Pediatric deceased donor renal transplantation: An approach to decision making I. Pediatric kidney allocation in the USA: The old and the new

Renal transplantation is the treatment of choice for children with end‐stage renal disease. More than 50% of children receive a deceased donor renal transplant. Marked disparity between the number of children on the renal transplant wait list and the supply has prompted numerous advances to increase supply as well as maximize the utility of donor organs. Allocation of deceased donor kidneys is based on several criteria. The organ allocation system policy is continually evaluated and changed incrementally to optimize allocation. We, in the United Sates, are in the process of transitioning into a new kidney allocation system to enhance post‐transplant survival benefit, increase utilization of donated kidneys, and increase transplant access for biologically disadvantaged candidates. This review will provide a brief overview of the organ sharing system in the United States, compare the “old” and the “new” allocation system, and discuss the considerations for the pediatric nephrologist while accepting a deceased donor kidney for a particular pediatric patient.     

Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation

Olaitan OK, Zimmermann JA, Shields WP, Rodriguez-Navas G, Awan A, Mohan P, Little DM, Hickey DP. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.
Pediatr Transplantation 2010: 14: 87–92. © 2009 John Wiley & Sons A/S.
Abstract:  To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius^®. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.     

Cytokine concentrations and regulatory T cells in living donor and deceased donor liver transplant recipients

Outcomes of pediatric liver transplantation have constantly improved in the last decade. Living‐related liver transplantation does not seem to improve long‐term outcomes following liver transplantation, but few studies have evaluated immunological parameters of the alloimmune response after living vs. deceased donor organ transplantation. We analyzed numbers of regulatory T cells, lymphocyte subsets, and serum cytokine concentrations in 12 pediatric recipients of living‐related liver transplants and in 28 pediatric recipients of deceased donor organs during their annual follow‐ups. Transplant recipients who underwent living donor organ transplantation had significantly higher numbers of regulatory T cells and IL‐4 serum concentrations than recipients of deceased donor organs; both of these factors are associated with beneficial outcomes and transplantation tolerance. Living‐related liver transplantation may have potentially beneficial immunological aspects, although long‐term outcomes do not seem to be better in recipients of living donor organs than in recipients of deceased donor organs. Further studies are needed to compare immunological aspects of the two transplant procedures.     

Bilateral adrenal hemorrhage in a neonatal kidney donor

EKT from neonatal donors remains rare despite successful outcome being reported. The surgical aspects of neonatal abdominal organ recovery remain unfamiliar to the vast majority of abdominal organ recovery teams and renal transplant surgeons. BAH is not uncommon in newborn babies suffering distress in the perinatal period. BAH is often also associated with RVT and will impact on utilization of kidneys for transplantation. We present a case of a neonatal kidney donor with massive BAHs discovered at the time of organ recovery. This made the procurement challenging. Both kidneys were recovered en bloc with pancreas and the liver with aorta and inferior vena cave as vascular conduits. The kidneys were successfully implanted into an adult recipient with good function at 1‐year follow‐up. Association between adrenal hemorrhage and RVT needs to be considered before utilizing such kidneys. This case exemplifies successful outcome after careful assessment and transplantation of such kidneys.     

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.     

Impact of donor preprocurement cardiac arrest on clinical outcomes in pediatric deceased donor liver transplantation

PPCA has historically been considered detrimental to donor quality in LT, but transplantation of grafts from this group of donors is now routine. Our study aims to evaluate the outcomes associated with use of donors with a history of PPCA in the pediatric population. This study is a single‐center retrospective analysis of all pediatric LTs performed over an 18‐year period. Donors and recipients were stratified by the presence and length of donor PPCA time. Preprocurement donor and post‐transplant recipient laboratory values were collected to assess the degree of ischemic liver injury associated with each donor group. Cox regression analysis was used to compare survival. The records for 130 deceased pediatric LT donors and corresponding recipients were reviewed. There were 73 (56%) non‐PPCA donors and 57 (44%) PPCA donors. Donors that experienced a PPCA event demonstrated a higher median, pretransplant peak alanine aminotransferase (ALT) level (P < .001). When comparing post‐transplant recipient median ALT levels, donors with any PPCA had lower median peak ALT (P = .15) and day 3 ALT (P = .43) levels than the non‐PPCA group. Rates of early graft loss did not differ. The PPCA group with >40 minutes of ischemia had markedly lower survival at 10 years, but this finding did not reach statistical significance. Liver grafts from donors with or without PPCA demonstrated no statistically significant differences in function or survival. A history of donor PPCA alone should not be used as an exclusionary criterion in pediatric liver transplantation.     

