Kidney Transplantation In Children Research Articles

A systems-based approach to managing blood pressure in children following kidney transplantation.

Hypertension is one of the most common and well-known complications following kidney transplantation in children. Yet, despite numerous available therapies many pediatric kidney transplant recipients continue to have poorly controlled blood pressure, suggesting that traditional approaches to blood pressure management in this population might be inadequate. Over the last two decades, the Chronic Care Model has been developed to improve chronic illness outcomes through delivery system design and clinical information systems that support patient self-management and provider decision-making. In this educational review we discuss key elements of managing blood pressure following pediatric kidney transplantation and suggest ways that they may be reliably implemented into clinical practice using principles from the Chronic Care Model.

Review of combined liver and kidney transplantation in children.

In this review, we focused on CLKT with regard to indication, results, outcome, and future developments. PH1 is one of the most common diagnoses for adult and pediatric patients qualifying for CLKT. The other major indication for combined transplantation is ARPKD. CLKT appears to be superior to sequential liver and kidney transplantation in the majority of patients and overall results following CLKT are now good, even in small children. Clinical observations suggest that there is an immunological advantage of CLKT in comparison with isolated liver or kidney transplantation. More clinical studies are necessary to identify the best candidates for CLKT while the availability of donor organs is low.

De novo development of antibodies to kidney‐associated self‐antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children

Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation--a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.

G473 Outcomes of abo incompatible kidney transplantation in children

Objective ABO blood group incompatible transplantation (ABOi) has become increasingly common over the last decade, in part due to a shortage of suitable deceased donor allografts. Whilst encouraging data is emerging on short and medium term graft outcomes in adults, ABOi in children is rare; pre-transplant conditioning in paediatric patients remains challenging and concerns persist about an increased risk of rejection. Encouraged by good results in a large number of adult ABOi transplants, we extended our programme to paediatric recipients, and here report the largest European cohort. Methods A retrospective analysis of all ABOi paediatric renal transplant recipients in the 2 largest centres in the UK sharing the same tailored desensitisation protocol. Patients with pre-transplant titres 1 in 8 or above received rituximab one month prior to transplant; tacrolimus and mycophenolate mofetil were started one week pre-op. Antibody removal was performed to reduce titres to 1 in 8 or less at surgery. No routine post-op removal was performed. Results Ten children (age 2–14 years) underwent an ABOi kidney transplant (Figures 1 and 2 and Table 1). Graft and patient survival was 100%. Baseline titres, tailored desensitisation and graft outcomes are shown in table. One patient developed grade IIa rejection after 2 weeks successfully treated with anti-thymocyte globulin;no histological evidence of rejection in other 9 patients. Another patient had a rise in titre of 2 dilutions at week one treated with 2 immunoadsorption sessions. Nine patients had good graft function (eGFR 30–130 mls/min/1.73m2) at last follow up (range 1–36 months); one patient had eGFR 22 ml/min/1.73m2. One patient developed CMV and BK; another EBV and BK. Conclusion ABOi transplantation in children appears to have an optimal outcome with good graft survival, low risk of rejection and infectious complications.

Advances in Pediatric Renal Transplantation

The science of kidney transplantation in children has advanced remarkably in the last 40 years [1, 2]. As kidney transplants in adult recipients were becoming more common with improving shortand long-term outcomes, results in children were lagging behind. This lag was attributed to multiple factors: greater surgical and technical problems in small children, different metabolism for needed drugs, lack of actionable scientific data, and studies with inadequate sample sizes to make definitive research conclusions, among others.

Outcomes of Combined Liver–Kidney Transplantation in Children: Analysis of the Scientific Registry of Transplant Recipients

