Transplantation of pediatric cadaveric kidneys into adult or pediatric recipients

In Japan, nationwide cadaveric organ sharing for kidney transplantation by the Japan Organ Transplant Network (JOTN) has operated since April 1995. This study retrospectively analyzed the long-term results of single pediatric donor kidneys transplanted into adult or pediatric recipients at a single center. From March 1983 to December 2002, 281 cadaveric renal allografts were transplanted at our center, including, 17 recipients of cadaveric kidneys from donors aged less than 16 years. We divided these 17 recipients into two groups: 10 adult recipients (group 1; G1) and seven pediatric recipients (group 2; G2). HLA-AB, -DR mismatches were 1.3 +/- 1.3, 0.7 +/- 0.5 in G1 and 2.6 +/- 1.3, 1.4 +/- 0.8 in G2, respectively (P < .05 for both). The end of the observation of this study was March 2003. Among G1, two recipients died with functioning grafts and one died after graft loss. Among G2, no recipients died. Patient survival rates at 1 and 5 years were 90% and 80% in G1 and 100% and 100% in G2, respectively. At the end of the observation in this study, five recipients among G1 and six recipients among G2 had functioning grafts. Graft survival rates at 1 and 5 years were 90% and 80% in G1 and 85.7% and 85.7% in G2, respectively. Our results demonstrate that transplantation of pediatric cadaveric kidneys into pediatric recipients was excellent compared to adult recipients in terms of survival. Priority to pediatric patients should be given especially in cases of pediatric donors.     

Transplantation of kidneys from pediatric cadaver donors to adult recipients

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.     

Hyperlipidemia in pediatric kidney transplant recipients treated with cyclosporine

Hyperlipidemia is a risk factor for cardiovascular disease in adult kidney transplant (Tx) recipients. We sought to determine the prevalence of, and the risk factors associated with, hyperlipidemia in pediatric kidney Tx recipients on cyclosporine (CsA). We identified 59 patients (mean age 8.2+/-5.7 years) transplanted between 1 January 1991 and 31 December 1993. Pre Tx, 34% had elevated total cholesterol [TC >200 mg/dl (5.17 mmol/l)]; 54% had elevated triglycerides [TG >200 mg/dl (2.26 mmol/L)]. Mean TG was higher pre Tx in dialysis (versus nondialysis) patients: 306 mg/dl (3.46 mmol/l) versus 228 mg/dl (2.58 mmol/l) ( P=0.04). Mean TC was higher in peritoneal dialysis than hemodialysis patients: 222 mg/dl (5.74 mmol/l) versus 169 mg/dl (4.37 mmol/l) ( P=0.03). Pre Tx and 3-year values correlated (TC, r=0.49, P=0.0008; TG, r=0.41, P=0.001); 3- and 5-year TC values correlated ( r=0.57, P=0.003). At 5 years post Tx, 41% of the recipients had elevated TC; 14% had elevated TG. Recipients with elevated TC had higher mean CsA concentrations at 1 year post Tx ( P=0.03). Recipients with elevated TG tended to receive more prednisone ( P=0.06). At 5 years post Tx, recipients had a high prevalence of hyperlipidemia. The identification and treatment of hyperlipidemia should be included in pediatric kidney Tx protocols.     

Effect of cyclosporine A on long-term allograft function in pediatric renal transplant recipients

There have been concerns regarding long-term adverse effects of cyclosporine A (CSA) on renal allograft function. In a retrospective study, we compared long-term allograft function up to 70 months after renal transplantation in pediatric recipients treated with and without CSA, using iothalamate clearance to assess glomerular filtration rate. Patients received CSA, prednisone, and azathioprine (CSA group,n=16) or prednisone and azathioprine alone (Pred/AZA,n=11). At 48 months post transplant, the iothalamate clearances (mean±SD) were 57.9±26.8 ml/min per 1.73 m² in the CSA group and 68.5±20.2 in the Pred/AZA group (P>0.05). The mean of the slopes of individual iothalamate clearances versus time during the first 70 months following transplantation were –0.156 in the CSA group and –0.095 in the Pred/AZA group. Neither slope was statistically different from zero. These data suggest that allograft function is not significantly depressed by CSA at 48 months post transplantation and that there is no greater rate of decline in allograft function up to 70 months post transplantation in patients receiving CSA when compared with the AZA/Pred group.     

