Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine

In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time posttransplantation than Aza/P-treated patients (P<0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 mol/l per year for Aza/P-treated patients and 2.4 mol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m²/year in the Aza/P group and 1.07 ml/min per 1.73 m²/year in the CyA/P group (P=0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used. Thus, these data do not indicate a progression with time of the nephrotoxicity observed in CyA-treated patients.     

Renal allograft immunosuppression

A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidnery allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n=12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81%, 88%, 88%, and 88%, respecively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 mol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3.5–4.2 mg/kg per day and CyA concentrations were equal.     

Renal allograft immunosuppression III. Triple therapy versus three different combinations of double drug treatment: two year results in kidney transplant patients

A prospective randomized trial was carried out to compare the long-term effects of triple therapy based on low-dose cyclosporin A (CyA), low-dose methylprednisolone (MP) and azathioprine (Aza) with three different double drug immunosuppressive regimens. After initial triple drug immunosuppression for 10 weeks, 128 patients were randomized into four different immunosuppressive groups: one group continued with triple therapy (group A) and the three other groups were treated with different combinations of two drugs: Aza and CyA (group B), Aza and MP (group C) and CyA and MP (group D). This report presents the 2-year results. For groups A, B, C and D, graft survivals were 75%, 78%, 84% and 81%, respectively, and patient survivals were 84%, 84%, 84% and 94%, respectively. After 2 years no patient had returned to dialysis in group C compared with one to three patients in every CyA-using group. However, at the end of the 2nd year, group C included more patients with deteriorating graft function than the other groups. Median serum creatinine was 107, 120, 139 and 129 mol/l for groups A, B, C and D, respectively. For the patients who remained on the original randomized protocol, there were no significant differences in graft function tests between the four groups, the median creatinine being 115, 115, 118 and 113 mol/l for groups A, B, C and D, respectively. Thus, no graft deterioration had occurred during the 2 years for these patients following the original protocol. Our results suggest that after initial triple therapy, patients with a first cadaveric kidney allograft can either continue with triple therapy or be converted to any of the double drug regimens without detriment to graft function, graft survival or patient survival for the next 2 years. This will allow more flexible and individual immunosuppressive treatment.     

Renal allograft immunosuppression

Serum lipid and lipoprotein profiles were performed in order to investigate lipid abnormalities 2 years post-transplantation in first cadaveric renal allograft recipients immunosuppressed with cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), or with any combination of two drugs. CyA was used in low doses. Total serum cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1, and apolipoprotein B were determined in 88 prospectively randomized patients with functioning grafts. When considering only the patients who remained on the original randomized treatment, there were no significant differences between the four groups in any of the measured variables. Mean total cholesterol was highest in the group receiving Aza and MP (6.8 mmol/l) and lowest in the group receiving triple therapy (5.8 mmol/l; NS). Mean triglyceride level was highest in the group receiving Aza and MP (2.3 mmol/l) versus 1.8–2.2 mmol/l in the groups receiving triple therapy, Aza+CyA, and CyA+MP. For all patients mean triglyceride level was highest in the group receiving Aza and MP (2.7 mmol/l) and lowest in the group receiving triple therapy (1.7 mmol/l; P<0.05). Mean HDL cholesterol ranged from 1.5 to 1.6 mmol/l in all groups. Neither CyA concentration nor CyA or MP dose correlated with cholesterol or triglyceride concentration. However, the average MP dose was twice as high in the group receiving Aza and MP as in the other two groups employing steroids. Serum cholesterol and triglyceride concentrations were related to body mass index (r=0.28, P=0.045 and r=0.30, P=0.029, respectively). Hyperlipidemia was most common in the group receiving Aza and MP. The frequency of hypercholesterolemia (serum cholesterol level >6.5 mmol/l) was 18%, 45%, 60%, and 35% for the patients continuing with the originally randomized treatment in the groups receiving triple therapy, Aza+CyA, Aza+MP, and CyA+MP, respectively. In a normal Finnish reference population, 35% of all males and 31% of all females have a serum cholesterollevel above 6.5 mmol/l. Thus, only patients receiving Aza and MP had a clearly higher frequency of hypercholesterolemia than that found in a normal population. Taken together, this study shows no lipid abnormalities associated with the use of low-dose CyA for 2 years after transplantation. Hyperlipidemia occurring after transplantation is probably multifactorial and more associated with other risk factors than with the immunosuppressive therapy.     