Combined liver–kidney transplantation (CLKT) in children is uncommon and outcomes have not been well defined. Using the Scientific Registry of Transplant Recipients, data were analyzed on 152 primary pediatric CLKTs performed from October 1987 to February 2011, to determine their outcome in the largest series reported to date. Patient survival was 86.8%, 82.1% and 78.9% at 1, 5 and 10 years, liver graft survival was 81.9%, 76.5% and 72.6%, and kidney graft survival was 83.4%, 76.5% and 66.8%. By way of comparison, the Registry was queried for pediatric patient survival following isolated liver transplantation (LT) during the same time frame: 86.7%, 81.2% and 77.4% and following isolated kidney transplant (KT): 98.2%, 95.4% and 90% at 1, 5 and 10 years. In patients having undergone CLKT, primary hyperoxaluria was associated with reduced patient (p = 0.01), liver graft (p = 0.01) and kidney graft survival (p = 0.01). Furthermore, graft outcome following CLKT improved over the past decade (p = 0.04 for liver, p = 0.02 for kidney), but this did not translate into improved patient outcome (p = 0.2). All in all, our results confirmed that survival following LT was less than following KT, and that CLKT offered similar patient survival to isolated LT.

Recent developments in kidney transplantation in children.

Renal transplantation in childhood is a well established procedure with excellent short-term outcomes. However, waiting times for transplantation are still relatively long if living donation cannot be performed, and long-term outcomes after transplantation have not significantly improved during the last decade. This review describes alternative modalities to improve donation rates such as en bloc kidney transplantation from young donors, ABO-incompatible transplantation and kidney paired donation. This review also deals with long-term post-transplant morbidities, such as follows: first, medication side-effects (metabolic syndrome, cardiovascular disease) and with the benefits of steroid and calcineurin inhibitor drug minimization; second, the deleterious impact of viral infections and their management and third, chronic antibody-mediated rejection, its therapeutic and prevention possibilities. Donor shortage and long-term morbidities, after transplantation, are still relevant issues in paediatric renal transplantation medicine. Significant research and efforts have been made to advance the field and create novel approaches for improvement of transplantation rates and post-transplant graft or patient survival. These modalities are to be established in the routine setting.

Predictive Factors of Graft-Censored Failure in Pediatric Kidney Transplantation

Kidney transplantation in children has shown steady improvement in graft survival outcome over the last decades. Using data obtained from the transplantation registry of our center between 1984 and 2012, we assessed the independent determinants of graft failure using the Cox proportional hazards regression. Altogether, 128 recipients younger than 18 years of age at the time of kidney transplantation and who had >3 months graft survival were studied. During 9.95 years of medium follow-up, 27 censored graft failures occurred. Censored graft survival rates at 5, 10, 15, and 20 years post-transplantation were 93%, 82%, 70%, and 63%, respectively. Studied factors included recipient and donor age, recipient gender, dialysis vintage, donor/recipient cytomegalovirus (CMV) serology, panel-reactive antibody percentage, human leukocyte antigen mismatching, previous transplantation number, donor type (deceased vs living donation), cold ischemia time, induction therapy with antithymocyte globulin, occurrence of acute tubular necrosis, and development of acute rejection. Using univariate analysis, the significant predictors for graft-censored failure were adult donor (P < .001), recipient age (P = .035), human leukocyte antigen mismatching (P = .025), antithymocyte globulin induction (P = .03), and development of acute rejection (P < .001). Two factors independently predicted graft-censored failure in multivariate analysis. The odds ratios for graft failure in patients with acute rejection and in children who received an organ of an adult were 3.744 and 4.962, respectively. Pediatric recipients should receive the first priority for allografts from pediatric donors and acute rejection should be meticulously prevented.

Outcome of Kidney Transplantation in Children With WT1 Gene-Related Disease (Drash, Frasier Syndrome).

