Ureteral stricture after pediatric kidney transplantation: Is there a role for percutaneous antegrade ureteroplasty?

INTRODUCTION: Ureteral obstruction following pediatric kidney transplantation occurs in 5-8% of cases. We describe our experience with percutaneous antegrade ureteroplasty for the treatment of ureteral stricture in pediatric kidney transplant patients. METHODS: We retrospectively reviewed all pediatric kidney transplantation patients who presented with ureteral stricture and underwent percutaneous antegrade ureteroplasty at our institution from July 2009 to July 2021. Variables included patient demographics, timing of presentation, location and extent of stricture, ureteroplasty technique and clinical outcomes. Our primary outcome was persistent obstruction of the kidney transplant. RESULTS: Twelve patients met inclusion criteria (4.2% of all transplants). Median age at time of ureteroplasty was 11.5 years (range: 3-17.5 years). Median time from kidney transplantation to ureteroplasty was 3 months. Patency was maintained in 50% of patients. Seven patients (58.3%) required additional surgery. Four patients developed vesicoureteral reflux. Patients with persistent obstruction had a longer time from transplant to ureteroplasty compared to those who achieved patency (19.3 vs 1.3 months, p = 0.0163). Of those treated within 6 months after transplantation, two patients (25%) required surgery for persistent obstruction (p = 0.06). All patients treated >1 year after transplantation had persistent obstruction following ureteroplasty (p = 0.06). CONCLUSION: Percutaneous antegrade ureteroplasty can be considered a viable minimally invasive treatment option for pediatric patients who develop early ureteral obstruction (<6 months) following kidney transplantation. In patients who are successfully treated with ureteroplasty, 67% can develop vesicoureteral reflux into the transplant kidney. Patients who fail early percutaneous ureteroplasty or develop obstruction >1 year after transplantation are best managed with surgical intervention.

A new chapter in an evolving pandemic: Successful pediatric liver transplantation with SARS-CoV-2+ donors.

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors. METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform. RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a 16-month-old boy with cardiopulmonary arrest of unknown etiology. Three NAT tests (2 NP swab/1 BAL) prior to procurement failed to detect SARS-CoV-2. The diagnosis was made when the medical examiner repeated 2 NP swab NATs and an archive plasma NAT, all positive for SARS-CoV-2. Both 2-year-old recipients continue to do well 8 months post-transplant, with excellent graft function and no evidence of SARS-CoV-2 transmission. CONCLUSIONS: This is the first report to describe successful pediatric liver transplantation from SARS-CoV-2+ donors. These data reinforce the adult transplant experience and support the judicious use of SARS-CoV-2+ donors for liver transplantation in children. With SARS-CoV-2 becoming endemic, the concern for donor-derived viral transmission must now be weighed against the realized benefit of life-saving transplantation in the pediatric population as we continue to work toward donor pool maximization.

Good outcomes after pediatric intraperitoneal kidney transplant.

BACKGROUND: Kidney transplantation in small children is technically challenging. Consideration of whether to use intraperitoneal versus extraperitoneal placement of the graft depends on patient size, clinical history, anatomy, and surgical preference. We report a large single-center experience of intraperitoneal kidney transplantation and their outcomes. METHODS: We conducted a retrospective review of pediatric patients who underwent kidney transplantation from April 2011 to March 2018 at a single large volume center. We identified those with intraperitoneal placement and assessed their outcomes, including graft and patient survival, rejection episodes, and surgical or non-surgical complications. RESULTS: Forty-six of 168 pediatric kidney transplants (27%) were placed intraperitoneally in children mean age 5.5 ± 2.3 years (range 1.6-10 years) with median body weight 18.2 ± 5 kg (range 11.4-28.6 kg) during the study period. Two patients (4%) had vascular complications; 10 (22%) had urologic complications requiring intervention; all retained graft function. Thirteen patients (28%) had prolonged post-operative ileus. Eight (17%) patients had rejection episodes ≤6 months post-transplant. Only one case resulted in graft loss and was associated with recurrent focal segmental glomerular sclerosis (FSGS). Two patients (4%) had chronic rejection and subsequent graft loss by 5-year follow-up. At 7-year follow-up, graft survival was 93% and patient survival was 98%. CONCLUSIONS: The intraperitoneal approach offers access to the great vessels, which allows greater inflow and outflow and more abdominal capacity for an adult donor kidney, which is beneficial in very small patients. Risk of graft failure and surgical complications were not increased when compared to other published data on pediatric kidney transplants.

The impact of diabetes on young transplant recipients: An American perspective.