Renal allograft immunosuppression: IV. Comparison of Iipid and lipoprotein profiles in blood using double and triple immunosuppressive drug combinations

Abstract. Serum lipid and lipoprotein profiles were performed in order to investigate lipid abnormalities 2 years post-transplantation in first cadaveric renal allograft recipients immunosuppressed with cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), or with any combination of two drugs. CyA was used in low doses. Total serum cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1, and apolipoprotein B were determined in 88 prospectively randomized patients with functioning grafts. When considering only the patients who remained on the original randomized treatment, there were no significant differences between the four groups in any of the measured variables. Mean total cholesterol was highest in the group receiving Aza and MP (6.8 mmol/l) and lowest in the group receiving triple therapy (5.8 mmol/l; NS). Mean triglyceride level was highest in the group receiving Aza and MP (2.3 mmol/1) versus 1.8–2.2 mmol/l in the groups receiving triple therapy, Aza + CyA, and CyA + MP. For all patients mean triglyceride level was highest in the group receiving Aza and MP (2.7 mmol/1) and lowest in the group receiving triple therapy (1.7 mmol/l; P<0.05). Mean HDL cholesterol ranged from 1.5 to 1.6 mmol/l in all groups. Neither CyA concentration nor CyA or MP dose correlated with cholesterol or triglyceride concentration. However, the average MP dose was twice as high in the group receiving Aza and MP as in the other two groups employing steroids. Serum cholesterol and triglyceride concentrations were related to body mass index (r= 0.28, P= 0.045 and r= 0.30, P= 0.029, respectively). Hyperlipidemia was most common in the group receiving Aza and MP, The frequency of hypercholesterolemia (serum cholesterol level > 6.5 mmol/1) was 18%, 45%, 60%, and 35% for the patients continuing with the originally randomized treatment in the groups receiving triple therapy, Aza + CyA, Aza + MP, and CyA + MP, respectively. In a normal Finnish reference population, 35% of all males and 31% of allfemaleshaveaserumcholesterollevel above 6.5 mmol/l. Thus, only patients receiving Aza and MP had a clearly higher frequency of hypercholesterolemia than that found in a normal population. Taken together, this study shows no lipid abnormalities associated with the use of low-dose CyA for 2 years after transplantation. Hyperlipidemia occurring after transplantation is probably multifactorial and more associated with other risk factors than with the immunosuppressive therapy.     

Sirolimus improves the two-year outcome of renal allografts in African-American patients

The present study evaluated whether the addition of sirolimus to a cyclosporine (CyA)/prednisone (Pred) regimen mitigated the greater proclivity to acute rejection episodes and graft loss characteristic of African-American renal transplant recipients. Using Kaplan-Meier and log-rank tests, African-American renal transplant recipients treated with either CyA/Pred (n = 90) or sirolimus/CyA/Pred (n = 47) were compared with 120 Caucasian patients treated with sirolimus/CyA/Pred for 2-year rates of patient and graft survival as well as acute rejection episodes. Mean laboratory values were compared using analysis of variance and F-tests. Addition of sirolimus to the CyA/Pred regimen reduced the incidence of acute rejection episodes in African-Americans from 43.3 % to 19.2 % (P = 0.004), a value similar to Caucasian patients. The 97.9 % 2-year graft survival rate among 47 African-American patients treated with sirolimus/CyA/Pred was significantly higher than the 85.6 % rate shown among the 90 CyA/Pred-treated African-American transplant recipients (P = 0.0479) and similar to that in Caucasians. The 95.7 % patient survival rate among the African-American sirolimus/CyA/Pred group was similar to the 97.8 % rate in the African-American CyA/Pred cohort. Interestingly, there was no evident toxicity from the addition of sirolimus. The addition of sirolimus to a CyA-based regimen reduced acute rejection episodes and graft loss experienced by African-American renal transplant recipients. Received: 15 February 2000 Revised: 5 October 2000 Accepted: 3 April 2001     

Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine: A single center, five-year follow-up study

Abstract. In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time post-transplantation than Aza/P-treated patients ( P < 0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 μmol/l per year for Aza/P-treated patients and 2.4 μmol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m²/year in the Aza/P group and 1.07 ml/min per 1.73 m²/year in the CyA/P group ( P = 0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used. Thus, these data do not indicate a progression with time of the nephrotoxicity observed in CyA-treated patients.     

Renal handling of uric acid under cyclosporin A treatment

The renal handling of uric acid during cyclosporin A (CyA) treatment was investigated by clearance studies using 24-h urine collections in 28 paediatric renal transplant recipients (CyA group), and the results were compared with those of 19 renal transplanted children treated with azathioprine and prednisolone (AZA group), 35 children with chronic renal failure (CRF) and 10 children with normal renal function (N group). Serum uric acid levels were significantly higher in the CyA group (567±156 mol/l) compared with the AZA group (378±98), the CRF group (415±119) and the N group (290±68). Mean uric acid clearances in each group measured 3.9±2.8 ml/min per 1.73 m² (CyA), 5.6±3.4 (AZA), 4.0±2.2 (CRF) and 8.4±3.7 (N). Calculation of the net tubular uric acid reabsorption per millilitre glomerular filtration rate revealed a significantly increased value of 0.53±0.15 mol/ml in the CyA group (P<0.01) compared with 0.34±0.08, 0.29±0.15 and 0.27±0.07 mol/l for the AZA, CRF and N groups respectively. We therefore conclude that CyA treatment is associated with an increased net tubular reabsorption of uric acid, which may lead to hyperuricaemia.     

The in vivo effect of a new,in vitro,extremely potent vitamin D3 analog KH1060 on the suppression of renal allograft rejection in the rat

KH1060 is a new 20-epi-vitamin D₃ analog, which has exerted a considerable immunosuppressive potency in vitro. We have tested in vivo the effect of KH1060 on the suppression of renal allograft rejection in the rat. Allogenic kidney transplantation from DA donor rats to Lewis recipient rats treated intraperitoneally with KH1060 in doses from 0.2 to 6 g/kg/day, or saline (placebo group), or CyA 10 mg/kg/day for 10 days (positive control group), was performed. Median graft survival time in KH1060-treated groups was 7–9 days, in the placebo group 6 days, whereas CyA led to long-term graft survival, 34 days in 50% of rats and >100 days in 50% of rats. In vivo, KH1060 failed to prolong renal allograft survival considerably, and led to development of hypercalcemia. Our results stress the existence of a large discrepancy between the in vitro and in vivo immunoregulatory effects of this vitamin D analog.     

A prospective randomised study of the effect of nicardipine on ischaemic renal injury in renal allografts

In a prospective doubleblind trial, 127 kidneys were randomised to receive Eurocollins (n=65) or Eurocollins plus nicardipine (n=62) as a second flush solution at the time of organ retrieval. Delayed graft function occurred in 18 of 65 control kidneys (28%) and in 20 of 62 nicardipine kidneys (32%; P=0.7, Fischer's exact test). The mean (SD) serum creatinine at 6 weeks was 197 (138) mol/l in the Eurocollins group and 195 (159) mol/l in the nicardipine group (P=0.95). Eighteen recipients (28%) in the controlled Eurocollins group experienced a rejection episode in the first 6 weeks post-transplant compared to 17 (27%) in the nicardipine group (² with Yates' correction=0.027; P0.95). In this study, the addition of nicardipine to the kidney perfusion fluid did not have a beneficial effect on kidney function following transplantation.     

Renal allograft immunosuppression: II. A randomized trial of withdrawal of one drug in triple drug immunosuppression

Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal.     

