Stable long‐term renal function after pediatric liver transplantation

Herlenius G, Hansson S, Krantz M, Olausson M, Kullberg‐Lindh C, Friman S. Stable long‐term renal function after pediatric liver transplantation.
Pediatr Transplantation 2010: 14:409–416. © 2010 John Wiley & Sons A/S. Abstract: Long‐term exposure to calcineurin inhibitors increases the risk of CKD in children after LT. The aims of this study were to study renal function by measuring GFRm before and yearly after LT, to describe the prevalence of CKD (stage III: GFR 30–60 mL/min/1.73 m²) and to investigate if age and underlying liver disease had an impact on long‐term renal function. Thirty‐six patients with a median age of 2.9 years (0.1–16 yr) were studied. Median follow‐up was 6.5 (2–14 yr). GFRm decreased significantly during the first six months post‐transplantation with 23% (p < 0.001). Thereafter renal function stabilized. At six months, 17% (n = 5) of the children presented CKD stage III and at five yr the prevalence of CKD III was 18% in 29 children. However, in 13 children with a 10‐year follow‐up it was 0%. None of the children required renal replacement therapy after LT. When analyzing renal function of those children younger than two yr (n = 14) and older than two yr (n = 17) at the time of transplantation, we found that in both cohorts the filtration rate remained remarkably stable during the five‐yr observational period. However, there was a statistically significant (p < 0.05) difference in the percentual decrease in GFRm between the groups during the first six months after LT 13% and 31%, respectively. Baseline GFRm according to diagnosis did not differ between the groups. During the first six months after LT, patients transplanted for hepatic malignancy (n = 6) and those with metabolic liver disease (n = 4) had a percentage loss of GFRm of 32% and 35%, respectively. The corresponding loss of GFRm in patients with other diseases was 10‐19%. Six months post‐transplantation mean GFRm in the group with malignant liver disease was 65 ± 15 mL/min/1.73 m² and in the group with other diseases (n = 24) 82 ± 17 mL/min/1.73 m² (p < 0.05). At one, three and five yr post‐transplantation there was no longer a statistically significant difference between these cohorts. Our findings suggest that there can be a long‐term recovery of renal function after LT in children.     

Basiliximab with delayed introduction of calcineurin inhibitors as a renal‐sparing protocol following liver transplantation in children with renal impairment

Renal impairment is frequently compromised in patients with end‐stage liver disease and is associated with increased long‐term mortality post‐LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal‐sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre‐LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m² vs. 144 mL/min/1.73 m²; p = 0.56) or at 5–8 yr following LT, (129 mL/min/1.73 m² vs. 130 mL/min/1.73 m²; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal‐sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long‐term kidney function.     

Outcomes and predictive factors of pediatric kidney transplants: An analysis of the Thai Transplant Registry

As universal coverage for pediatric kidney transplantation (KT) was introduced in Thailand in 2008, the number of recipients has been increasing. We evaluated predictive factors for graft failure to understand how to improve clinical outcomes in these children. Using data obtained from the National Transplant registry, we assessed the risk of graft failure using the Kaplan–Meier method and Cox proportional hazards regression. Altogether, 201 recipients aged <21 yr at the time of KT were studied. Living donors (LD) were significantly older than deceased donor (DD). Mean cold ischemia time of DD was 17 h. The mean donor glomerular filtration rate (GFR) was 84.0 mL/min/1.73 m². Induction immunosuppressive therapy was administered more frequently in DD than in LDKT. Delayed graft function (DGF) occurred in 36 transplants. Over 719 person years of follow‐up, 42 graft failures occurred. Graft survival at one, three, and five yr post‐transplant were 95%, 88% and 76%, respectively. Two factors independently predicted graft failure in multivariate analysis. The hazard ratios for graft failure in patients with DGF and in patients with donor GFR of ≤30 mL/min/1.73 m² were 2.5 and 9.7, respectively. Pediatric recipients should receive the first priority for allografts from young DD with a good GFR, and DGF should be meticulously prevented.     