Outcomes of pediatric living donor kidney transplantation: A single‐center experience

Renal transplantation is the treatment of choice for children with ESRD offering advantages of improved survival, growth potential, cognitive development, and quality of life. The aim of our study was to compare the outcomes of LDKT vs DDKT performed in children at a single center. Retrospective chart review of pediatric patients who underwent kidney transplantation from 2005 to 2014 was performed. Ninety‐one renal transplants were accomplished, and 31 cases (38.27%) were LDKT, and in 96.7% of the cases, the graft was obtained through laparoscopy. Thirty‐four receptors weighted <25 kg. LDKT group had statistically significant lower cold ischemia times than DDKT one. Complication rate was 9.67% for LDKT and 18.33% for DDKT. eGFR was better in LDKT. Patient survival rate was 100% for LDKT and 98.3% for DDKT, and graft survival rate was 96.7% for LDKT and 88.33%‐80% for DDKT at a year and 5 years. Our program of pediatric kidney transplantation has achieved optimal patient and graft survival rates with low rate of complications. Living donor pediatric kidney transplants have higher patient and better graft survival rates than deceased donor kidney transplants.     

Use of organs from increased infectious risk deceased donors in pediatric kidney transplantation

Living donors are the main source of transplanted kidneys for children and young people in many countries, but there still remains a significant need for deceased donor kidney transplantation. Given the waiting times associated with deceased donor kidney transplantation and the morbidity or mortality that can occur in those on the waiting list, it is essential that the utilization of kidneys from deceased donors is optimized. The use of organs from deceased donors at increased risk of transmitting human immunodeficiency virus, hepatitis B virus, or hepatitis C virus is relatively common in adults, but far less so in children. The risks and benefits of the use of kidneys from increased infectious risk donors (IIRD) are discussed. The variation of definitions of IIRD between countries is explored as is the need for pediatric nephrologists and transplant surgeons to have an understanding of the prevalence of viral diseases within the country in which they work. The role of screening tests such as nucleic acid tests is examined, along with the concept of residual risk. Finally, considerations in acquiring informed consent in the use of kidneys from IIRDs in children and young people are discussed.     

Long-term outcome of deceased donor renal transplantation in pediatric recipients: A single-center experience from a developing country

Kute VB, Trivedi HL, Vanikar AV, Shah PR, Gumber MR, Patel HV, Munjappa BC, Modi PR, Gera DN. Long‐term outcome of deceased donor renal transplantation in pediatric recipients: A single‐center experience from a developing country Abstract: RTx is best treatment for children with ESRD. Data scarcity on DDRTx outcome in children prompted us to review our experience. This study was undertaken to evaluate patient/graft survival, function vis‐a‐vis SCr, rejection episodes, and mortality in DDRTx performed in 37 children between 1998 and 2011. The most common recipient diseases leading to ESRD were congenital anomalies of kidney and urinary tract (48.6%) and chronic glomerulonephritis (18.9%). Mean recipient age was 13.8 ± 3.1 yr; 67.5% (n = 25) were men. Mean donor age was 38.8 ± 18.6 yr; 48.5% (n = 18) were men. Mean dialysis duration pre‐transplantation was 15.5 ± 3.5 months. All recipients received r‐ATG, and triple immunosuppression. Over a mean follow‐up of 3.93 ± 3.5 yr, patient and graft survival rates were 72.9% (n = 27) and 83.7% (n = 31), respectively, with a mean SCr of 1.1 mg/dL; 21.6% (n = 8) of patients had acute rejection episodes; 24.3% (n = 9) of patients had DGF. A total of 27% (n = 10) patients died, mainly owing to infections (n = 6) and cardiovascular disease (n = 3). DDRTx is a viable option for children and achieves acceptable graft function with patient/graft survival over long‐term follow‐up, encouraging use of this approach.     

Pediatric liver-kidney transplantation for hepatorenal fibrocystic disease from a living donor

The indications for and the timing of LT and/or KT for the patients with HRFCD are based on the severity of liver and kidney involvement. Most organs come from living donors, because the number of deceased donors is extremely low in Japan. Therefore, patients with HRFCD may need two organs from living donors. Four patients with HRFCD underwent living donor LT and KT from a single donor. The type of transplantation included combined LKT in one case, sequential LKT in two cases, and sequential KLT in one case. Although the case of combined LKT died because of sepsis, the other cases were doing well. Sequential LKT was successfully performed at the proper timing for each transplant; however, both of the donors suffered from a gastroduodenal ulcer after liver donation because of the psychological burden related to the relatively short period between two donations. In conclusion, living donation for LKT with cautious surgical procedures is not harmful for donors and recipients. However, changes in the allocation system established for deceased donors for HRFCD should be considered to avoid the need for two organ donations from the same living donor.     

