). This trend was abolished when an increase in net filtration pressure (delta P) was assumed to result from reduced prerenal vasoconstriction. We conclude that despite marked improvement of renal perfusion and glomerular filtration, conversion from cyclosporine to azathioprine did not significantly alter the permeability characteristics of the glomerular filtration barrier in renal transplant recipients with moderately reduced renal function. Improvement in renal function following conversion could result from an increase in either Kf or delta P. Since renal plasma flow was increased significantly, the observed improvement in glomerular filtration rate is likely to be, at least in part, due to an increase in glomerular capillary plasma flow.
肾毒性副作用是临床移植中使用环孢素的主要限制因素。我们研究了17例肾功能中度受损的肾移植患者在肾移植至少1年后肾血流动力学和肾小球屏障功能变化的可逆性。所有患者在接受环孢素治疗期间以及转换为硫唑嘌呤治疗3个月后均接受了研究。在硫唑嘌呤治疗期间，肾小球滤过率和有效肾血浆流量均显著增加（分别从44.3±4.2 mL/min增至63.5±5.4 mL/min以及从192±12.8 mL/min增至260±14.6 mL/min）。尽管肾血流动力学发生了显著变化，但未观察到中性葡聚糖分数清除率有明显改变。在计算滤过屏障的特征时，我们观察到超滤系数（Kt）有增加的趋势。当假定肾前血管收缩减弱导致净滤过压（ΔP）升高时，这种趋势消失。我们得出结论，尽管肾灌注和肾小球滤过有显著改善，但对于肾功能中度降低的肾移植受者，从环孢素转换为硫唑嘌呤并未显著改变肾小球滤过屏障的通透性特征。转换后肾功能的改善可能是由于Kf或ΔP增加所致。由于肾血浆流量显著增加，观察到的肾小球滤过率的改善至少部分可能是由于肾小球毛细血管血浆流量增加所致。
