Impact of center volume and the adoption of laparoscopic donor nephrectomy on outcomes in pediatric kidney transplantation

Reports for pediatric kidney transplant recipients suggested better outcomes for ODN compared to LDN. Contemporary outcomes stratified by donor type and center volume have not been evaluated in a national dataset. UNOS data (2000‐2014) were analyzed for pediatric living donor kidney transplant recipients. The primary outcome was GF; secondary outcomes were DGF, rejection, and patient survival. Live donor nephrectomies for pediatric recipients decreased 30% and transitioned from ODN to LDN. GF rates did not differ for ODN vs LDN (P = .24). GF was lowest at high volume centers (P < .01). Donor operative approach did not contribute to GF. LDN was associated with less rejection than ODN (OR 0.66, CI 0.5‐0.87, P < .01). Analysis of the 0‐ to 5‐yr recipient group showed no effect of ODN vs LDN on GF or rejection. For the contemporary era, there was no association between DGF and LDN in the 0‐ to 5‐yr group (OR 1.12, CI 0.67‐1.89, P = .67). Outcomes of kidney transplants in pediatric recipients following LDN have improved since its introduction and LDN should be the approach for live donor nephrectomy regardless of recipient age. The association between case volume and improved outcomes highlights future challenges in organ transplantation.     

Lymphocyte‐depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients

The use of lymphocyte‐depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high‐risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first‐time pediatric KT recipients using SRTR data (2000‐2014). Characteristics were compared across race using Wilcoxon rank‐sum tests for continuous and chi‐square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte‐depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52‐0.83 P < .001) compared to AA recipients receiving anti‐IL‐2 receptor antibody induction. This difference was not seen in non‐AA recipients receiving lymphocyte‐depleting induction (RR, 0.93; 95% CI, 0.81‐1.06, P = .26) compared to IL‐2 induction. These findings support a role for lymphocyte‐depleting induction agents in AA pediatric patients undergoing KT and continued use of IL‐2 inhibitor induction in non‐AA pediatric KT recipients.     

Outcomes of children receiving en bloc renal transplants from small pediatric donors

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 m². 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.     

Donation after cardiac death kidneys are suitable for pediatric recipients

Despite the high number of children listed for kidney transplantation and shortage of deceased organ donors, there is reluctance to utilize DCD kidneys in pediatric recipients. We examined outcomes in pediatric kidney transplant patients who received a DCD kidney allograft. UNOS database was queried to examine outcomes in all pediatric kidney transplant recipients from 1994 to 2017. Pediatric status was defined as <18 years at the time of transplantation. Recipients were divided by DBD or DCD allograft status. Donor and recipient demographic data were examined. Patient and allograft survival was calculated, and Kaplan‐Meier survival curves were generated. A P‐value of <0.05 was considered to be significant. A total of 286 pediatric kidney transplant recipients received a DCD allograft. The donors in the DCD group were significantly younger than those in the DBD group (21.7 vs 23.3 years), with a higher KDPI (26.5% vs 22.9%). In the DCD group, the average age at transplant was younger (11.6 vs 12.9 years), with no difference in cold ischemia time or length of stay between the two groups. Rates of delayed graft function were higher in the DCD group, but despite this, there were no significant differences in allograft or patient survival between the groups. There is no difference in allograft survival in pediatric kidney transplant recipients who receive a DCD kidney allograft. DCD kidney allografts are suitable for transplantation in pediatric patients and can greatly expand the donor pool.     

Very small pediatric donor kidney transplantation in pediatric recipients

Kidneys from very small pediatric donors (age <5 years, weight <21 kg) may be a means to increase the donor pool for pediatric recipients. Transplantation of small pediatric kidneys is more commonly performed in adult recipients due to the increased risks of technical complications, thrombosis, and early graft failure. While these risks are abrogated in adult recipients by limiting the donor weight to ≥10 kg and using the EB technique, it is unknown whether pediatric recipients achieve comparable results. US national data were assessed for all first‐time, deceased‐donor, kidney‐only pediatric recipients, 1/1996‐10/2013, who received very small pediatric donor grafts or grafts from ideal adult donors. We identified 57 pediatric EB, 110 pediatric SK, and 2350 adult transplants. The primary outcome was 3‐year all‐cause graft survival. Kaplan‐Meier curves showed worse outcomes for pediatric grafts compared to adult ideal grafts (P=.042). On multivariate analysis, pediatric recipients of SK grafts had significantly higher HRs (aHR 2.01, 95% CI 1.34‐3.00) and pediatric recipients of EB grafts had somewhat higher non‐significant HRs (1.57; 95% CI 0.88‐2.79) for graft survival. These results suggest cautionary use of very small pediatric donors as a source to expand the donor pool for pediatric candidates.     