International Pediatric Transplant Association (IPTA) position statement supporting prioritizing pediatric recipients for deceased donor organ allocation

A position statement of the International Pediatric Transplant Association endorsing prioritizing pediatric recipients for deceased donor organ allocation, examining the key ethical arguments that serve as the foundation for that position, and making specific policy recommendations to support prioritizing pediatric recipients for deceased donor organ allocation globally.     

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.     

Trends in pediatric liver transplant donors and deceased donor circumstance of death in the United States, 2002‐2015

While much of the discussion regarding expanding the donor pool for pediatric liver transplantation has surrounded the use of technical variant grafts, little attention has been directed toward changes in the deceased donor population. The aim of this study was to investigate trends in the circumstance of the death of deceased donors used for pediatric liver transplantation. All pediatric liver transplant recipients transplanted between 2002 and 2015 were identified in the UNOS database and were categorized based on the donor circumstance of death. There was no significant correlation between year of transplantation and number of pediatric liver transplants performed, pediatric donors, split livers, or living donors. There was a significant downward trend in donors from motor vehicle fatalities and an upward trend in suicide, non‐MVA, and death due to natural causes. There was also an upward trend in drowning, one of the most common mechanisms of death among non‐MVA in 2015. While the number of donors who died in MVA has fallen, the number of deceased donors who died from suicide, natural causes, and non‐MVA, especially drowning, has increased, maintaining the overall number of pediatric deceased donor livers transplanted.     

Variability in donor selection among pediatric heart transplant providers: Results from an international survey

There is considerable variability in donor acceptance practices among adult heart transplant providers; however, pediatric data are lacking. The aim of this study was to assess donor acceptance practices among pediatric heart transplant professionals. The authors generated a survey to investigate clinicians’ donor acceptance practices. This survey was distributed to all members of the ISHLT Pediatric Council in April 2018. A total of 130 providers responded from 17 different countries. There was a wide range of acceptable criteria for potential donors. These included optimal donor‐to‐recipient weight ratio (lower limit: 50%‐150%, upper limit: 120%‐350%), maximum donor age (25‐75 years), and minimum acceptable left ventricular EF (30%‐60%). Non‐US centers demonstrated less restrictive donor selection criteria and were willing to accept older donors (50 vs 35 years, P < 0.001), greater size discrepancy (upper limit weight ratio 250% vs 200%, P = 0.009), and donors with a lower EF (45% vs 50%, P < 0.001). Recipient factors were most influential in the decision to accept marginal donors including recipients requiring ECMO support, ventilator support, and highly sensitized patients with a negative XM. However, programmatic factors impacted the decision to decline marginal donors including recent programmatic mortalities and concerns for programmatic restrictions from regulatory bodies. There is significant variation in donor acceptance practices among pediatric heart transplant professionals. Standardization of donor acceptance practices through the development of a consensus statement may help to improve donor utilization and reduce waitlist mortality.     

Pediatrics and donor‐derived disease transmission: The US OPTN experience

PDDTE are tracked by the OPTN Ad Hoc DTAC. Specific evaluation of potential transmissions from pediatric deceased donors or the impact of donor‐derived disease transmissions to pediatric organ recipients has not been previously undertaken. PDDTE reported to the DTAC between 2008 and 2013 were reviewed, characterized as proven, probable, possible, IWDT, unlikely, or excluded for both the whole event and each individual recipient. Pediatric donors and recipients were defined as being 0‐17 years of age. Analysis was undertaken to characterize potential disease transmission from pediatric donors to adult or pediatric recipients and also to evaluate potential transmission from all donors to pediatric recipients. P/P cases were further analyzed. A total of 5238 pediatric deceased US donors accounted for 17 456 organ transplants during the study period; 103 PDDTE reports arose from these donors (2.0%). PDDTE were characterized as P/P (15%), possible (13%), IWDT (9%), unlikely, and excluded (63%). Disease was transmitted to 22 of 54 potentially exposed (adult and pediatric) recipients with six attributable deaths. An infectious pathogen accounted for 13/15 of the P/P PDDTE associated with pediatric donors, affecting 19 of 50 potentially exposed recipients and resulting in five deaths. Four separate viral pathogens from six donors accounted for P/P transmissions to 11 recipients with the unanticipated transmission of CMV most common. No pediatric donor transmitted HIV, HBV, or HCV. Bacteria, fungi, and parasites accounted for three (all staphylococci), three (Zygomycetes and Histoplasma), and two (both Toxoplasma) P/P transmissions from seven donors, respectively. From the recipient side, 11/11,188 pediatric recipient deceased and living donor transplants during the study period were associated with a P/P PDDTE (<0.1%) with infectious pathogens accounting for 9/11 P/P events. Infections were split among pathogen categories (bacteria 2, viruses 3, parasites 3, and fungi 1). Reporting rates of PDDTE involving pediatric donors were very low and similar to rates from all donors, with resulting P/P transmissions occurring in only 0.1% of exposed recipients, but transmissions were associated with six deaths. Rates of P/P transmission to pediatric recipients from any donor (<0.1%) were also very low and similar to that of all recipients. Additional studies are needed to compare the pattern and outcome of donor‐derived disease transmission from and to pediatric and adult donor and recipients.     

