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There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group ( p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Butani and Tancredi.)

Infections remain the most common cause of hospitalization after kidney transplantation, contributing to significant post-transplant morbidity and mortality. There is a growing body of literature that suggests that immunoglobulins may have a significant protective role against post-transplant infections, although the literature remains sparse, inconsistent, and not well publicized among pediatric nephrologists. Of great concern are data indicating a high prevalence of immunoglobulin abnormalities following transplantation and a possible link between these abnormalities and poorer outcomes. Our educational review focuses on the epidemiology and risk factors for the development of immunoglobulin abnormalities after kidney transplantation, the outcomes in patients with low immunoglobulin levels, and studies evaluating possible interventions to correct these immunoglobulin abnormalities., (© 2022. The Author(s).)

Background: There are conflicting data on long-term outcomes of pediatric LURD renal Txs compared to Txs of kidneys from other donor sources., Methods: An analysis of the OPTN database was conducted in children (<18 years) who had received their 1st kidney-only Tx between January 1, 2000, and September 30, 2021. The primary outcome measure was time to graft failure or death. Cox event history regression model for time to primary outcome, categorized by donor source and adjusting for confounders was performed., Results: Of the 12 089 subjects, 327 (2.7%) received kidneys from LURDs, 4349 (36%) from LRDs and 7413 (61%) from DD. One year graft failure rate was 3.56%. On regression analyses, compared to LRD kidney recipients, LURD recipients had comparable graft survival (graft failure AHR 1.15, 95th percentile confidence interval 0.87-1.51; p .31) and DD recipients had lower graft survival (graft failure hazard ratio 1.26, 95th percentile confidence interval 1.10-1.43; p < .001). When using living unrelated kidney recipients as the reference group, DD kidney recipients had comparable graft survival, with a wide confidence interval (hazard ratio for graft failure 1.09; 0.83-1.43, p .53)., Conclusions: Pediatric LURD kidney recipients have comparable graft survival to LRD kidney recipients; DD kidney recipients had the poorest survival. Our study, the largest to date, should encourage centers to embrace non-commercial living-unrelated transplantation as a viable option for children, preferable to DD kidneys., (© 2022 Wiley Periodicals LLC.)

Objective: To determine whether pre-transplant body mass index (BMI) affects renal allograft function and survival in pediatric renal transplant recipients., Study Design: This is a retrospective cohort study using the Organ Procurement and Transplantation Network data from 2000 to 2013 to compare time to total allograft loss (allograft failure or death), prevalence of delayed graft function, prevalence of acute rejection, and estimated glomerular filtration rate (eGFR) post-transplant in pediatric renal transplant recipients categorized by BMI z-score., Results: A total of 8804 kidney transplant recipients met our inclusion criteria, and of those, 6% were underweight, 14% were overweight, and 17% were obese pre-transplant. The adjusted hazard ratio (HR) for allograft failure was significantly higher for obese recipients compared to normal weight recipients (HR 1.25, 95% CI 1.1, 1.42); for every 1 point increase in BMI z-score, there was a 7% increased hazard of allograft failure (HR 1.07; 95% CI 1.03-1.1, p < 0.001). The prevalence of delayed graft function and acute rejection increased with higher BMI z-score category; however, this difference did not reach statistical significance. eGFR at 1 and 5 years post-transplant decreased with higher BMI z-score although it was only statistically significant at 1 year., Conclusions: Obesity is prevalent in pediatric renal transplant recipients, and obese, but not overweight or underweight, pediatric renal transplant recipients have an increased risk of allograft failure. Implementation of effective obesity interventions in pediatric renal transplant recipients is of critical importance to improve longevity of the renal allograft.