Background: The WT1 gene mutations observed in patients with Denys-Drash (DDS) and Fraisure syndrome (FS) are associated with genitourinary development and tumorigenesis. Kidney transplantation (KT) is recommended for children who progress to real failure. However, limited information is available regarding the long-term outcome and the management of intersex disorders after KT. Methods: Retrospective study of 20 pediatric patients with WT1 gene-related disorders (DDS; 14 and FS; 6) who have undergone KT between 1990 and 2013 was conducted. Results: Fourteen patients had a 46XY karyotype; 6 of these XY patients had female phenotype (1 in DDS and 5 in FS) and they have been raised as a girl with bilateral gonadectomy. 6 XY patients had ambiguous phenotype and had a series of surgical repair for hypospadias and undescended testis until 2 years of age. Five patients with a 46XX karyotype had female genitalia. WT1 gene analysis was performed in 18 patients, which showed heterozygous germline mutations in exon 9 (n=11), intron 9 (n=5), exon 7 (n=1), and exon 8 (n=1). Wilms' tumors occurred in 7 of 14 patients with DDS; 2 males and 5 females, and the median age at diagnosis was 1.3 years. In addition, 2 of 6 patients with FS developed gonadoblastoma. The mean waiting time for KT after completion of chemotherapy for Wilms' tumor was 4.1 years. All recipients underwent bilateral nephrectomies before KT. The mean age at dialysis was 3.2±3.8 years in 14 patients with DDS and 8.7±5.0 years in 6 patients with FS. The mean age at KT was 5.6±3.3 years in patients with DDS and 11.8±6.8 years in patients with FS. Acute rejection rate was compatible with control group of patients with WT1nonrelated disease. One patient had chemotherapy because of recurrent Wilms' tumor 4.6 years after kidney transplantation. However, graft survival at 1-, 5-, and 10 year posttransplant was 100%, 100%, and 80%, respectively. Fine catch-up growth was observed except for 3 children who received heavy chemotherapy for the treatment of Wilms' tumor. Six 46XY female patients have received hormonal supplement from puberty. Conclusions:Abnormal sexual differentiation has been observed in all XY patients with WT1 mutation. The outcome of children with DDS of FS who proceeded to KT is compatible with children with other diagnosis

New-onset diabetes after kidney transplant in children.

The development of new-onset diabetes after kidney transplantation (NODAT) is associated with reduced graft function, increased cardiovascular morbidity and lower patient survival among adult recipients. In the pediatric population, however, the few studies examining NODAT have yielded inconsistent results. Therefore, the true incidence of NODAT in the pediatric population has been difficult to establish. The identification of children and adolescents at risk for NODAT requires appropriate screening questions and tests pre- and post-kidney transplant. Several risk factors have been implicated in the pathogenesis of NODAT and post-transplant glucose intolerance, including African American race, obesity, family history of diabetes and the type of immunosuppressant regimen. Moreover, uremia per se results in a state of insulin resistance that increases the risk of developing diabetes post-transplant. When an individual becomes glucose intolerant, early lifestyle modification and antihyperglycemic measures with tailoring of the immunosuppressant regimen should be implemented to prevent the development of NODAT. For the child or adolescent with NODAT, antihyperglycemic therapy should be prescribed in order to achieve optimal glycemic control, ultimately reducing complications and improving overall allograft and patient survival. In this article, we review the risk factors, screening methods, diagnosis, management and outcome of children and adolescents with NODAT and post-kidney transplant glucose intolerance.

USE OF TACROLIMUS IN CHILDREN FOR TRANSPLANTATION OF KIDNEYS TAKEN FROM LIVE RELATIVE DONORS

The authors present their experience of immunosuppressive therapy with calcineurin blockers in the post-transplantation period (after living-related kidney transplantation). The study was aimed at determining effect of immunosuppressive drug tacrolimus on results of living-related kidney transplantation in children (group 1). The 58 children, who did not receive tacrolimus in the process of the study, constituted the control group (group 2). The following parameters were used to perform comparative analysis: Kaplan-Meier cumulative survivability of recipients and transplants, Cox cumulative hazard level, log-rank test. Moreover, we calculated the rates of transplanted kidney loss and mortality. Results: survivability of transplants and patients was higher in the main group than in the control group (p < 0.05). Conclusions: thus, results of the performed analysis allow claiming that use of tacrolimus for immunosuppressive therapy positively affects results of the living-related kidney allotransplantation in children.