Two decades of pediatric kidney transplantation in a multi‐ethnic cohort

Muneeruddin S, Chandar J, Abitbol CL, Seeherunvong W, Freundlich M, Ciancio G, Burke GW, Zilleruelo G. Two decades of pediatric kidney transplantation in a multi‐ethnic cohort.
Pediatr Transplantation 2010: 14:667–674. © 2010 John Wiley & Sons A/S. Abstract: This study evaluated a 20‐yr experience in kidney transplantation in children from a predominantly Hispanic community. A retrospective analysis was carried out in children who received kidney transplants from 1985 to 2005. Of 124 kidney transplants, 81 (65%) were from LD. Racial distribution was Hispanic (48%), followed by AA (24%) and Caucasian (26%). First yr allograft survival was similar in LD and DD and significantly better in LD until seven yr post transplant. eGFR <60 mL/min/1.73 m² at one yr post transplant was associated with a median allograft survival of 3.3 yr, compared to 16 yr in those with eGFR ≥ 60 mL/min/1.73 m² (p < 0.0001). Graft loss in the first five yr was from non‐adherence, recurrence of disease, and infections. Those of AA race were more likely to receive a DD and have low socioeconomic status and the poorest median allograft survival compared to Hispanics and Caucasians (6 vs. ≥15 yr; p < 0.001). In conclusion, this predominantly Hispanic cohort emphasizes the disadvantaged profile of AAs compared to other racial groups. Strategies to improve supportive services and living donations in minority populations need to be developed. Long‐term renal allograft survival is achievable if GFR is maintained >60 mL/min/1.73 m².     

Renal function evaluated by measured GFR during follow-up in pediatric liver transplant recipients

Abstract:  Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus-based immunosuppressive regimen. GFR was measured using 99 mTc-DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post-transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m²) to one yr post-transplant (112 mL/min/1.73 m²) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post-transplant. Although 13 (22%) patients developed renal dysfunction post-transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus-based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium-term. The Schwartz formula is inaccurate in determining GFR in this patient group.     

Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: a retrospective analysis

Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Among others, chronic calcineurin inhibitor toxicity (CNI) contributes to the development of CAN. Therefore, reduction in CNI dosage may delay the development of CAN, leading to longer graft survival. It was the aim of the present retrospective analysis to investigate the effect of mycophenolate mofetil (MMF) addition with subsequent cyclosporine A (CSA) reduction on renal function in pediatric kidney allograft recipients. Seventeen patients (aged 8.3-17.6 yr) with monotherapy with CSA and progressive loss of renal function at a median of 3.4 yr after kidney transplantation were enrolled. After at least three months of MMF treatment, CSA dosage was stepwise reduced to trough levels of 100, 80, and 60 ng/mL. In all patients, introduction of MMF prevented a further decrease of glomerular filtration rate (GFR). The mean GFR 12 months before study enrollment was 96.1+/-24.5 and 71.0+/-21.0 mL/min/1.73 m2 at start of MMF. After introduction of MMF and unchanged CSA dosage GFR was stabilized to 71.1+/-23.8 mL/min/1.73 m2. After CSA reduction to trough levels of 60 ng/mL, GFR was slightly ameliorated up to 76.3+/-24.1 mL/min/1.73 m2. Within the follow-up period, one borderline rejection occurred in a patient in whom the CSA trough level was 60 ng/mL since seven months. In pediatric kidney allograft recipients with progressive loss of renal function reduction of CSA after introduction of MMF may stabilize and even slightly ameliorate renal function.     

The profile of renal function over time in a cohort of pediatric heart transplant recipients

Abstract:  To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post-transplant was normal (94 mL/kg/1.73 m²). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m²) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m². Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.     