Objective: To determine whether renal transplantation survival is similar in children receiving pediatric en bloc kidneys compared with those receiving standard deceased donor kidneys., Study Design: We compared time to allograft failure and estimated glomerular filtration rate (eGFR) in pediatric recipients of en bloc and standard criteria deceased donor renal transplants using Organ Procurement and Transplantation Network data for 2000-2013. Cox regression analysis was used to compare time to allograft failure, and the Student t test was used to compare eGFR., Results: A total of 6882 recipients met the study inclusion criteria; 1.8% received an en bloc transplant. The adjusted hazard for allograft failure was similar for recipients of en bloc kidneys compared with standard criteria kidneys (hazard ratio, 1.15; 95% CI, 0.83-1.59; P = .41). The median wait time for transplantation was significantly shorter for recipients of en bloc kidneys (157 days vs 208 days; P = .03). Moreover, eGFR was superior for recipients of en bloc kidneys up to 5 years post-transplantation., Conclusion: Transplantation of en bloc pediatric kidneys should be considered a viable option for pediatric recipients and may afford unique benefits by reducing wait times and promoting preservation of graft function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

AMR is increasingly being recognized as an important cause of renal allograft injury, contributing to significant morbidity and graft loss. There are few controlled trials and no well-established treatment guidelines for AMR in renal transplant recipients. We retrospectively reviewed the outcome of four pediatric renal transplant recipients on a steroid minimization immunosuppression protocol treated with bortezomib for elevated DSA and acute AMR from 2012 to 2013. All patients received four doses of bortezomib 1.3 mg/m2 given on days one, four, eight, and 11. All patients also received other treatments prior to bortezomib, which may have included rituximab, methylprednisolone, plasmapheresis, and/or IVIg. While bortezomib in addition to other therapies significantly decreased DSA titers, DSA remained very elevated months after treatment. All four patients had immediate improvement or stabilization of renal function but one eventually lost her graft. There were no adverse events related to bortezomib six months after treatment., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the contemporary era of potent immunosuppressive regimens, previously encountered signs of renal allograft rejection such as fever and hematuria are rarely encountered. We report a teenager with severe recurrent acute humoral and cellular rejection whose presenting feature was gross hematuria with the presence of blood clots in the urine. We want to highlight that severe rejection even in the setting of modern immunosuppressive drugs can present as gross hematuria. Contrary to conventional wisdom that gross hematuria with the presence of blood clots in the urine is indicative of pathology in the renal collecting system, a parenchymal disease process should also be considered in renal transplant recipients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To determine the prevalence of hypoalbuminemia in children listed for renal transplantation and to evaluate the effect of pretransplant hypoalbuminemia on posttransplant outcomes., Study Design: Retrospective cohort analysis of children receiving their first kidney transplant in the US between January 2000 and December 2010 obtained through the Organ Procurement and Transplantation Network. The primary outcome measure was time to graft failure. Cox regression analyses were used to estimate the independent effect of serum albumin on event incidence., Results: Of the 6032 children who received transplants, 308 (5.1%) had a very low serum albumin level at registration; rates of transplantation in such children varied significantly across geographic regions (χ(2), P < .001) ranging from 2.1% to 8.7%. Serum albumin was inversely associated with graft failure; each 1-g/dL increase in serum albumin was associated with a 19% reduction in risk of graft failure (adjusted hazard ratio 0.81, 95% CI 0.75-0.88, P < .001)., Conclusions: Considerable regional variation exists in the US with respect to transplantation in children with hypoalbuminemia. Severe hypoalbuminemia is an independent risk factor for graft failure. Transplant centers as well as patients need to be aware of this risk and make informed decisions regarding the optimal timing of transplantation. Whether graft failure is a consequence of the low serum albumin or the reflection of a higher inflammatory milieu remains to be explored., (Copyright © 2014 Mosby, Inc. All rights reserved.)

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post-operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow-up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra-operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow-up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow-up, the median eGFR was 130 mL/min/1.73 m(2). The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long-term follow-up to monitor for complications, including hyperfiltration injury, is warranted., (© 2012 John Wiley & Sons A/S.)

SM protocols have increasingly gained acceptance owing to their favorable side effect profile with comparable cellular rejection rates. After encountering SM patients with AHR, we performed a case-control study to identify predictors associated with AHR in this cohort. Patients with (n = 4) and without (n = 19) biopsy proven AHR on a SM regimen were compared using the Student's t-tests. The median age at transplant was 13.8 yr. Compared to controls, the AHR cohort was older (15.9 vs. 12.1 yr, p = 0.01). Children with AHR had a lower mean tacrolimus trough level and were more likely to have a sub-therapeutic trough at six months (3.5 vs. 5.5 ng/mL, p = 0.05); mean MMF doses were lower at all times points except three months in the AHR group (not statistically significant). This occurred in spite of higher MPA trough levels at all study points in the AHR group (significant at 3 [p = 0.019] and 6 [p = 0.03] months). Children receiving a SM regimen have a lower safety net and may benefit from more intensive monitoring of tacrolimus exposure. MMF dose modifications based on MPA trough determinations should be resisted in the setting of SM., (© 2011 John Wiley & Sons A/S.)