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62±0.35 vs 1.62±0.23 mmol/l (P<0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44±0.32 vs 5.84±0.25 (P<0.02). CsA/P patients had higher serum levels of LDL-C (4.79±0.20 vs 3.43±0.19 mmol/l P<0.001) and apolipoprotein B concentrations (191±13 vs 128±9 mg/dl; P<0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73±0.13 vs 1.52±0.09 mmol/l; NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.     

Long‐term outcome of belatacept therapy in de novo kidney transplant recipients – a case‐match analysis

While belatacept has shown favorable short‐ and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long‐term outcome. Therefore, we performed a retrospective case‐match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)‐treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept‐treated patients compared with the CyA control group. Moreover, none of the belatacept‐treated patients had donor‐specific antibodies ≥10 years post‐transplantation compared with 38.5% of tested CyA‐treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single‐center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years post‐transplant which was comparable to that of similarly selected CNI‐treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long‐term graft survival with belatacept.     

儿童肾移植的临床研究

目的 总结儿童肾移植的临床经验.方法 回顾性分析1980年6月至2008年12月41例儿童肾移植的临床资料,其中1980-1993年(G1)有8例患儿,均未进行免疫诱导,术后采用以环孢素A+硫唑嘌呤+泼尼松为基础的免疫抑制方案;1994-2001年(G2)有18例患儿,均应用抗淋巴细胞球蛋白免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯(或硫唑嘌呤)+泼尼松的方案;2002年后(G3)有15例患儿,均应用抗白细胞介素-2受体单克隆抗体(IL-2RA)免疫诱导,术后采用他克莫司(或环孢素A)+吗替麦考酚酯+小剂量泼尼松(或无泼尼松)的方案.分别对三个阶段患儿术后急性排斥反应(AR)和移植肾功能恢复延迟(DGF)等并发症发生率、存活率及生长发育情况等进行比较.结果 41例患儿术后1、3、5年人/肾存活率分别为97.6%/90.2%、95.1%/82.9%和90.2%/75.6%,其中G1为87.5%/75.0%、75.0%/50.0 %和75.0%/50.0%、G2为100.0%/94.4 %、100.0%/83.3%和94.4%/72.2%以及G3为100.0%/100.0%、100.0%/100.0%和100.0%/93.3%,G3明显高于G1(P<0.05),但与G2无明显差异.41例中共有13例发生AR,发生率为31.7%,其中G3的AR发生率分别为13.3%,明显低于G1和G2的50.0%和38.9%(P<0.01).G1、G2和G3患儿的身高分别增长了(2.9±0.6)、(3.2±0.6)和(3.8±0.9)cm,G3患儿身高的增长幅度最为明显(P<0.05).G1、G2和G3患儿间DGF发生率无明显差异,高血压和感染是最为多见的并发症.结论 良好的组织配型、适宜的手术方法、恰当的免疫抑制剂血药浓度及AR早期诊断是保证儿童肾移植成功的关键.IL-2RA免疫诱导能够有效地降低AR发生率,而小剂量激素或无激素方案最大程度的改善了影响患儿骨骼发育的限制因素,促进患儿生长.     

Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile

The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti-hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69±0.20, post 0.84±0.23, P<0.05), lower serum cholesterol levels (pre 6.8±1.0, post 5.8±1.2, P<0.05), lower mean arterial pressure (pre 111±14, post 102±8, P<0.05) and a lower hypertension index (pre 2.45±2.77, curr 1.62±1.70, P<0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly.     