Single‐center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization

Our center has offered thymoglobulin induction with steroid minimization to our pediatric renal transplant patients for the last 10 yr. Steroid minimization or avoidance has shown favorable results in survival, kidney function, and growth in previous studies of pediatric patients. We report our experience with this protocol over the past 10 yr with respect to patient/graft survival, acute rejection episodes, renal function, linear growth, bone density, cardiovascular risk factors, and opportunistic infections. A retrospective chart review was performed for pediatric renal transplant patients on the steroid‐minimized protocol between January 2002 and December 2011 on an intention to treat basis. Patient demographics, height, weight, serum creatinine, iGFR, biopsies, and survival data were collected. Height and weight z‐scores were calculated with EpiInfo 7, using the CDC 2000 growth charts. Survival was calculated using Kaplan–Meier analysis. eGFR was calculated using the original and modified Schwartz equations. Forty‐four pediatric patients were identified, aged 13 months to 19 yr. Five‐yr survival was 95.5% for males and 94.4% for females. Only five patients had biopsy‐proven ACR, two of which were at more than 12 months post‐transplantation. Height delta z‐scores from transplant to one, three, and five yr were 0.34, 0.38, and 0.79, respectively. Weight delta z‐scores from transplant to one, three, and five yr were 0.87, 0.79, and 0.84, respectively. Mean original Schwartz eGFR was 84.3 ± 15.8 mL/min/1.73 m², modified Schwartz eGFR was 59.3 ± 11.5 mL/min/1.73 m², and iGFR was 64.2 ± 8.5 mL/min/1.73 m² at three yr. Of 18 subjects who had a bone density exam, none had a z‐score less than ?2 on DEXA exam at one‐yr post‐transplantation. Fifty‐one percent of patients were on antihypertensives at the time of transplant compared with 43% at one‐yr post‐transplantation. Three yr post‐transplantation, the average LDL was <100 mg/dL, and average total cholesterol was <200 mg/dL. There were no clinical episodes of EBV or CMV infection. A steroid‐minimized protocol with thymoglobulin induction is safe and provides favorable improvement in linear growth, stable graft function, stable or improved cardiovascular risk factors, and normal bone density in pediatric renal transplant patients.     

Bilateral native nephrectomy reduces systemic oxalate level after combined liver‐kidney transplant: A case report

Primary hyperoxaluria type 1 (PH1) is a rare liver enzymatic defect that causes overproduction of plasma oxalate. Accumulation of oxalate in the kidney and subsequent renal failure are fatal to PH1 patients often in pediatric age. Combined liver and kidney transplantation is the therapy of choice for end‐stage renal disease due to PH1. Levels of plasma oxalate remain elevated for several months after liver transplantation, as the residual body oxalate is slowly excreted. Patients with persistent hyperoxaluria after transplant often require hemodialysis, and accumulation of residual oxalate in the kidney can induce graft dysfunction. As the native kidneys are the main target of calcium oxalate accumulation, we postulated that removal of native kidneys could drastically decrease total body oxalate levels after transplantation. Here, we report a case of bilateral nephrectomy at the time of combined liver‐kidney transplantation in a pediatric PH1 patient. Bilateral nephrectomy induced a rapid decrease in plasma oxalate to normal levels in less than 20 days, compared to the several months reported in the literature. Our results suggest that removal of native kidneys could be an effective strategy to decrease the need for hemodialysis and the risk of renal dysfunction after combined liver‐kidney transplantation in patients with PH1.     

Renal function assessment in child and adolescent heart transplant recipients during routine cardiac catheterization

CKD identification after pediatric heart transplantation (PHT) is limited by inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol in PHT recipients and that the CKiD formula provides a better estimate of GFR than other estimating equations. A cross‐sectional study of PHT recipients, ages 2–18 yr, undergoing coronary angiography was undertaken. The angiography dose of iohexol was divided by the area under the curve from three iohexol levels post‐infusion to calculate GFR. Agreement between iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects, median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5) mL/min/1.73 m²; 16 (52%) had an iGFR <90 mL/min/1.73 m². The full CKiD formula (mean eGFR 88.9, s.d. 14.9) had low bias (?5.0), narrowest 95% limits of agreement (?42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest correlation coefficient (0.576) relative to iGFR. We describe a novel modified iohexol clearance method to assess GFR after PHT. Over half of the cohort had an iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to bias, accuracy, and correlation.     

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 ≥3 ng/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 2–16 yr (mean 10.9 yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12 months 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/1.73 m² 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.     

Estimated one-yr glomerular filtration rate is an excellent predictor of long-term graft survival in pediatric first kidney transplants