Kidney transplantation from pediatric donors: size-match-based allocation

Abstract:  Use of kidneys from pediatric donors has been associated with worse outcome. We review our 20-yr experience using pediatric kidneys as single grafts in children and adult recipients. Charts review of 29 recipients, transplanted between 1986 and 2005, who received a graft from a donor ≤6 yr was performed. One recipient received "en bloc" graft and the remaining patients received a single kidney. Nine recipients were adults and 21 were children. Creatinine at discharge and at follow-up was recorded and actuarial graft and patient survivals were calculated using life table analysis. All 29 recipients are alive at mean follow-up of 92 months. Five grafts were lost for: primary non-function (1), recurrent FSGS at 14 month (1) and chronic rejection (3). All five recipients who lost their graft received a graft from donors ≤3 yr. Mean calculated GFR (Schwartz formula) at one and five yr were 84.2 mL/m²/1.73 and 98.3 mL/m²/1.73, respectively. Actuarial graft survival was 93.2%, 89.6%, and 81.9% at one, five and at 10 yr after transplant. The use of a single kidney graft from pediatric donors yields good long-term results. Kidneys from small pediatric donors should be allocated first to matched-weight recipients but otherwise can be transplanted in older children or in adults.     

Bortezomib in the treatment of antibody‐mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study

Antibody‐mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody‐mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy‐proven antibody‐mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty‐three patients received bortezomib for antibody‐mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow‐up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post‐bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty‐six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune‐dominant donor‐specific antibody, 1‐3 months after the first dose of bortezomib. Non‐life‐threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life‐threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3‐6 months in pediatric kidney transplant recipients with antibody‐mediated rejection.     

Role of race in kidney transplant outcomes in children with focal segmental glomerulosclerosis

It is well established that racial differences exist in kidney transplant outcomes; however, there are no studies which focus on the role of race in transplant outcomes specifically in children diagnosed with FSGS. Associations between race and transplant outcomes in FSGS children were evaluated using the Organ Procurement and Transplantation Network database from 2000 to 2012. Recipients aged 2–21 years who received a kidney‐only transplant were included. Multivariate regression models were used to evaluate transplant outcomes by race. Five hundred and thirty‐six recipients (59.7% male, 15.6±3.9 years) were black and 1134 (55.7% male, 14.3±5.0 years) were non‐black. Graft survival was significantly shorter in the black group (4.2±3.1 vs 4.6±3.3 years, P=.005). Black race was associated with significantly higher risk of graft failure (HR 1.34, 95% CI=1.21–1.49, P<.0001), acute rejection (OR 1.66 95% CI=1.39–1.97, P<.0001), and delayed graft function (OR 1.51, 95% CI=1.33–1.72, P<.001) compared to non‐black race. There were no significant differences in mortality, prolonged hospitalization, or FSGS recurrence between groups. Race is a significant predictor for worse transplant outcomes in children with FSGS.     

The impact of public health service increased risk donors in pediatric liver transplantation

Many transplant programs are reluctant to use organs from deceased donors designated as “PHS increased risk” due to misconceptions regarding the quality of those organs. This study evaluated the impact of PHS increased risk donors on patient and allograft survival in pediatric patients undergoing liver transplantation. Retrospective analysis of the UNOS database from January 2005 through September 2017 revealed 5615 pediatric patients who underwent isolated liver transplantation; of these, 5057 patients received primary isolated liver transplants and 558 patients received isolated liver retransplants. PHS increased risk organs were used in 6.7% and 5.4% of the children receiving primary isolated and retransplant livers, respectively. Cox proportional hazards models adjusted for donor and recipient characteristics determined the relative risk of PHS status on allograft and patient survival. Sicker children (those in ICU [P < .001] and on life support [P = .04]) were more likely to receive PHS increased risk donor organs. There were no differences in overall patient (P = .61) or allograft (P = .68) survival between pediatric patients receiving PHS positive vs PHS negative deceased donor organs; adjusted models also demonstrated no statistically significant differences in patient or allograft survival. Excellent patient and allograft survival can be accomplished with PHS increased risk organs.     