Despite advancements in diabetic care, diabetic kidney transplant recipients have significantly worse outcomes than non-diabetics. AIM: Our study aims to demonstrate the impact of diabetes, types I and II, on American young adults (18-40 years old) requiring kidney transplantation. METHODS: Using the United Network for Organ Sharing database, we conducted a population cohort study that included all first-time, kidney-only transplant recipients during 2002-2019, ages 18-40 years old. Patients were grouped according to indication for transplant. Primary outcomes were cumulative all-cause mortality and death-censored graft failure. Death-censored graft failure and patient survival at 1, 5, and 10 years were calculated via the Kaplan-Meier method. Multivariate Cox regression was used to assess for potential confounders. RESULTS: Of 42 466 transplant recipients, 3418 (8.1%) had end-stage kidney disease associated with diabetes. At each time-point, cumulative mortality was higher in diabetics compared to patients with non-diabetic causes of renal failure. Conversely, cumulative graft failure was similar between the groups. Adjusted hazard ratios for all-cause mortality and graft failure in diabetics were 2.99 (95% CI 2.67-3.35; p < .01) and 0.98 (95% CI 0.92-1.05, p < .01), respectively. CONCLUSION: Diabetes mellitus in young adult kidney transplant recipients is associated with a nearly three-fold increase in mortality, reflecting a relatively vulnerable patient population. Identifying the underlying causes of poor outcomes in this population should be a priority for future study.

Splenic Artery Transposition for Liver Transplantation: An Underutilized Technique?

BACKGROUND: Successful liver transplantation is dependent on restoration of hepatic arterial (HA) flow. Although uncommon, some native recipient HAs are not suitable or inadequate for anastomosis, thereby necessitating extra-anatomic HA reconstruction. Splenic artery transposition (SAT) is 1 method of HA reconstruction, in which the recipient splenic artery is transposed to reestablish perfusion of the donor liver. Due to the rarity of the technique, literature describing outcomes is limited. In the current report, we describe 3 patients (2 adults, 1 pediatric) who underwent complex upper abdominal surgery before whole-organ deceased donor liver transplantation with SAT. METHODS: The demographic and patient care information was collected prospectively and subsequently reviewed retrospectively. Given the de-identified nature of the data included, this study was exempt from approval from an ethics board. RESULTS: Recipient splenic arteries were dissected from their origin at the celiac trunk, for approximately 3-5 cm to ensure a gentle anterior-cranial curve toward the right upper quadrant, allowing anastomosis to the donor celiac trunk in an end-to-end fashion. Postoperatively, all 3 patients had rapid normalization of liver function tests and brisk HA flow demonstrated by Doppler ultrasound. Longer-term follow-up, ranging from 1 to 3 years, reveals continued patency of the reconstructed HAs and liver function tests within normal limits. CONCLUSIONS: Our experience points to SAT as a safe and effective technique for extra-anatomic HA reconstruction.

Pediatric discard risk index for predicting pediatric liver allograft discard.

BACKGROUND: Of the 600 pediatric candidates added to the liver waiting list annually, 100 will remain waiting while over 100 liver allografts are discarded, often for subjective reasons. METHODS: We created a risk index to predict discard to better optimize donor supply. We used the UNOS database to retrospectively analyze 17 367 deceased donors (≤18 years old) through univariate and multivariate logistic regression models. Deceased donor clinical characteristics and laboratory values were independent variables with discard being the dependent variable in the analysis. Significant univariate factors (P-value < .05) comprised the multivariate analysis. Significant variables from the multivariate analysis were incorporated into the pDSRI, producing a risk score for discard. RESULTS: From 17 potential factors, 11 were identified as significant predictors (P < .05) of pediatric liver allograft discard. The most significant risk factors were as follows: DCD; total bilirubin >10 mg/dL, and alanine transaminase (ALT) ≥500 IU/L. The pDSRI has a C-statistic of 0.846 for the training set and 0.840 for the validation set. CONCLUSION: The pDSRI uses 11 significant risk factors, including elevated liver function tests, donor demographics, and donor risk/type to accurately predict risk of pediatric liver allograft discard and serve as a tool that may maximize donor yield.

Liver transplant in a recently COVID-19 positive child with hepatoblastoma.

We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4-year-old male with COVID-19 prior to transplant. The first negative NP swab was documented 1 month after initial diagnosis, when SARS-CoV-2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL-4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for 4 weeks, he underwent a whole-organ pediatric liver transplant. COVID-19 positivity determined via NP swab SARS-CoV-2 real-time RT-PCR (Hologic Aptima SARS-CoV-2 RT-PCR assay). IgG and IgM total SARS- CoV-2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti-SARS-CoV-2 Test. Patient received standard prednisone and tacrolimus-based immunosuppression without induction therapy following transplant. Post-transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post-transplant day #11. Surveillance tests have remained negative with persistent SARS-CoV-2 IgG antibodies at 6 weeks after transplant. We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID-19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID-19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID-19.

The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series.