Background: Adults receiving preemptive renal transplants have better allograft survival. Our study investigated differences in graft and patient survival based on need for, and duration of, pretransplant dialysis in pediatric renal transplant recipients., Methods: Data on pediatric kidney transplants from January 1995 to December 2000 from the Organ Procurement and Transplantation Network were included. Multivariable Cox proportional hazards analysis was performed to determine the effect of pretransplant dialysis on graft and patient survival., Results: Of 3606 transplants, 28% were preemptive, 38% followed pretransplant hemodialysis (HD), and 34% peritoneal dialysis (PD). The 1-year acute rejection rate was lowest for the preemptive group (36%) compared with the HD (45.5%; P=0.0002) and PD (44.2%; P=0.0008) groups. On multivariable analysis, an increased relative risk of graft failure was seen with, among other variables, deceased donor transplantation and acute rejection within the first year, but not with pretransplant dialysis. When analyzed separately by donor source, pretransplant dialysis had no effect on graft survival for deceased donor graft recipients, whereas for living donor recipients, the use and duration of pretransplant HD adversely affected pediatric renal graft survival in a linear manner. No such effect was seen with pretransplant PD., Conclusions: There is a linear increase in the risk of graft failure with the use of and increasing duration of pretransplant HD for living donor grafts. This indicates another reason to minimize the need for and duration of pretransplant HD in children with chronic kidney disease.

Background and Objectives: Corticosteroids are an important contributor to posttransplant hyperlipidemia. Since 2004, we have used a steroid minimization immunosuppression protocol. This study investigated the effect of steroid minimization on dyslipidemia in pediatric renal allograft recipients., Design, Setting, Participants, & Measurements: Children (<18 years) who underwent renal transplants at our center from January 2001 to January 2008 were studied. Data analyzed included age, gender, race, body mass index, cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and steroid dose. Data between the cohorts receiving maintenance steroids and steroid-minimization were compared using multivariable analyses. The primary outcome measures were the prevalence of, and the effect of steroid use, on dyslipidemia., Results: Twenty-nine patients were studied. Sixteen were receiving maintenance steroids, and 13 were on a steroid minimization regimen. Mixed effects analysis of covariance models demonstrated that at 1 month, children receiving maintenance steroids had higher cholesterol compared with the steroid minimization group. Statistically significant differences in total cholesterol were not seen at other time points. Similar findings were noted for the LDL cholesterol, LDL/HDL, and cholesterol/HDL ratios. At 1 month, the serum HDL cholesterol was substantially lower in the steroid minimization group. Differences in the HDL cholesterol levels remained significant throughout the first year., Conclusions: Steroid use is a significant independent risk factor for hypercholesterolemia during the first post-transplant month. The significance of lower HDL cholesterol among patients receiving steroid minimization needs further study and may be cause for concern.

Purpose: To determine the safety and efficacy of a novel steroid minimization protocol after renal transplantation at a single Northern California center., Introduction: We have previously reported our experience on the short-term outcomes in eight children using our steroid minimization protocol. Herein, we present our ongoing experience in using this regimen in 20 children., Methods: Children receiving immunosuppression with a steroid minimization protocol at our center from 1/04-12/08 (Group 2) were retrospectively compared with 20 controls (Group 1)., Results: At one-month follow-up, Group 2 was observed to have lower eGFR, hemoglobin, white cell count, and cholesterol. The incidence of adverse events during the first yr was comparable. Three patients in Group 1 displayed histological evidence of acute rejection, one patient in Group 2 developed humoral rejection; another patient in Group 2 had sub-clinical rejection. Surgical complications were observed in 20% of patients in both groups. While 10% of patients in Group 1 developed diabetes mellitus, none was observed in Group 2. Thirty and 40% of patients in Groups 1 and 2, respectively, suffered from infectious complications during the first yr., Conclusions: Our novel steroid minimization immunosuppression is safe in children and associated with no increased risk of rejection and infection., (Copyright (c) 2009 John Wiley & Sons A/S.)