Use of oral immunoglobulins to treat diarrhea in pediatric kidney transplant recipients—Single‐center experience and review of the literature

Effective treatment modalities for diarrhea in solid organ transplant recipients are lacking. We evaluated the effect of oral IgG on clinical course of diarrhea in pediatric kidney transplant recipients. We retrospectively studied all pediatric kidney transplant recipients who required hospitalization for diarrhea between January 1, 2015, and December 31, 2017. We divided the recipients into two groups based on whether they had received oral IgG to treat diarrhea. Sixteen pediatric kidney transplant recipients required hospitalization for diarrhea over 3 years. Median age at admission was 9.25 years (IQR:12.54). Fifty‐six percent of recipients were male, and 81% were white. Four patients received oral IgG for prolonged diarrhea. Oral IgG recipients had longer diarrheal duration before admission (median (days) 14.5 vs1; P .02), a trend for greater weight loss at admission (median (kilogram) 1.4 vs 0.2; P .3), and a trend for higher acute kidney injury (>75% reduction in glomerular filtration rate: 100% vs 42%; P .36). Diarrhea resolved completely in 3 (75%) oral IgG recipients and 7 (58%) non‐oral IgG patients by discharge (P .99). One oral IgG recipient showed partial improvement but also had biopsy evidence of mycophenolate‐induced colitis. All patients tolerated oral IgG well. No patients required re‐hospitalization within 30 days of discharge. Oral IgG may be used safely and effectively to treat prolonged diarrhea in pediatric kidney transplant recipients. A larger, randomized, prospective study is needed to further assess the efficacy of oral IgG in the treatment of diarrhea.     

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.     

Donor‐to‐recipient weight ratio is a risk factor for hepatic artery thrombosis after whole‐liver transplantation in children under 25 kg

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased‐donor liver transplantation from August 2002 to July 2016. Multi‐organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased‐donor liver transplant patients with a median age of 1.7 years (IQR 0.67‐6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole‐liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split‐liver graft recipients. Within the whole‐liver recipient group under 25 kg, 11 patients developed HAT with a median donor‐to‐recipient ratio (DRWR) of 0.9 (IQR: 0.7‐1.2) compared with a median DRWR of 1.4 (IQR: 1.1‐1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split‐liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.     

Satisfactory usage of kidneys from pediatric donors with severe hand foot mouth disease

No studies have reported making use of kidneys from pediatric donors with severe HFMD. Here, we retrospectively analyzed the feasibility and clinical effect of six cases of kidney transplantation from four pediatric donors with severe HFMD in our center between January 2014 and December 2016. The donors’ age ranged from 6 months to 3 years and 11 months. The recipients’ age ranged from 18 to 41 years. Single kidney transplantation was performed in four recipients, and dual splitting kidney transplantation and en bloc kidney transplantation were performed in two recipients, respectively. During the 1.5‐4 years follow‐up, all recipients maintained normal kidney allograft function except for one recipient whose allograft was removed due to the allograft artery thrombosis. The survival rates of recipient and allograft were 100% and 83.3%, respectively. None of the six recipients showed any symptoms associated with HFMD. In conclusion, it is feasible to perform kidney transplantation from pediatric donors with severe HFMD to adult recipients with immunity to the pathogens. The clinical effect is satisfactory.     

Barriers to live donor kidney transplants in the pediatric population: A single‐center experience

A decrease in live donor pediatric kidney transplants has occurred in the United States. This study investigates barriers that may influence access to live donor kidney transplants in children. Retrospective chart review was conducted for 91 children (69% male, mean age 11.9 years) who underwent pretransplant workup from 2005 to 2015 at an urban pediatric hospital. Fifty‐four percent were African American, 32% Caucasian, 8% Arabic, 3% Hispanic, and 3% Others. Government‐sponsored insurance (Medicaid/Medicare) was utilized by 73%, and 54% had dual caregivers. Only nine of 68 kidney transplants were live donor transplants. Live donor transplants (11%) were significantly (P=.008) lower than deceased donor transplants (59%) in African Americans. Private insurance was reported by 56% of live donor recipients and 25% of deceased donor recipients. Among live donor recipients, 78% were from dual caregiver families. Caregiver, health‐related, financial, and religious/cultural barriers to live donor transplants were reported, several of which may be amenable to positive intervention.     