Evaluation of pediatric cadaver kidneys transplanted into adult recipients receiving cyclosporine

The major problem in clinical transplantation is the imbalance between the need for cadaveric organs and the available numbers of donors. If pediatric kidneys were transplanted into adult recipients when no pediatric recipient was available, the potential number of renal donors would be increased by 15 to 20%. Some centers are reluctant to use pediatric kidneys for adult recipients because of recent reports indicating poorer patient and allograft survival, increased delayed graft function, increased post-transplant hypertension and increased technical complication. (There also has been concern that the nephrotoxic effect of cyclosporine A would retard the organ growth that is necessary to provide normal renal function in adults.) A retrospective analysis was performed on 18 adult recipients who received kidneys from cadaver donors 14 months to 12 years old (group 1). These patients were compared to 106 adult recipients who received kidneys from donors greater than 12 years old (group 2). Actuarial patient survival at 1 year was 85% for group 1 and 95.8% for group 2 (p equals 0.13), while 1-year actuarial allograft survival was 83.1% for group 1 and 81.1% for group 2 (p equals 0.87). There was no significant difference between groups 1 and 2 in the frequency of delayed graft function, serum creatinine at 1, 3 and 6 months after transplantation, incidence of post-transplant hypertension or frequency of surgical complications. It is of interest that the pediatric kidneys had significant growth during the initial post-transplant month. Sonographic examination at postoperative days 1 and 30 demonstrated a mean increase in size from 80.7 to 143.5 cm. (p less than 0.001). In this series pediatric kidneys were safe and effective donor organs in adult recipients, and increased the available number of organs by 15%.     

The advantage of allocating kidneys from old cadaveric donors to old recipients: a single-center experience

BACKGROUND: In January 1999 a new kidney allocation program was launched by the Eurotransplant Foundation, the 'Eurotransplant Senior Program' (ESP). Cadaveric donors above the age of 65 yr are allocated to kidney transplant recipients of the same age group. METHODS: Using a single-center database, 91 patients who underwent first renal transplantation at the age of 65 yr and older in the years 1999-2002 were identified. Fifty-six patients were transplanted through ESP allocation (study group) and 35 patients (control group) via normal Eurotransplant Kidney Allocation System (ETKAS) procedure. RESULTS: Age, sex and comorbid conditions did not differ by group. The rate of acute rejection episodes, primary non-function, delayed graft function, perioperative mortality did not differ by group. Serum creatinine was significantly lower in the ETKAS group (1.3 vs. 1.9 mg/dL; p=0.015) from six months after the transplantation on. Overall graft survival at six yr was 56% in the ETKAS group and 52% in the ESP group. With 73% in the ETKAS group and 71% in the ESP group, cumulative patient survival according to the Kaplan-Meier estimation was not statistically different at five yr. CONCLUSIONS: We did not find a relevant difference in the outcome between young and old kidney transplants in old recipients after this long observation period.     