肾移植后免疫抑制用药方案与移植肾长期存活的关系

目的 分析肾移植后不同的免疫抑制用药方案对移植肾长期存活的影响。方法 根据不同用药组合将患者分为环孢素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）和泼尼松（Ｐｒｅｄ）三联治疗组、ＣｓＡ和Ｐｒｅｄ二联治疗组、Ａｚａ和Ｐｒｅｄ传统二联治疗组。统计分析免疫抑制用药、排斥反应发生及人、肾存活情况;对发生排斥反应的患者追踪其发生排斥前１２个月内的药物更动情况。结果 采用三联治疗的患者人／肾５年存活率（８８％／７８％）显     

Microcirculatory disturbances and leucocyte adherence in transplanted livers after cold storage in Euro-Collins,UW and HTK solutions

Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 mol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3±0.2 m; mean±SEM) compared with the UW group (9.5±0.2 m; P<0.05) and HTK group (10.2±0.8 m; P<0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5±1%), while this phenomenon was less pronounced in the UW group (14.5+1.1%; P<0.05) and HTK group (16.3±0.7%; P<0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7+1.3%) compared with the UW group (30.5+2.1%) and the HTK group (34.4+0.8%). Microcirculatory failure and cell swelling in the EC group might be due to the lack of osmotic substances or oxygen radical scavengers included in UW (allopurinol, glutathione) and HTK (mannitol) solutions. In conclusion, cold storage of livers in UW and HTK solutions results in better preservation of the microcirculation and prevention of adhesion of leucocytes after transplantation compared with the EC solution.     

免疫抑制方案对移植肾早期各种功能状态的治疗影响

目的：分析肾移植术后早期 不同的肾功能状态下，三种免疫抑制用药方案对移植效果的影响。方法：将1196例肾移植患者根据其初始的免疫抑制用药方案分为A、B、C三组。A组：环孢素A（CsA) 硫唑嘌呤(Aza) 泥尼松（Pred);B组：CsA 霉酚酸酯（MMF）＋Pred;C组：他克莫司（FK506）＋MMF（或Aza) Pred。根据移植后早期肾功能状态，将患者分成肾功能即刻恢复正常（IGF）、缓慢恢复正常（SGF）、未恢复正常（AGF）和延迟恢复正常（DGF）四种情况。统计四种肾功能状态下，A、B、C三组患者的1年移植肾存活率、急性排斥发生率及治疗逆转率、药物副作用和相关并发症。结果：在四种不同肾功能状态下，B组或C组患者的移植肾1年存活率高于A组；B组和C组的急性排斥发生率均低于A组，急性排斥反应逆转率高于A组，但差异无显著性；B组或C组的肝功能损害、肾毒性、高血压的发生率明显低于A组。结论：在肾移植后各种肾功能状态下，B组和C组的免疫抑制方案，都可减少急性排斥反应、药物毒副作用及相关并发症的发生率，提高移植肾的存活率。     

Paediatric cadaveric renal transplantation

Since June 1985 ten consecutive paediatric cadaveric renal transplant recipients (aged from 7 to 15 years) have been studied prospectively to evaluate a triple immunosuppressive regime of low-dose cyclosporin A (CyA), azathioprine (AZA) and prednisolone (PNL) with the aim of eliminating PNL from the regime within 6 months. Follow-up has been over 6–18 months. Patient and graft survival are both 100%. Median (range) serum creatinine values at 6 months were 0.09 (0.05–0.14) mmol/l (n=10) and 0.09 (0.06–0.16) mmol/l (n=5) at 12 months. Readily reversible acute rejection episodes occurred in five patients (50%); two of these episodes occurred soon after cessation of PNL. Six months post-transplantation, PNL had been discontinued in six patients (60%). After 12 months, three of five patients were still not receiving PNL. Complications included hypertension (seven patients), cytomegaloviral infections (three patients), labial herpes simplex (one patient), leucopenia (two patients), marked hirsuitism (four patients) and transient CyA nephrotoxicity (one patient). Following transplantation, all children had growth velocities greater than 5 cm/year and seven have growth patterns which suggest that catch-up growth may be occurring. This preliminary study shows that a triple immunosuppressive regime of low-dose CyA, AZA and PNL allows excellent patient survival, graft survival and graft function and has been associated with few complications, including a low incidence of CyA nephrotoxicity. Growth rates are very encouraging and in a high proportion of children it has been possible to discontinue PNL completely.     

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients — a randomised prospective study

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P=0.0223) and 4-year (P=0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P<0.01). Group B also experienced fewer rejection episodes than groups A and C (P<0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.