Infections Following Kidney Transplant in Children: A Single-Center Study

Introduction: Infections are a major cause of morbidity and mortality in pediatric patients undergoing kidney transplantation (KT). Aim and Methods: To determine the patterns of infectious complications during the first 6 months post transplantation, we report our single center experience with data from pediatric kidney recipients transplanted between 2006 and 2011. Results: Thirty-two children (20 males) were submitted to KT. The most common cause of end-stage renal disease (ESRD) was congenital anomalies of the kidney and urinary tract (CAKUT) accounting for 62%. Over the first 6 months post-transplant period, twenty-eight (87.5%) children developed a total of 77 infections, mainly urinary tract infections (UTI) (64.9%). CAKUT etiology of ESRD and UTI before KT increased the risk to develop more than one episode of UTI [71.4% vs. 14.3% and 81.8% vs. 18.2%, respectively; p < 0.05]. Twenty-three (29.9%) viral infections occurred. Cytomegalovirus (CMV) was the most common opportunistic pathogen, occurred in 11 patients and was more frequently in those with a donor (D)+/recipient (R)- CMV sero-status [74.5% vs. 25.5% (p < 0.05)]. A polyomaviruses (BKV) disease with nephropathy and meningitis was registered. The majority of infectious episodes had mild or moderate severity. No deaths occurred. Conclusion: A significant number of patients presented infectious complications during the first 6 months post transplantation. UTI are the most common type of infection, followed by viral infections, particularly CMV. Recognition, prevention and early treatment of infections are of major importance.

Solid tumors following kidney transplantation in children

Kidney transplant recipients have an increased risk of cancer. Data on non-LPD malignancies (solid tumors) in pediatric renal transplant recipients are limited. We performed a cohort study using the NAPRTCS transplant registry to describe the incidence of non-LPD malignancy compared with the general pediatric population. The observed incidence rate of non-LPD malignancy in the NAPRTCS transplant registry was 72.1 per 100,000 person-years (SIR 6.7; 95% CI, 5.3, 8.5); a 6.7-fold increased risk compared with the general pediatric population (10.7 cases per 100,000 person-years). Non-LPD malignancy was diagnosed in 35 subjects at a median of 726 days post-transplant. The most common type of malignancy was renal cell carcinoma. The increased risk of non-LPD malignancy was seen in all patients regardless of age, gender, race, etiology of end-stage kidney disease, and transplant era. The specific type of immunosuppression was not identified as a risk factor. In this first large-scale study of North American pediatric renal transplant recipients, we observed a 6.7-fold increased risk of non-LPD malignancy compared with the general pediatric population. Further examination of this unique patient population may provide greater insight into the impact of transplant and immunosuppression on malignancy risk.

Kidney transplantation in children weighing less than 15 kg: Extraperitoneal surgical access–experience with 62 cases

Small children are a challenging group in whom to perform KT. This retrospective study analyzed the results of 62 KTs in children weighing <15kg, performed between 1998 and 2010, using extraperitoneal access and anastomosis of the renal vessels of donors to the aorta and IVC or iliac vessels of the recipients. Thirty-two (51.6%) grafts were LRDTs and 30 (48.4%) were DDRTs-28 of them pediatric. The mean age at KT was 3.7±2.2yr (1-12), and the mean weight was 12.3±2.1kg (5.6-14.9). Ten children weighed <10kg, and five (8.1%) children presented previous thrombosis of the venous system. At one and fiveyr, patient survival was 93.2% and 84.2%, and graft survival was 85.2% and 72.7%. There were no differences between the rates for LRDT and DDRT. There were six vascular complications (four vascular thromboses, one laceration, and one renal artery stenosis) and two perirenal collections. Extraperitoneal access is a valid KT technique in children weighing <15kg.

Combined liver and kidney transplantation in children

Simultaneous combined liver-kidney transplantation (CLKT) is a rare operation in pediatric patients so that annually only 10-30 operations are performed worldwide. The main indications for CLKT are primary hyperoxaluria type 1 and autosomal recessive polycystic kidney disease. In addition, CLKT is indicated in individual patients with metabolic or cirrhotic liver diseases and end-stage kidney disease. The surgery and immediate post-operative management of CLKT remain challenging in infants and small children. The patients should be operated on before they become severely ill or develop major systemic manifestations of their metabolic disorder. The liver allograft is immunologically protective of the kidney graft in simultaneous CLKT, often resulting in well-preserved kidney function. The long-term outcome after CLKT is nowadays comparable to that of isolated liver and kidney transplantations.