Long-term follow-up of kidneys transplanted from elderly cadaveric donors

Summary This report examines the long-term results obtained in 50 patients transplanted between 1977 and 1990 with kidneys from cadaveric donors aged 55–70 (median 59) years. The recipients comprised 27 men and 23 women aged 8–68 (median 42) years. In all, 20 patients (40%) had end-stage renal disease on the basis of glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine and prednisone in all patients in addition to cyclosporine in the 35 patients transplanted since 1985. Immediate graft function occurred in 18 patients (36%), and 36 patients (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%) had functioning grafts at 5 years posttransplant, and at up to 13 years of follow-up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12 patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3 years), and 5 of these patients died with functioning grafts. These 5 deceased recipients and the 22 who remain alive with functioning grafts had a mean antigen match of 2.27 with their donors. The other 23 patients whose grafts failed had a mean antigen match of 2.13 (P=0.77). The 15 recipients who were transplanted prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of 67% and 47%, respectively, as compared with their counterparts, who took cyclosporine-based immunosuppression (74% and 51%, P=0.58 and 0.76, respectively). Likewise, the 32 recipients with delayed graft function had lower 1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared with the group with immediate graft function (83% and 56%, P=0.18 and 0.56, respectively). We conclude that acceptable long-term patient and graft survival may be achieved by transplanting these organs and that the degree of HLA matching does not affect their outcome significantly. Patients with immediate allograft function also tended to do better over the long term. Although cyclosporine-based immunosuppression was advantageous within 1 year of transplant, its beneficial effect was less marked 5 years out.     

Transplantation of adult recipients by single cadaveric kidneys from pediatric donors weighing < or = 25 kg can be a reliable option.

The evidence in favor of transplanting single allografts from cadaveric pediatric donors into adult recipients is equivocal. This study was performed to assess the outcome of transplantation of single kidneys from pediatric donors weighing < 25 kg. Thirty-five adults transplanted by renal allografts from pediatric donors weighing < 25 kg were compared with 30 matched recipients of kidneys from adult donors. Donors in study group were aged 4.2 +/- 2.1 years weighing 16.0 +/- 5.3 kg. In the study group, surgical complications occurred in five of 35 patients, in the control group four of 30. Serum creatinine reached nadir in 47.5 days in study group versus 30 days in controls (P < 0.01). Serum creatinine at 1 and 3 years were comparable in both groups. A 38.9% had proteinuria at 1 year in the study group compared with 22.7% in controls (P = 0.36). One-year graft survival was 91.7% in the study group versus 92.8% for controls. The surgical complications and graft survival in the study group was comparable with that of controls. The incidence of proteinuria may be more frequent, but does not appear to impact graft function. The use of single, as compared with paired, pediatric donor kidneys would allow more patients to be transplanted with equivalent results.     

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine

INTRODUCTION: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. METHODS: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. RESULTS: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001. CONCLUSIONS: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.     

Pharmacokinetics of cyclosporine in pediatric long-term liver transplant recipients converted from Sandimmun to Neoral

Absorption of cyclosporin from the microemulsion formulation Neoral is less variable than from Sandimmun. Because of a lack of data in pediatric liver transplant recipients, the pharmacokinetic profiles with Sandimmun and Neoral were compared in a conversion study. Thirty-eight children with stable graft function were converted 2–12.3 years post-transplant at a 1:1 ratio. The trough-level (C_min) with Neoral was 123 ± 39 ng/ml versus 134 ± 29 ng/ml with Sandimmun (P = NS), the area under the time-concentration curve (AUC) was 3325 ± 1125 ng_*h/ml versus 2423 ± 846 ng_*h/ml (P < 0.001), the peak concentration (C_max) was 650 ± 280 ng/ml versus 337 ± 142 ng/ml (P < 0.001), and the median time to C_max was 2 h (range 0.5–3 h) versus 4 h (range 1–8 h; P < 0.05). The weak correlation between C_min and AUC with Sandimmun (r = 0.5; P = NS) was improved by using Neoral (r = 0.7; P < 0.001). The best predictor of AUC was the 2-h concentration (C_{2 h}) of Neoral (r = 0.9; P < 0.001). Increased absorption and a more predictable pharmacokinetic profile with Neoral permit safer therapeutic monitoring in children. The exclusive measurement of Neoral-C_{2 h} allows one to estimate drug exposure with high precision ( > 90 %). Received: 12 February 1997 Received after revision: 16 May 1997 Accepted: 5 June 1997     

