Merkus J W, van Asten W N, Hoitsma A J, van't Hof M A, Koene R A, Skotnicki S H
Department of Surgery, University Hospital St Radboud, Nijmegen, The Netherlands.
Clin Transplant. 1996 Oct;10(5):420-8.
Cyclosporin A (CyA) nephrotoxicity and rejection of a renal allograft each demands a specific therapy. This study was designed to establish the capability of Doppler spectrum analysis to diagnose either one of these causes during renal dysfunction. Between October 1989 and October 1991 we performed echo-Doppler examinations in 209 renal transplant recipients on a routine basis during the first three months after transplantation. Echo-Doppler examinations during periods of renal dysfunction were analyzed. A total of 93 periods of renal dysfunction, retrospectively due to rejection (n = 40) or CyA toxicity (n = 53), occurred in 70 patients during the study period. A control group consisted of 82 patients with normal functioning grafts. When compared to the control group, the Doppler features (in segmental arteries) of the rejection group showed significant lower frequency shifts [Fmax (Hz) 1637 +/- 423 vs. 1436 +/- 465; p < 0.05; Fdia (Hz) 582 +/- 180 vs. 458 +/- 225; p < 0.05], a shorter deceleration time of the Doppler spectrum [Tdown (ms) 340 +/- 100 vs. 276 +/- 102; p < 0.05], and a higher Resistance Index (RI 0.64 +/- 0.08 vs. 0.68 +/- 0.13; p < 0.05). Doppler spectra during CyA toxicity showed only a significantly longer acceleration time [Tmax (ms) 123 +/- 36 vs. 139 +/- 40; p < 0.05]. The capability of differentiation between the two causes was assessed with ROC analysis of single Doppler features, stepwise regression and canonic discriminant analysis on a set of Doppler features and with manual selection of several features with extreme values. ROC analysis yielded maximum sensitivity and specificity for the diagnosis of rejection using Tdown (sensitivity 65%; specificity 68%). Stepwise regression and canonic discriminant analysis of a set of features rendered a sensitivity and specificity of 73% and 64%, respectively. Explorative selection of extreme Doppler feature values showed that 18 of the 40 grafts with rejection had values that were only seen in 2 cases with CyA toxicity (positive predictive value 90%; sensitivity 45%; specificity 96%). In half of these cases Doppler features preceded the clinical diagnosis of rejection by a median of 4 d. In conclusion, Doppler spectra are influenced by rejection and CyA toxicity in specific ways. The Doppler features, however do not enable definite differentiation between rejection and CyA toxicity in all cases. Some changes in Doppler spectra are only seen in cases of rejection and thus enable positive identification of grafts with rejection, often earlier than clinical signs indicate rejection. A normal Doppler spectrum does not exclude rejection as the cause of renal dysfunction.
环孢素A(CyA)肾毒性和同种异体肾移植排斥反应均需要特定的治疗方法。本研究旨在确定多普勒频谱分析在肾功能不全期间诊断这两种病因中任何一种的能力。在1989年10月至1991年10月期间,我们对209例肾移植受者在移植后的前三个月进行了常规的超声多普勒检查。对肾功能不全期间的超声多普勒检查结果进行了分析。在研究期间,70例患者共出现93次肾功能不全,经回顾性分析,其中40次是由于排斥反应,53次是由于CyA毒性。对照组由82例移植肾功能正常的患者组成。与对照组相比,排斥反应组(节段动脉)的多普勒特征显示频移显著降低[最大频率(Fmax,Hz)1637±423对1436±465;p<0.05;舒张末期频率(Fdia,Hz)582±180对458±225;p<0.05],多普勒频谱减速时间缩短[下降时间(Tdown,ms)340±100对276±102;p<0.05],阻力指数升高(RI 0.64±0.08对0.68±0.13;p<0.05)。CyA毒性期间的多普勒频谱仅显示加速时间显著延长[最大加速时间(Tmax,ms)123±36对139±40;p<0.05]。通过对单个多普勒特征进行ROC分析、对一组多普勒特征进行逐步回归和典型判别分析以及手动选择几个具有极值的特征,评估了区分这两种病因的能力。ROC分析显示,使用下降时间诊断排斥反应时,敏感性和特异性最高(敏感性65%;特异性68%)。对一组特征进行逐步回归和典型判别分析的敏感性和特异性分别为73%和64%。对极端多普勒特征值进行探索性选择显示,40例发生排斥反应的移植物中有18例的值仅在2例CyA毒性病例中出现(阳性预测值90%;敏感性45%;特异性96%)。在这些病例中,一半的多普勒特征在排斥反应临床诊断前中位时间4天出现。总之,多普勒频谱以特定方式受排斥反应和CyA毒性影响。然而,多普勒特征并不能在所有情况下明确区分排斥反应和CyA毒性。多普勒频谱的一些变化仅在排斥反应病例中出现,因此能够在临床体征表明排斥反应之前就对发生排斥反应的移植物进行阳性识别。正常的多普勒频谱不能排除排斥反应是肾功能不全的原因。