Reliable Individualized Monitoring Improves Cholesterol Control in Kidney Transplant Recipients

To develop and evaluate a system for reliable and efficient individualized risk-based monitoring of cholesterol and 11 other tests after kidney transplantation in children. We identified system components that drive reliable individualized monitoring and used quality improvement methods to develop and implement interventions, including (1) monitoring schedules individualized by dyslipidemia risk assigned to each patient, (2) automated previsit decision support from our electronic medical record, (3) standardized work flow and responsibility, and (4) automated forwarding of results to providers. We measured the proportion of patients due for cholesterol testing who had it performed within 1 week of their clinic visit and the proportion of patients in our population who achieved low-density lipoprotein (LDL) cholesterol control at baseline and for 2 years after improved monitoring. The proportion of visits in which cholesterol monitoring was completed when indicated improved from 80% to 98% within 8 months and was sustained for more than 1 year. The number of patients with controlled LDL (<130 mg/dL, 3.3 mmol/L) improved from 44 (71%) of 62 at the start of our project to 58 (94%) of 62 (P = .002) at an average follow-up of 24 months. Using quality improvement and health information technology, we achieved sustained, reliable and efficient personalized monitoring of cholesterol and 11 other tests. This approach enabled substantial improvement in LDL cholesterol control. Structured methods of system redesign that leverage information technology systems hold promise for rapidly achieving reliable individualized care in other settings.

De novo therapy with everolimus and reduced‐exposure cyclosporine following pediatric kidney transplantation: A prospective, multicenter, 12‐month study

Prospective data regarding the de novo use of everolimus following kidney transplantation in children are sparse. In a prospective, 12-month, single-arm, open-label study, pediatric kidney transplant patients received everolimus (target trough concentration ≥3ng/mL) with reduced-exposure CsA and corticosteroids, with or without basiliximab induction. Sixteen of the 18 patients completed the study on-treatment. Age range was 2-16yr (mean 10.9yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12months post-transplant. There were no cases of BPAR, graft loss, or death during the study. Protocol biopsies were performed at month 12 in seven patients, with subclinical (untreated) acute rejection diagnosed in one case. Mean (s.d.) estimated GFR (Schwartz formula) was 98 (34)mL/min/1.73m(2) at month 12. Three patients experienced one or more serious adverse events with a suspected relation to study medication. One patient discontinued study medication due to post-transplant lymphoproliferative disease (5.6%). Everolimus with reduced-dose CsA and corticosteroids achieved good efficacy and renal function and was well tolerated in this small cohort of pediatric kidney transplant patients. Controlled trials are required to answer remaining questions about the optimal use of everolimus in this setting.

The immediate postoperative complications and outcomes of kidney transplantation in children

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

A Randomized Trial of Sirolimus-Based Graft Versus Host Disease (GVHD) Prophylaxis After Hematopoietic Stem Cell Transplantation (HSCT) in Selected Patients with CR1 and CR2 ALL: Results From Children's Oncology Group Study ASCT0431