婴儿供肾儿童肾移植四例临床分析

目的 探讨婴儿供肾儿童肾移植的临床效果.方法 回顾性分析4例婴儿供肾儿童肾移植的临床资料、手术方式、免疫抑制剂应用和随访情况.结果 术后随访2～14个月,所有受者均存活.1例术后发生肾功能延迟恢复,经腹膜透析治疗后恢复;1例出现尿漏,经再次手术后恢复;1例因移植肾动、静脉血栓形成而切除移植肾.3例受者移植肾功能恢复良好,末次随访时血肌酐分别为70 μumol/L、102 μmol/L和83 μmol/L.结论 婴儿供肾儿童肾移植短期效果尚可,有利于缓解供肾短缺情况,值得深入研究.     

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Though mycophenolate mofetil has markedly reduced the incidence of acute rejection in renal transplantation, a significant improvement in graft survival has been more difficult to demonstrate. This retrospective study compares an historical control group of 210 consecutive renal transplant patients, who had received ATG induction associated with cyclosporin, prednisolone and azathioprine, with 187 patients receiving mycophenolate instead of azathioprine. The incidence of acute rejection was decreased with mycophenolate. In rejection-free patients, the 3-year graft survival rates were equivalent. In contrast, graft survival at 3 years improved significantly for patients who experienced a rejection crisis and remained under the initial triple drug regimen with mycophenolate compared to the patients of the historical group who were kept on azathioprine after a rejection episode. In conclusion, mycophenolate mofetil is not only able to reduce the incidence of acute rejection but could also improve the prognostic significance of acute rejection crises.     

Effective long-term immunosuppression maintained by low cyclosporine levels in primary cadaveric renal transplant recipients

Nephrotoxicity and cost are the major problems in the use of cyclosporine (CsA) in renal transplantation. Thus, maintenance of CsA levels at the lower limits of the therapeutic range is desirable. The lowest CsA level effective in preventing rejection while avoiding nephrotoxicity has not been defined. We report on 44 primary cadaveric renal transplant recipients treated with a protocol that involved a progressive reduction in the trough CsA levels. CsA was initiated at an oral dose of 15 mg/kg, and this dose was adjusted to achieve serum trough levels, as measured by radioimmunoassay, of 150-200 ng/ml during the first month, 100-150 ng/ml during the second month, 75-100 ng/ml during the third month, and 50-75 ng/ml thereafter. Patient and graft survival at 18 months were 94% and 83.6%, respectively. The mean daily CsA doses were 6.7 +/- 3.1 mg/kg at 6 months, 5.5 +/- 3.2 mg/kg at 12 months, and 4.7 +/- 2.4 mg/kg at 18 months. Corresponding trough serum CsA levels were 94 +/- 59 ng/ml, 64 +/- 22 ng/ml, and 44 +/- 21 ng/ml at 6, 12, and 18 months, respectively. Mean serum creatinine concentrations were 1.8 +/- 0.6 mg/dl at 6 months, 1.7 +/- 0.5 mg/dl at 12 months, and 1.6 +/- 0.5 mg/dl at 18 months. The mean serum creatinine concentration at 18 months was not significantly different from that of 18 conventionally treated primary cadaveric renal transplant recipients (1.6 +/- 0.5 vs. 1.4 +/- 0.4 mg/dl, P = .31). A total of 67% of patients did not have any rejection episodes under this protocol, while 71% of patients never developed CsA nephrotoxicity. No patient was taken off CsA for progressive nephrotoxicity. We conclude that trough serum CsA levels of 50-75 ng/ml, as measured by radioimmunoassay, are sufficient to maintain effective immunosuppression in the long-term management of primary cadaveric renal transplant recipients. These values are much lower than previously recommended, and this approach ameliorates chronic CsA nephrotoxicity.