As a result of the ongoing shortage in organ supply, en bloc renal transplantation from small donors has become more common for adult recipients with ESRD. However, because of concern for higher complication rates and sub-optimal outcomes, it is not being performed in every center, and data describing its use in pediatric recipients are even more limited. We retrospectively studied three patients who have undergone en bloc renal transplantation at our center. Median age at transplantation was 16.7 yr with a median follow-up of 1.2 yr. Donor age ranged from nine to 49 months with weight ranging from 10 to 22 kg. There were no post-operative thrombotic complications. All grafts showed increased renal size at follow-up by ultrasound. There was no clinical or histological rejection at last follow-up. To the best of our knowledge, this is the first report on the outcomes of en bloc kidney transplantation from pediatric donors into pediatric recipients. Based on our experience, albeit very limited, we feel that en bloc renal transplantation from young donors is an acceptable and safe procedure with low complication rates in pediatric recipients and should be given consideration to minimize wait times on the wait list and to improve quality of life., ((c) 2009 John Wiley & Sons A/S.)

Steroid-minimization regimens have gained tremendous popularity for renal Tx in the recent past since they are associated with lower metabolic complications and other adverse effects related to long-term steroid exposure. Most such protocols have been restricted to low-risk recipients due to the concern for acute rejection with steroid-minimization. Herein, we report our experience in managing a child who received a positive flow cytometry cross-match living donor kidney transplant with low titer DSA and was successfully managed using a steroid-minimization drug regimen. The purpose of our report is to make pediatric transplant care providers aware of the feasibility of using a steroid-minimization immunosuppression regimen even in children who have traditionally been perceived to be at higher risk for immunologic complications, allowing successful avoidance of steroid toxicity.

To determine the outcomes of pediatric renal transplant recipients who received immunosuppression consisting of early withdrawal of corticosteroids at a single Northern California center. Protocols using minimal steroid exposure have been recently reported in adult transplant recipients with successful results. We examined the outcomes of pediatric renal transplant recipients who were managed at our center using a protocol with very early discontinuation of steroids after renal transplantation. We retrospectively studied the medical records of all renal transplant recipients followed at the Children's Hospital at the University of California, Davis Medical Center from 01/2004 to 12/2005. All patients were less than 18 yr of age at the time of transplantation. The immunosuppressive protocol included three tapering daily doses of methylprednisolone, together with five doses of thymoglobulin followed by maintenance therapy with tacrolimus and MMF. Eight patients with equal numbers of males and females were transplanted during this time period. There were equal numbers of Caucasians, African-Americans, Hispanics, and Asians. A total of 37.5% (3/8) of the subjects received preemptive transplantation, 25% (2/8) received peritoneal, and 37.5% (3/8) received hemodialysis before transplantation. The median (range) age at transplantation was 12.3 (3.1-16.0) year with a follow-up of 1.7 (0.9-2.8) year. At one yr post-transplantation, 57% (4/7) of patients still required anti-hypertensives. Three children required erythropoietin supplementation after transplantation. The mean delta height standard deviation score at 12 months was 0.20 +/- 0.56. There were no episodes of clinical acute rejection. One patient switched from tacrolimus to sirolimus due to biopsy-proven CAN. No patient became diabetic or required hypoglycemic agents. Surveillance biopsies showed no subclinical acute rejection in any patient. Steroid-free immunosuppression is safe in children after renal transplantation. Larger number of patients and longer follow-up are required to further confirm the effectiveness and safety of immunosuppression with rapid steroid discontinuation.

Because of its narrow therapeutic index, monitoring of drug exposure is recommended for tacrolimus (T). Limited data are available on kinetics of T in children after transplantation. Our study investigated the correlation between T trough and the area under the time-concentration curve (AUC) in pediatric renal transplant recipients and investigated the effect of steroids. Data on T troughs and two h and four h post-dose concentrations over the first post-transplant year in 20 transplant recipients from August 2001 to June 2005 were analyzed. Patients were analyzed in two groups based on their use of steroids. Although the overall correlation between the troughs and AUC was good (r = 0.85, Pearson test), during the first month the correlation was poor in the cohort receiving steroids (r = 0.5) compared with those on a steroid minimization regimen (r = 0.9). In 85% of patients there was a discrepancy between the trough and AUC leading to errors in dose adjustment. In conclusion, although the overall correlation between T trough and AUC is good, it is suboptimal in the first post-transplant month in children receiving steroids. Because of large variation in exposure, we recommend AUC monitoring for T. Prospective studies are needed to determine the impact of more accurate monitoring of T exposure on outcomes.