Acute rejection episodes following pediatric renal transplantation have been progressively reduced by recent immunosuppressive regimens. Nevertheless, grafts continue to fail over time and surrogate parameters for long-term RGS are lacking. We investigated post-transplant renal function within the first yr as an independent predictor of long-term RGS in 104 pediatric first kidney transplant recipients (mean age 11.1 +/- 3.9 yr; mean follow-up 8.3 +/- 3.5 yr) transplanted between January 1989 and December 2000. GFR was assessed by use of the Schwartz formula at 30 days and six and 12 months after transplantation, respectively. Patients were further stratified at all times according to GFR: (i) GFR<45 mL/min/1.73 m(2), (ii) GFR 45-80 mL/min/1.73 m(2), and (iii) GFR>80 mL/min/1.73 m(2). Cox regression analysis including factors potentially influencing long-term RGS, e.g., age, gender, transplant yr, HLA-mismatch, underlying renal disease, clinical acute rejection, absolute GFR as well as the change in GFR within the first yr was performed. Graft failure occurred in 24 out of 104 patients (23%) 6.2 yr (mean) after transplantation corresponding to a cumulative five-yr graft survival of 87.5%. GFRs at 30 days and six and 12 months were significantly associated with long-term RGS in the univariate cox regression analysis (GFR at 30 days, p = 0.045; GFR at six months, p = 0.004; GFR at 12 months, p < 0.001). None of the other variables were significant parameters of correlation. Multivariate cox analysis revealed a GFR below 45 mL/min/1.73 m(2) at 12 months after transplantation as the only independent predictor of long-term RGS (hazard ratio 55.9, 95% CI 5.29-591, p = 0.001). GFR at 12 months post-transplant is an excellent surrogate parameter for long-term RGS in children. This parameter might be useful as a primary end-point in short-term pediatric clinical trials.     

Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1

In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.     

Intra-patient variability in tacrolimus trough concentrations and renal function decline in pediatric renal transplant recipients

Prytula AA, Bouts AH, Mathot RAA, van Gelder T, Croes LK, Hop W, Cransberg K. Intra‐patient variability in tacrolimus trough concentrations and renal function decline in pediatric renal transplant recipients. Abstract: High intra‐patient variability in TCL exposure is a risk factor for allograft loss and late acute rejection. We hypothesized that a higher intra‐patient variability leads to a faster decline in GFR in pediatric renal transplant patients and that adolescents have a higher intra‐patient variability due to poorer adherence. We included 69 children aged 3.5–18 yr who had undergone renal transplantation between April 1996 and May 2009 in two pediatric nephrology centers in the Netherlands. We analyzed TCL trough concentrations over a period of one yr and calculated TCL trough concentrations variability using VC. We investigated the correlation between the TCL trough concentrations variability and the decline in estimated GFR over four yr. The median intra‐patient variability in TCL concentrations was 30.1% (range 8.6–77.6) and the mean GFR slope ?3.8 mL/min/1.73 m²/yr. The VC correlated neither with the GFR slope, nor with the patients’ age. However, children with late acute rejection had higher VC (p = 0.045). We were unable to provide evidence that a high variability in TCL exposure leads to a faster decline in renal function, although children with late acute rejection have a higher variability in TCL exposure. Adolescents do not have a higher intra‐patient variability in TCL trough concentrations than younger children.     

Renal function after combined liver‐kidney transplantation: A longitudinal study of pediatric and adult patients

It has been proposed that the liver protects the kidney in CLKT. However, few studies have examined long‐term renal function after CLKT and contrasted renal function of CLKT patients to KT patients beyond one year after transplantation. We studied long‐term renal function of CLKT patients and compared renal function of CLKT patients to KT patients between one and five years after transplantation. Patients who underwent CLKT between 1993 and 2011 were included (n = 34; 11 children and 23 adults). Ninety‐six (27 children and 69 adults) KT patients were selected as controls. GFR was estimated (eGFR) and measured (mGFR) with ⁵¹Cr‐EDTA clearance. Mean mGFR was 63 at one and 70 at ten years after pediatric CLKT. Mean eGFR was 75 at one and 50 at ten years after adult CLKT. Difference in mean mGFR between pediatric CLKT and KT patients was 8 (95% CI ?7 to 23) and 11 (95% CI ?4 to 26) at one and five years after transplantation, respectively. Difference in mean eGFR between adult CLKT and KT patients was 8 (95% CI ?5 to 20) and 1 (95% CI ?10 to 12) at one and five years after transplantation, respectively. Longitudinal changes in GFRs were somewhat similar in CLKT and KT patients in both age‐groups but pediatric CLKT patients had on average higher GFRs than pediatric KT patients. In long‐term follow‐up, renal function remains stable in pediatric CLKT patients but declines in adult CLKT patients.     