Effects of the influenza vaccine on pediatric kidney transplant outcomes

The influenza vaccine is critical for preventing influenza‐related complications in transplant patients. Previous studies demonstrated de novo donor‐specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single‐center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post‐transplant. Using log‐rank tests and Kaplan‐Meier curves, vaccinated patients had a significantly lower risk of mortality (P = 0.048). There were no differences in death‐censored graft survival (P = 0.253), graft survival (P = 0.098), or rejection (P = 0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post‐transplant vaccination status considered as a time‐dependent covariate; analyses were performed using both a 360‐ and 180‐day vaccination period following any post‐transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P = 0.91), death‐censored graft survival (HR 0.70 [0.31, 1.58], P = 0.39), graft survival (HR 0.69 [0.32, 1.49], P = 0.34), or rejection (HR 0.67 [0.37, 1.19], P = 0.17). Eight patients developed de novo donor‐specific antibodies following the first post‐transplant influenza vaccination; three then developed biopsy‐proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.     

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.     

Non‐invasive staging of chronic kidney allograft damage using urine metabolomic profiling

Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS‐DA. We used mixed‐effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post‐transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85‐0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71‐0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non‐invasive assessment of histopathological damage.     

Varicella infection following vaccination in a pediatric kidney transplant recipient

Live viral vaccines have historically been avoided in children after solid organ transplantation. Multiple reports of safety and immunogenicity, largely in the pediatric liver transplant population, have led to a reconsideration of this recommendation. Here, we report the case of a 4‐year‐old boy who inadvertently received the live attenuated MMR‐varicella vaccine (MMRV) at a routine well‐child visit 16 months after receiving a living donor kidney transplant. This was not known until after he was admitted with rash and documented disseminated varicella infection 5 weeks later. He was treated with intravenous acyclovir followed by oral therapy and recovered fully. This case and its discussion illustrate what is still unknown about the risk‐to‐benefit ratio of live viral vaccination in any individual transplant recipient. Criteria to determine which patients should receive these vaccines should be evaluated before their use after transplant becomes routine, and all recipients and their families should be counseled to have a low threshold to seek medical care for any febrile illness or rash after live viral vaccination.     

Physical activity and its correlates in a pediatric solid‐organ transplant population

PA has been shown to have benefits in SOT patients. Studies assessing physical activity levels and its correlates in a pediatric solid‐organ transplant population are limited. The aim of this study was to assess PA levels and identify baseline and contemporaneous factors that contribute to PA in a pediatric SOT population. A retrospective cross‐sectional review was performed on 58 pediatric transplant patients (16 heart, 29 kidney, and 13 liver transplant). PA was measured by PAQ‐C or PAQ‐A. Demographics, baseline, and contemporaneous factors were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.2 [12.3‐17.3] years old at time of completing the PAQ. Median PAQ score was 2.2 [1.7‐2.9]. There were no significant differences in PAQ scores between organ transplant type or between genders. Lower PAQ score was associated with sensory disability (9 vs 49 without disability; P = <.01) and age at time of completing the PAQ (r = ?.50, P = <.01). These results suggest that older age at time of completing the PAQ and presence of sensory disability may influence PA levels in the pediatric SOT population.     

Donor‐specific antibodies in a pediatric kidney transplant population—Prevalence and association with antiproliferative drug dosing

Prevalence and implications of anti‐HLA class I and class II antibodies are beginning to be better characterized in pediatric kidney transplant recipients. dnDSA formation is predictive of AMR and downstream diminished graft function and survival. However, risk factors for the development of dnDSA are not well defined in this patient population. After introducing DSA surveillance into our pediatric kidney transplant program, we are reporting the prevalence of class I and class II DSA in 67 otherwise stable recipients. Secondary end‐points included risk factors for DSA development and assessment of graft function. Significantly, lower median daily MMF doses were observed in patients with DSAs compared to patients without DSAs (371 vs 617 mg/m²/d, respectively; P = 0.035). Class II DSA formation was more common, with a prevalence of 17.9%, as compared to 10.4% for class I DSA. Estimated glomerular filtration rate was also decreased in patients with positive DSA vs those with negative titers (71, SD 25 vs 78, SD 29 mL/min/1.73 m², respectively; P = 0.034). We conclude that reduced‐dose MMF is associated with dnDSA and DSA is associated with diminished graft function in stable pediatric kidney transplant recipients.