With longer graft and patient survival, recurrent disease is becoming recognized as an increasingly important contributor to long-term graft loss in renal transplant recipients. However, patients may present for the first time in end-stage renal disease (ESRD) leading to uncertainty as to their underlying diagnosis and the risk of recurrence. The purpose of this study was to describe the features of children who presented for the first time in ESRD and to determine the predictive value of investigations in differentiating diseases with and without a recurrence risk. From 7/99 to 11/04, 13 children presented to our center in ESRD. Their median age was 13.3 yr; 77% were male. The majority were hypertensive (77%) and oligoanuric (69%). All had proteinuria (median urine protein to creatinine ratio [Up/c] 7.0), and 92% had microhematuria. Only seven had small kidneys on ultrasound. All children underwent a serologic work-up and six (46%) were biopsied. Of the 13 children, seven had a glomerular disease; in five the diagnosis was made on biopsy, in one on serologic testing and one by family history. Of the remaining six children, three had non-glomerular diseases: obstructive uropathy in one and primary hyperoxaluria type 1 in two, and 3 had an unknown disease. When patients with glomerular diseases were compared with those with non-glomerular diseases, the two predictors for glomerular disease were a lower serum albumin (p = 0.004) and a higher serum bicarbonate level (p = 0.01). Comparing patients with and without a risk of recurrence, there were no differences between the two groups in any of their demographic, clinical, or biochemical parameters by analysis of variance (including serum albumin or proteinuria). In summary, the vast majority of children presenting in ESRD have hematuria and proteinuria, even with non-glomerular diseases. The significant overlap in clinical features between patients with and without a risk of recurrence emphasizes the need for all children presenting in ESRD to be evaluated extensively so that disease recurrence after transplantation can be anticipated or even prevented.

Hyperlipidemia is common after renal transplantation (Tx) and contributes to the increased cardiovascular morbidity seen in the post-transplant period. Limited data are available on the utility of the statins in children after renal Tx. This 12-month prospective study was undertaken to determine the efficacy of pravastatin in reducing dyslipidemia after renal Tx in children and to determine predictors of dyslipidemia after Tx. From August 2001 to April 2004, all 17 newly transplanted pediatric renal transplant recipients at our center were preemptively treated with pravastatin from the immediate post-transplant period. Fasting lipid profiles were obtained at 1, 3, 6 and 12 months after Tx. Trends in the lipid profile were analyzed using the repeated measures general linear model (GLM). A historical cohort of pediatric renal-transplant recipients not treated with pravastatin was used as the control population. The mixed effects GLM was used for multivariable logistic regression analyses to determine the independent effect of age, pretransplant cholesterol (Chol), body mass index (BMI), creatinine clearance (CrCl), and corticosteroid and tacrolimus doses on the development of dyslipidemia. The mean age of the children at Tx was 8.7 yr. The GLM analysis showed that with time, there was a significant decline in the total Chol, serum triglyceride (TG), LDL and also HDL-Chol (p-value <0.05 for each). Compared with the controls, the mean serum Chol was lower at all time points post-transplant in the treated patients. However, despite treatment, the prevalence of hypercholesterolemia increased from 31% pretransplant to 53% at 1-month, but declined thereafter to 6% at 3 and 6 months and 0% at 1 yr. Multivariable regression analyses showed the prednisone dose, pretransplant Chol and age to be the most important risk factors for the development of dyslipidemia. No child developed complications related to therapy. In summary, pravastatin is safe in the post-transplant period in children and reduces serum Chol, LDL-Chol and TG. An unexpected finding in our study was the decline in HDL-Chol after Tx. Whether the preemptive use of the statins will result in lower cardiovascular morbidity, especially considering the concomitant reduction in HDL-Chol remains to be determined.