Review of the impact of donor characteristics on pediatric heart transplant outcomes

Heart transplantation (HTx) is a treatment option for end‐stage heart failure in children. HTx is limited by the availability and acceptability of donor hearts. Refusal of donor hearts has been reported to be common with reasons for refusal including preexisting donor characteristics. This review will focus on the impact of donor characteristics and comorbidities on outcomes following pediatric HTx. A literature review was performed to identify articles on donor characteristics and comorbidities and pediatric HTx outcomes. There are many donor characteristics to consider when accepting a donor heart. Weight‐based matching is the most common form of matching in pediatric HTx with a donor‐recipient weight ratio between 0.7 and 3 having limited impact on outcomes. From an age perspective, donors <50 years can be carefully considered, but the impact of ischemic time needs to be understood. To increase the donor pool, with minimal impact on outcomes, ABO‐incompatible donors should be considered in patients that are eligible. Other factors to be considered when accepting an organ is donor comorbidities. Little is known about donor comorbidities in pediatric HTx, with most of the data available focusing on infections. Being aware of the potential infections in the donor, understanding the testing available and risks of transmission, and treatment options for the recipient is essential. There are a number of donor characteristics that potentially impact outcomes following pediatric HTx, but these need to be taken into consideration along with their interactions with recipient factors when interpreting the outcomes following HTx.     

Liver transplantation from a deceased donor with β‐thalassemia intermedia is not contraindicated: A case report

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β‐thalassemia intermedia. A patient, 6‐year‐old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron‐related organ toxicity and transplant failure. Follow‐up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure.     

Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living‐donor–dominant program

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.     

Laparoscopic live donor nephrectomy: the pediatric recipient in a dual-site program

BACKGROUND: At our institution, laparoscopic live donor nephrectomy (LLDN) is done at a different hospital site than pediatric recipient transplantation, whereas open donor nephrectomy (OLDN) is done in the adjacent operating room. The purpose of this study was to evaluate the safety of a dual-site renal transplantation program by comparing the outcomes of pediatric recipients of LLDN vs. OLDN. METHODS: This is a retrospective study of consecutive pediatric recipients (n = 10) of LLDN (June 2002 to June 2005) compared to the 10 most recent pediatric recipients of OLDN (March 2001 to June 2005). Renal function was assessed with calculated creatinine clearance using the Schwartz formula and the following outcomes were assessed: delayed graft function, ureteral complications, acute rejection and patient and graft survival. Results are expressed as median (IQR). RESULTS: When comparing the laparoscopic vs. open group, there were no significant differences in recipient age, height, weight, preoperative calculated creatinine clearance and warm ischemia time. Twelve month postoperative creatinine clearance was 88 ml/min/1.73 m(2) (57-99) in the laparoscopic group (n = 8) and 66 ml/min/1.73 m(2) (60-86) in the open group (n = 9), p = 0.2. In the LLDN group vs. the OLDN group, delayed graft function was 0% vs. 10% (p = 1.0), ureteral complications were 20% vs. 30% (p = 1.0), and acute rejection was 20% vs. 40% (p = 0.6). In the laparoscopic group, one-yr patient and graft survival were both 100%, as compared to 100% and 89%, respectively, in the open group. CONCLUSION: A dual-site laparoscopic donor nephrectomy program is not associated with adverse pediatric recipient outcomes when compared to a same-site open donor approach.     

Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis

Abstract:  Sensitization following renal transplant is a significant barrier to repeat transplantation in children. We report a successful DD renal transplant, with the use of PP, in an 11-yr-old girl who became highly sensitized following a prior failed transplant. She received PP treatments after failure of high-dose IVIg (Gamimune^®). We established the effectiveness of PP by attaining a 0% PRA and negative cross-matches after five PP treatments. Subsequently, our patient underwent a second round of scheduled PP. When the PRA was 0%, unacceptable antigens were removed from the UNOS wait list, PP was continued, and a kidney became available within 10 days. The final flow cytometry cross-match with the eventual donor was negative. This success demonstrates that coordination of desensitization by PP and advanced laboratory monitoring techniques with recent policies regarding allocation of organs to pediatric patients provides new opportunities for children awaiting transplantation. Since the transplant, our patient sustained a low-titer increase of anti-HLA antibodies. However, she has had no episodes of acute rejection and has maintained excellent graft function more than 17 months later.