Alemtuzumab induction with tacrolimus monotherapy in 25 pediatric renal transplant recipients

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1–19 yr (mean 14 ± 4.1 yr). Time of follow‐up was 7–51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post‐transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m², respectively. One, two, and three‐yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty‐four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0–1.8 mg/dL). One graft was lost four yr after transplantation due to medication non‐compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short‐ and mid‐term patient and graft survival in low‐immunologic risk pediatric renal transplant recipients.     

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from CNIs to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy proven CAN.     

Long-term glomerular filtration rate following pediatric liver transplantation

In adult patients a significant proportion of chronic renal failure after liver transplantation (LTX) has been described. This was attributed mainly to nephrotoxicity caused by Calcineurin inhibitors (CNI). If these results are transferable to pediatric patients was the aim of this study. Forty-five pediatric patients with a LTX performed between 1988 and 2003 were evaluated. Glomerular filtration rate was calculated using the Schwartz formula (calculated GFR (cGFR) (mL/min/1.73 m2) = kx height (cm)/serum creatinine (mg/dL)). Median age at LTX was 4 yr (range 0.3-18.1). Pretransplant median cGFR was significantly elevated with 157.5 mL/min/1.73 m2. Within the first 3 months after LTX median cGFR normalized to a median value of 102.7 (p < 0.05 vs. pretransplant cGFR). During long-term follow-up median cGFR remained stable with calculated values of 108.0 two years and 112.6 five years after transplantation. Using a linear and an exponential one compartment mathematical modeling of renal function the calculated GFR was stable even for very long observation times (n > 10 yr). Liver insufficiency prior to transplantation was associated with glomerular hyperfiltration. After successful liver transplantation cGFR normalized within the first 3 month and, in contrast to the reported GFR impairment in adult liver transplant recipients, remained stable, even in long-term follow-up.     

Successful transplantation of four kidney grafts from two small pediatric donors with anuric acute renal failure into adult recipients

Background

Kidneys from infants with anuric acute kidney injury (AKI) only rarely get accepted for transplantation despite encouraging data that such kidneys can have very good long-term outcome.

Methods

We report the transplantation of four kidney grafts from two pediatric donors (3 and 4 years) with anuric acute kidney injury as single kidneys into four adult recipients.

Results

All grafts gained function within 14 days posttransplantation, only one recipient needed dialysis after transplantation. None of the recipients suffered from surgical complications. One month after transplantation, all recipients were free of dialysis. Estimated glomerular filtration rates (eGFR) 3 months after transplantation were 37, 40, 50, and 83 mL/min/1.73 m². eGFR increased further through month 6, reaching 45, 50, 58, and 89 mL/min/1.73 m².

Conclusion

These cases highlight the feasibility of successful transplantation of single pediatric kidney grafts into adult recipients despite anuric AKI of the donor.     

Short-term pediatric renal transplant survival: Blood pressure and allograft function

Hypertension is prevalent after renal transplantation (Tx) and associated with graft failure in children and adults. However, the effect of blood pressure (BP) on short-term renal allograft function is uncertain. We assessed the associations among BP pretransplant, and 3 months and 1 yr post-transplant, and 1-yr post-transplant measured glomerular filtration rate (mGFR) in 61 children with a functioning graft. The GFR was determined using a single intravenous (i.v.) injection of Optiray 350(R). Data were collected between January 1994 and January 2000. The mean mGFR 1 yr after renal transplant was 63.6 +/- 19.9 mL/min/1.73 m2 in 26 live donor recipients and 50.8 +/- 23.3 mL/min/1.73 m2 in 35 cadaveric donors (p = 0.029). Correlation analysis showed significant negative associations of 1-yr mGFR with systolic blood pressure (SBP) and diastolic blood pressure (DBP) 3 months after renal Tx (r = - 0.58, p < 0.0001 and r = - 0.50, p < 0.0001, respectively), and with SBP (r = - 0.37, p = 0.003) and DBP (r = - 0.32, p = 0.01) 1 yr after renal Tx. Multi-variate regression analysis showed that the SBP 3 months after Tx (p < 0.001), number of acute rejections (p = 0.002), donor age (p = 0.02), and cold ischemia time (p = 0.03) were independent predictors for the 1-yr mGFR. These results indicate that a higher SBP in the first few months post-renal Tx is associated with decreased renal allograft function in children 1 yr post-Tx.