Pretransplant (Tx) inflammation is linked to adverse outcomes in adult Tx recipients but no such data exist for children. Our study evaluated the predictive value of three pre-Tx inflammatory markers: serum C-reactive protein (CRP), Neopterin (Neo) and interleukin (IL) 12, in determining outcome. Pre-Tx serum on 51 children (mean age 11 years) transplanted between 1985 and 2000 was analyzed. Data on other variables were abstracted from patient records. Primary end-points were graft survival and acute rejection (AR). Kaplan-Meier and log-rank statistics compared endpoints in patients at different quartiles for each marker. Cox regression analysis was used to determine the independent effect of the markers on the end-points. The mean CRP, Neo, and IL-12 were 1.3 mg/l, 1.78 ng/ml, and 123 pg/ml, respectively. The mean CRP, Neo, and IL-12 were not different between the patients with and without AR or graft loss (P > 0.4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles. Cox-regression analysis demonstrated no predictive value of any marker on outcome. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children, indicating that the pathogenesis of AR may be different in children.

Because of its lack of nephrotoxicity, the use of sirolimus, as an immunosuppressive agent, has increased considerably in solid-organ transplant (Tx) recipients. With its increased use, Tx professionals are encountering a variety of previously unreported side-effects such as angioedema and interstitial pneumonitis. We describe here the case of a pediatric renal Tx recipient who, while receiving sirolimus, developed a large pericardial effusion requiring pericardiocentesis. An extensive workup for an infectious etiology was performed; the only positive result was isolation of adenovirus type 2 from the patient's stool specimen. Following sirolimus dose reduction this child's effusion stabilized and has not recurred. The purpose of this report is to advise health-care professionals caring for Tx recipients about this potentially life-threatening complication associated with sirolimus. The role of adenovirus, if any, in contributing to the development of our patient's pericardial effusion is discussed herein.

Background: Little is known about the incidence and evolution of proteinuria as a complication of sirolimus rescue in children. This study describes pediatric renal transplant (Tx) recipients who were treated with sirolimus and who developed heavy proteinuria. Risk factors for the development of proteinuria and its time course are explored., Methods: Data at various time points after sirolimus introduction were abstracted from the records of children treated at the author's center. The repeated measures general linear model and the Student's paired t test were used to analyze changes in laboratory values over time., Results: Of the 13 children on sirolimus, 12 developed heavy proteinuria after a mean interval of 1 month. The mean urine protein (Up)-to-creatinine (c) ratio increased from 1.1 to a peak value of 3.9 (P=0.003) at 4.6 months after the start of sirolimus. Although not statistically significant, children on no calcineurin inhibitor (CNI) had a greater increase in the Up/c than those on low-dose CNI. At last follow-up, with the use of angiotensin receptor blockers (ARB), the Up/c declined to 2.2. No predictors could be identified for the development of proteinuria., Conclusions: Heavy proteinuria is common after the use of sirolimus as rescue therapy in children with renal Tx. Whether this is attributable to a toxic effect of the sirolimus itself or to lower CNI exposure is uncertain. Early detection of proteinuria is important to enable prompt intervention. Most children have a reduction in their Up/c with the use of ARB and can therefore be continued on sirolimus.

Renal transplant (Tx) recipients frequently develop hypercholesterolemia. Pravastatin (P) has been shown to be effective in adult renal Tx recipients, not only in reducing serum cholesterol, but possibly also in decreasing graft rejection. However, there are no data on the use of P in children following renal transplantation. We conducted a retrospective case-control study evaluating the safety and efficacy of P (10-20 mg/day) in reducing hypercholesterolemia, when used pre-emptively in the post-Tx period in seven children, compared with an historical control (C) group of nine children who had not received P. The two groups were comparable with respect to their demographics and in their pretransplant serum cholesterol. Compared with the C group, the mean serum cholesterol in the P group was lower at 3 months (159 mg/dL vs. 225 mg/dL), 6 months (134 mg/dL vs. 200 mg/dL), 9 months (134 mg/dL vs. 209 mg/dL), and 12 months (125 mg/dL vs. 195 mg/dL) (p < 0.005 for all, Student's two-tailed t-test). At 1 month only 43% of the P group had hypercholesterolemia compared with 67% of the controls; by 12 months this difference was even more significant (0% in the P group vs. 45% in the C group). None of the treated patients developed any adverse reactions. This study demonstrates that the pre-emptive use of P in pediatric renal Tx recipients appears to be effective in significantly reducing serum cholesterol. Whether this effect will translate into improved allograft and patient survival in the long term cannot be predicted at present and will require additional studies to evaluate.

