Lezanić V, Djukanović Lj, Marinković J, Blagojević-Lazić R, Radivojević D, Simić-Ogrizović S, Milutinović D, Borić Z, Djokić M, Krasojević-Kostić I, Marković V, Petrović M, Dujić A, Hadzi-Djokić J
Institute of Urology and Nephrology, Clinical Centre of Serbia, Belgrade.
Srp Arh Celok Lek. 2000 May-Jun;128(5-6):149-56.
Over the period 1980-1992 256 kidney transplantations were carried out in the Institute of Urology and Nephrology, Clinical Centre, Belgrade: 105 (41%) from cadaveric and 151 (59%) from alive related donors. The first kidney transplantation was performed in our Institution in 1974; however, in the first decade only 27 kidney transplantations were performed. Since 1987, thanks to an increasing number of living kidney donors, the number of transplantations continually increased, and after that period an average of 30 kidney transplantations are performed annually (Figure 1). The aim of the study was to establish the survival of patients and grafts, and factors influencing this survival, as well as to determine the causes of patients' death and graft loss. All the patients were followed-up in our outpatient department within at least 5 years to maximum 17 years. Drug combination therapies were changed in the observation period. From 1983 cyclosporin A (CyA) was added to azathioprine (Aza) and prednisolone (Pr). An increasing number of patients with high immunological risks necessitated the strongest initial immunosuppressive treatment with ALG in addition to Aza and Pr. CyA in a dose of 8 mg/kg b.w. was introduced when serum creatinine concentration fell below 300 mumol/L. The triple treatment including CyA, Aza and Pr was the most common maintenance immunosuppressive therapy in our patients.
One and five years survived 95% and 75% of patients, and 84% and 52% of grafts. In assessing the impact of donor source, the year of transplantation, and age of donors we obtained the following results: Living related grafts survived better than cadaver grafts, especially during the first posttransplantation year (Figure 2). Furthermore, graft survival rates from 1987 to 1992 were significantly better than those from early period i.e. 1980 to 1986 (Figure 3). The significantly worse survival rate for grafts from donors older than 60 was noted than for grafts from younger donors. Searching for factors influencing the survival, non immunological and immunological differences between donors and recipients were analyzed. Our analysis showed that 50 living related donors were older than 60. In addition, the majority of them were 20 years older than their graft recipients. Two and more HLA mismatches were observed in 46% of our transplant patients, and 20 patients were highly sensitized. However, the immunological risks were higher in living related transplantations: different ABO blood groups, historical positive cross match reaction between donors and recipients (Table 1). A multivariate analysis using Cox proportional hazards model was performed to determine the important independent predictors of graft survival, and it revealed the following factors (Table 2): number of acute rejections, graft function at the end of the first month and until the end of the first posttransplant year, donors' age, and age and sex differences between donors and recipients. The occurrence of acute rejection at any time had a significant negative effect on graft survival. Since better HLA matching is likely to mean less early rejection it could be concluded that HLA matching influenced graft function and survival in our patients. Absence of acute rejection and delayed graft function or acute tubular necrosis were associated with an improvement of the graft function based on serum creatinine concentration, indicating that delayed graft function also influenced graft survival. The relative risk of graft loss was 2 times higher for patients receiving graft from donors older than 60. Until December 1997, when our analysis was done, of 256 kidney transplant patients 156 lost their grafts. The major causes of graft loss (Table 3) in the early period from 1980 to 1986 were non immunological such as acute tubular necrosis, vascular thrombosis and patients death with functioning graft. (ABSTRACT TRUNCATED)
1980年至1992年期间,贝尔格莱德临床中心泌尿外科和肾病研究所进行了256例肾移植手术:105例(41%)来自尸体供体,151例(59%)来自活体亲属供体。我们机构于1974年进行了首例肾移植手术;然而,在第一个十年里仅进行了27例肾移植手术。自1987年以来,由于活体肾供体数量增加,移植手术数量持续上升,此后每年平均进行30例肾移植手术(图1)。本研究的目的是确定患者和移植物的存活率、影响该存活率的因素,以及确定患者死亡和移植物丢失的原因。所有患者在我们的门诊部接受了至少5年至最长17年的随访。在观察期内药物联合治疗发生了变化。从1983年起,将环孢素A(CyA)添加到硫唑嘌呤(Aza)和泼尼松龙(Pr)中。越来越多具有高免疫风险的患者除了使用Aza和Pr外,还需要使用抗淋巴细胞球蛋白(ALG)进行最强的初始免疫抑制治疗。当血清肌酐浓度降至300μmol/L以下时,引入剂量为8mg/kg体重的CyA。包括CyA、Aza和Pr的三联治疗是我们患者中最常见的维持性免疫抑制治疗。
患者1年和5年生存率分别为95%和75%,移植物1年和5年生存率分别为84%和52%。在评估供体来源、移植年份和供体年龄的影响时,我们得到了以下结果:活体亲属移植物的存活情况优于尸体移植物,尤其是在移植后的第一年(图2)。此外,1987年至1992年的移植物存活率明显优于早期,即1980年至1986年(图3)。供体年龄大于60岁的移植物存活率明显低于年轻供体的移植物。为寻找影响存活的因素,分析了供体和受体之间的非免疫和免疫差异。我们的分析显示,50例活体亲属供体年龄大于60岁。此外,他们中的大多数比其移植物受体大20岁。在46%的移植患者中观察到2个及以上HLA错配,20例患者高度致敏。然而,活体亲属移植中的免疫风险更高:供体和受体之间ABO血型不同、历史阳性交叉配型反应(表1)。使用Cox比例风险模型进行多变量分析以确定移植物存活的重要独立预测因素,结果显示了以下因素(表2):急性排斥反应的次数、第一个月末直至移植后第一年年底的移植物功能、供体年龄以及供体和受体之间的年龄和性别差异。任何时候发生急性排斥反应对移植物存活都有显著的负面影响。由于更好的HLA配型可能意味着早期排斥反应更少,可以得出结论,HLA配型影响了我们患者的移植物功能和存活。无急性排斥反应以及移植物功能延迟或急性肾小管坏死与基于血清肌酐浓度的移植物功能改善相关,表明移植物功能延迟也影响移植物存活。接受年龄大于60岁供体移植物的患者移植物丢失的相对风险高出2倍。截至1997年12月我们进行分析时,256例肾移植患者中有156例失去了他们的移植物。1980年至1986年早期移植物丢失的主要原因是非免疫性的,如急性肾小管坏死、血管血栓形成以及有功能移植物的患者死亡。(摘要截断)