Abstract 837Based upon demonstrated activity of mTOR inhibitors in preclinical models of ALL and a promising pilot study, we hypothesized that the use of sirolimus added to a standard GVHD prophylaxis regimen would decrease relapse and improve survival after HSCT for children with high-risk CR1 and CR2 ALL. The COG performed a randomized phase III trial comparing tacrolimus/methotrexate (tac/mtx) with tac/mtx plus sirolimus. Sirolimus was initiated on day 0 of transplant and continued at therapeutic levels for 6 months. All patients received a preparative regimen consisting of fractionated TBI (1200–1320 cGy), and cyclophosphamide (60mg/kg × 2) +/− thiotepa (5mg/kg × 2) or VP-16 (1500mg/m2). Patients with primary induction failure who attained CR, hypodipoid ALL (<44 chromosomes), and Ph+ ALL were eligible for HCT in CR1 (intermediate risk); eligible CR2 patients included B-lineage with early bone marrow (BM) relapse (<36m from diagnosis) or T-lineage with BM relapse at any time (high risk, HR) and B-lineage with late BM relapse or isolated extramedullary relapse occurring <18m from diagnosis (intermediate risk, IR). HLA-matched sibling donors, 7–8/8 HLA matched related or unrelated donors, and 4–6/6 HLA matched cord blood stem cell sources were allowed. Randomization was stratified by donor type and relapse risk group. Events included relapse and treatment related mortality (TRM); the study was designed to enroll 259 patients to detect a two-year event free survival difference of 16% with 80% power. Results: A total of 146 patients enrolled, with 142 providing data to the analysis. As of July 1, 2011, there were 27 events in the 69 control arm patients and 31 events in the 73 experimental arm patients. The study was closed on May 10, 2011 when a stopping rule for futility of the primary endpoint (improved EFS) was met. The rates of grade III–IV acute GVHD, relapse, and TRM were 22%, 28% and 12% in control and 15%, 29%, and 14% in experimental arm patients (p=NS). Rates of CMV reactivation, venoocclusive Disease (VOD), and transplant associated microangiopathy (TAM) were 19%, 9%, and 1% in control arm patients and 12%, 17%, and 8% in experimental arm patients (p=0.26, 0.13, 0.10, respectively). Multistate modeling results indicate that the treatment group experienced less grade 2 to 4 aGVHD, but relapse rates in aGVHD patients were a quarter of those in non-aGVHD patients (p=<.001) while TRM rates were 1.5 times that of patients with no or grade I aGVHD (p=NS, see table). Survival after sibling donor transplantation was identical to URD transplantation. There was a trend toward increased risk of relapse in recipients of cord blood (p=0.14); further analysis of HLA type, pre-HSCT minimal residual disease (MRD), and patient risk is underway to clarify this finding.NaGVHD (III–IV)RelapseTRM1 year EFSaGVHD (II–IV) not present9333 (31%)10 (11%).45a (.32–.61)aGVHD (II–IV) present497 (15%)8 (16%).79a (.60–.89)P value<0.0010.38Matched Sib7513 (17%)20 (27%)5 (7%).58 (.42–.71)URD/Other RD387 (18%)7 (18%)7 (18%).54 (.32–.71)Cord296 (21%)13 (45%)6 (21%).33 (.16–.51)P value0.720.140.30 Conclusions:The addition of sirolimus to tac/mtx resulted in a trend toward higher rates of non-fatal TAM and VOD, but identical rates of severe VOD and TRM. There was a lower rate of grade II–IV aGVHD in the experimental arm, but no decrease in relapse. For the combined cohort, grade II–IV acute GVHD was associated with significantly less relapse and improved survival, suggesting that GVL is important in decreasing relapse after HSCT for pediatric ALL. The cytotoxic effect of sirolimus against ALL was insufficient to decrease relapse when given to very high risk ALL patients after HSCT as part of GVHD prophylaxis, possibly because of the offsetting effect of decreasing GVL. Disclosures:Off Label Use: The trial used sirolimus for graft vs. host disease prophylaxis in children. Sirolimus is approved for kidney transplantation in children. Borowitz:BD Biosciences: Research Funding. Grupp:Children’s Hospital of Philadelphia: Patents & Royalties.

The effect of timing of the first kidney transplantation on survival in children initiating renal replacement therapy

Controversy exists concerning the timing of the first kidney transplantation for children who need to start renal replacement therapy (RRT). Our aim was to estimate the effect of timing of the first transplantation on patient survival in children, for the first time also taking into account the mortality on dialysis before transplantation. We included 2091 patients who started RRT between the age of 3 and 18 years in the period 1988-2007, from 13 European renal registries. A multistate model was used to simulate patient survival assuming (i) pre-emptive transplantation, (ii) transplantation after 1 or 2 years on dialysis and (iii) remaining on dialysis. Over the 20-year period, the highest 8-year survival probabilities were achieved in children transplanted pre-emptively {living donor (LD): 95.9% [95% confidence interval (CI): 93.1-98.8], deceased donor (DD): 95.3% (95% CI: 90.9-99.9)} rather than after 2 years of dialysis [LD: 94.2% (95% CI: 91.6-96.8), DD: 93.4% (95% CI: 91.0-95.9)], although these differences were not statistically significant. Even after taking mortality on dialysis into account, the potentially negative effect of postponing transplantation for 1 or 2 years was relatively small and not statistically significant. Therefore, if pre-emptive transplantation is not possible, starting RRT with a short period of dialysis and receiving a transplant thereafter seems an acceptable alternative from the perspective of patient survival.