The renal transplant (Tx) recipient is at risk for developing various complications including urolithiasis, the only manifestation of which may be hematuria. However, there are no data on the prevalence of microscopic hematuria in renal Tx recipients. The objective of our study was to determine the prevalence of microhematuria in our pediatric Tx patients and to investigate the causes of microhematuria. Records of all pediatric renal Tx recipients followed at our center from September 1999 to September 2000 were retrospectively reviewed; of the 21 patients, seven (33%) had persistent microscopic hematuria that was first noted 2.9 years post-Tx. Patients with and without hematuria had similar baseline characteristics. Only one patient had pre-existing hematuria that continued post-Tx. The etiology of hematuria in the other six patients was: recurrent IgA nephropathy (one patient), CMV nephritis (one patient), and unexplained (four patients). None had renal calculi or hypercalciuria. Three of the four patients with unexplained hematuria have chronic allograft nephropathy, and the fourth (original disease dysplasia) has hypocomplementemia. At their last follow-up, 5.3 years after onset of hematuria, all patients are alive with stable allograft function. In conclusion, microscopic hematuria is not uncommon in pediatric renal Tx recipients. While causes of post-Tx hematuria are diverse, stones are not commonly seen. Whether chronic allograft nephropathy per se can be implicated as a cause of hematuria remains to be determined. Renal biopsies should be considered at the onset of hematuria if proteinuria and/or deterioration in renal function are seen concomitantly, to look for recurrent or de novo glomerulonephritis.

Background: Laparoscopically procured live donor kidney grafts are increasingly transplanted into pediatric recipients. The safety and efficacy of this changed surgical practice are unknown., Hypothesis: Outcomes of laparoscopic vs open donor grafts in recipients 18 years and younger are equivalent., Design and Setting: Retrospective review at an academic tertiary care referral center., Patients: Eleven consecutive pediatric recipients of laparoscopically procured kidneys between April 1, 1997, and December 31, 2001, were pair matched for age with 11 recipients of openly procured kidneys between December 1, 1991, and March 31, 1997; the 22 adult donors were also studied., Main Outcome Measures: Recipients: surgical complications, graft function and survival. Donors: perioperative morbidity and length of hospital stay., Results: Twenty (91%) of 22 kidneys were donated by a parent of the recipient. In recipients of laparoscopically procured grafts, we observed significantly lower creatinine clearances and higher creatinine levels on days 1, 4, and 6, but by 1 month, graft function was similar in both groups. No significant differences in surgical complications, delayed function, acute and chronic rejection, and graft survival rates were found. No laparoscopic or open donor required blood transfusion, reoperation, or hospital readmission. One laparoscopic donor (9%) was converted to open nephrectomy. For laparoscopic vs open donors, median operative time was longer (difference, 67 min; P =.08), but median postoperative length of stay was significantly shorter (3 vs 5 days; P =.02)., Conclusions: Laparoscopic live donor nephrectomy has no adverse impact on pediatric recipient outcomes. For donors, the laparoscopic operation is safe and the hospital stay is shortened. These results support the continued use of laparoscopically procured live donor kidneys in pediatric renal transplantation.

Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring. The mean QTc interval in the CRF and post-Tx cohorts was normal at 407.9 ms and 408.2 ms, respectively. None of the children with CRF had QTc prolongation. Two Tx recipients had QTc prolongation; both had cardiac dilatation on echocardiography (ECHO). There was no correlation between the QTc interval and the creatinine clearance in either group. However, a significant correlation was noted between QTc prolongation and cardiac dilatation on ECHO in the Tx group (P=0.02, Fisher's exact test). In conclusion, QTc prolongation is uncommon in children with CRF and following Tx, in the absence of cardiac dilatation. However, caution is still needed before prescribing medications known to cause QTc prolongation.

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

A letter to the editor is presented in response to the article "Child and parental perspectives of multidimensional quality of life outcomes after kidney transplantation," by S.J. Anthony and colleagues in the 2010 issue.