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Donor and transplant candidate selection for solid organ transplantation during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating donors and recipients with possible SARS-CoV-2 infection. Our current communication shares a protocol for donor and transplant recipient selection during the coronavirus disease 2019 (COVID-19) pandemic to continue lifesaving solid organ transplantation for heart, lung, liver, and kidney recipients. The initial results using this protocol are presented here and meant to encourage dialogue between providers, offering ideas to improve safety in solid organ transplantation with limited health care resources. This protocol was created utilizing the guidelines of various organizations and from the clinical experience of the authors and will continue to evolve as more is understood about SARS-CoV-2 and how it affects organ donors and transplant recipients.

A learning curve in using orphan liver allografts for transplantation.

Given the critical shortage of donor livers, marginal liver allografts have potential to increase donor supply. We investigate trends and long-term outcomes of liver transplant using national share allografts transplanted after rejection at the local and regional levels. We studied a cohort of 75 050 candidates listed in the Organ Procurement and Transplantation Network for liver transplantation between 2002 and 2016. We compared patients receiving national share and regional/local share allografts from 2002-2006, 2007-2011, and 2012-2016, performing multivariate Cox regression for graft survival. Recipient and center-level covariates that were not significant (P < .05) were removed. Graft survival of national share allografts improved over time. National share allografts had a 26% increased risk for graft failure in 2002-2006 but no impact on graft survival in 2007-2011 and 2012-2016. The cold ischemia time (CIT) of national share allografts decreased from 10.4 to 8.0 hours. We demonstrate that CIT had significant impact on graft survival using national share allografts (CIT <6 hours: hazard ratio 0.75 and CIT >12 hours: hazard ratio 1.25). Despite a trend toward sicker recipients and poorer quality allografts, graft survival outcomes using national share allografts have improved to benchmark levels. Reduction in cold ischemia time is a possible explanation.

The decreasing predictive power of MELD in an era of changing etiology of liver disease.

The field of liver transplantation has shifted considerably in the MELD era, including changing allocation, immunosuppression, and liver failure etiologies, as well as better supportive therapies. Our aim was to evaluate the predictive accuracy of the MELD score over time. The United Network for Organ Sharing provided de-identified data on 120 156 patients listed for liver transplant from 2002-2016. The ability of the MELD score to predict 90-day mortality was evaluated by a concordance (C-) statistic and corroborated with competing risk analysis. The MELD score's concordance with 90-day mortality has downtrended from 0.80 in 2003 to 0.70 in 2015. While lab MELD scores at listing and transplant climbed in that interval, score at waitlist death remained steady near 35. Listing age increased from 50 to 54 years. HCV-positive status at listing dropped from 33 to 17%. The concordance of MELD and mortality does not differ with age (>60 = 0.73, <60 = 0.74), but is lower in diseases that are increasing most rapidly-alcoholic liver disease and non-alcoholic fatty liver disease-and higher in those that are declining, particularly in HCV-positive patients (HCV positive = 0.77; negative = 0.73). While MELD still predicts mortality, its accuracy has decreased; changing etiology of disease may contribute.

Successful kidney transplantation in a small child with end-stage renal disease due to angiotensin receptor blocker fetopathy and atretic inferior vena cava.

Kidney transplantation is the treatment of choice in pediatric patients with end-stage renal disease. This population presents technical challenges particularly in those less than 20 kg due to anomalous anatomy, vascular access issues prior to transplantation, and a generally small size for age. Standard allograft outflow is usually achieved utilizing the iliac veins or IVC. When use of the iliocaval system is not feasible, alternative anastomosis must be considered. Herein, we report a case of a pediatric kidney transplantation where successful allograft outflow was achieved using the SMV when he was found to have an atretic IVC intraoperatively. In this setting, use of the portal system was required to achieve adequate allograft outflow. We created a donor iliac graft for added length to anastomose the renal vein with the SMV. In the setting of IVC occlusion with poor drainage, we utilized a patent vessel with larger caliber for outflow to reduce the risk of high venous pressures, allograft failure, venous rotation, and thrombosis. We conclude that the SMV may serve as an alternative outflow tract in the small pediatric patient and provides the vessel caliber needed to reduce the risks of complications.

Intraoperative blood loss and transfusion during primary pediatric liver transplantation: A single-center experience.

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

No Gains in Long-term Survival After Liver Transplantation Over the Past Three Decades.

OBJECTIVE: The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. SUMMARY OF BACKGROUND DATA: Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. METHODS: We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. RESULTS: There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001). CONCLUSION: In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

Reoperative complications following pediatric liver transplantation.

BACKGROUND: The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications. METHODS: All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30 days or the same hospital admission as the transplant operation, excluding retransplantation. RESULTS: Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p = 0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39 days vs. 11 days, p = 0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression. CONCLUSION: At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.