Eight‐year follow‐up in pediatric living donor kidney recipients receiving alemtuzumab induction

Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor‐specific acceptance. This was a single‐center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months—18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12‐29 days prior to transplantation, and the second at the time of transplantation. Maintenance IS was based on combination of low‐dose CNI and mycophenolate, with steroids tapered over the first 5 days post‐transplantation. Patients were followed for 7.8±1.3 years, and protocol biopsies were taken 1 month, 1, 3, and 5 years post‐transplant. The Kaplan‐Meier 8‐year patient and graft survival rates in the cyclosporine‐treated patients were 82.0±7.3% and 71.6±7.3, and in the tacrolimus‐treated patients were 97.2±5.4 and 83.8±6.0%. Biopsy‐proven acute rejection developed in 35% of cyclosporine‐treated patients and in 8% of tacrolimus‐treated patients. Alemtuzumab pretreatment prior to LRD kidney transplantation, followed by maintenance immunosuppression with tacrolimus and MMF, is associated with reasonable long‐term results in pediatric patients.     

Long‐term outcomes of pediatric living donor liver transplantation at a single institution

Oh SH, Kim KM, Kim DY, Lee YJ, Rhee KW, Jang JY, Chang SH, Lee SY, Kim J‐S, Choi BH, Park S‐J, Yoon CH, Ko G‐Y, Sung K‐B, Hwang G‐S, Choi K‐T, Yu E, Song G‐W, Ha T‐Y, Moon D‐B, Ahn C‐S, Kim K‐H, Hwang S, Park K‐M, Lee Y‐J, Lee S‐G. Long‐term outcomes of pediatric living donor liver transplantation at a single institution.
Pediatr Transplantation 2010: 14:870–878. © 2010 John Wiley & Sons A/S. Abstract: There have only been a few studies on the long‐term outcomes and prognostic factors after pediatric LDLT. We conducted a retrospective, single‐center assessment of the outcomes as well as the demographic and clinical factors that influenced the poor outcomes in 113 children aged <16 (median age 21 months; 6 months–15.5 yr) who underwent 115 LDLTs, predominantly for biliary atresia (60.9%) and FHF (14.8%), between 1994 and 2006 at Asan Medical Center. Left lateral segment or left lobe grafts were implanted into most of these children (86.9%) according to routine procedures. The overall rates of graft survival at one, five, and 10 yr were 89.6%, 83.0%, and 81.5%, respectively, and the overall rates of patient survival were 92.9%, 86.3%, and 84.8%, respectively. Virus‐related disease (41.2%) and chronic rejection (29.4%) were the major causes of mortality. On multivariate analysis, UNOS status 1a and 1b and chronic rejection were significant risk factors for both graft and patient loss, whereas the PELD score >25 was a significant risk factor for graft loss. Patient and graft survival may be related not only to post‐operative complications, but also to the patient’s preoperative clinical condition.     

Long‐term outcomes and predictors in pediatric liver retransplantation

Historically, 9–29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan–Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had “early” (≤30 days after primary transplant) and “late” retransplants. Eighty‐four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five‐yr follow‐up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long‐term immunosuppressant morbidity remains an opportunity for improvement.     

Hand-assisted laparoscopic donor nephrectomy for pediatric kidney allograft recipients

Laparoscopic donor nephrectomy (LDN) is the method of choice for procuring kidneys from living donors at many transplant centers. The aim of this study was to assess the feasibility as well as outcome of LDN in pediatric recipients. Twenty-two pediatric patients, 18-yr old or younger received kidneys procured by a hand-assisted LDN technique. The mean operative time was no different (p = 0.9) and the mean length of stay was more than 1 day shorter in the LDN group (p = 0.0001) compared with the 13 pediatric patients who received kidneys by standard open nephrectomy. Body mass index (BMI), number of donor kidney vessels, or laterality of the kidney did not impact the donor operation or outcome. Actuarial 1-yr patient survival was 100% and allograft survival was 95%, which are equivalent to registry data. There were no donor mortalities and there were five morbidities. None required hospitalization. There were no conversions from LDN to open nephrectomy. One kidney was lost because of overwhelming infection necessitating withdrawal of immunosuppression. In conclusion, hand-assisted LDN is a safe method of procuring kidneys from potential donors with no significant negative outcomes to the pediatric recipients.     

Impact of laparoscopic donor nephrectomy on allograft function in pediatric renal transplant recipients: a single-center report

Laparoscopic donor nephrectomy (LDN) is rapidly becoming the preferred technique for the procurement of living donor kidneys. An association of this technique with delayed graft function and higher risk for rejection has been reported in pediatric recipients. We reviewed our experience of 17 pediatric patients who received a living donor kidney, from 2002 to 2004, procured by LDN, and compared it with a matched group that received living donor kidneys harvested by the open technique. Patient demographics, etiology of renal failure, intra-operative events, length of stay, serum creatinine decline, and graft function were reviewed. Our experience confirmed the findings of earlier reports specifically in small pediatric recipients. The LDN group showed a significantly slower decline in creatinine in the immediate post-operative period and longer intra-operative time. However, there was no difference between the two groups in the length of hospital stay, and creatinine clearances at discharge, six, 12 and 24 months post-operatively. The incidence of acute rejection was similar in both groups. LDN is a safe procurement modality for pediatric patients. The risk for prolonged OR time and delay graft function has to be considered during the evaluation process.     

Comparison of outcomes of hand‐assisted laparoscopic to open donor nephrectomy for pediatric recipients

The purpose of this study is to compare the outcome of pediatric recipients of kidneys procured using a hand‐assisted laparoscopic (HALDN group) to an open technique (ODN group). Twenty‐eight patients ≤18 yr old (HALDN group) were compared with 17 patients (ODN group). The serum creatinine for HALDN and ODN groups at discharge were 0.93 ± 0.48 and 0.94 ± 0.54 mg/dL (p = 0.917), respectively. The serum creatinine for HALDN and ODN groups at six and 12 months was 1.01 ± 0.44 and 1.11 ± 0.55, and 1.04 ± 0.52 and 1.14 ± 0.46 mg/dL (p = 0.516, p = 0.554), respectively. The eGFR for HALDN and ODN groups at discharge was 108.66 ± 37.23 and 106.1 ± 50.55 mL/min/1.73 m² (p = 0.845), respectively. The eGFR for HALDN and ODN groups at six and 12 months was 97.77 ± 28.25 and 81.73 ± 27.46, and 94.56 ± 28.3 and 85.74 ± 30.1 mL/min/1.73 m2 (p = 0.085, p = 0.344), respectively. The patient and graft survival for both groups were 100% at 12 months post‐transplant. In conclusion, the short‐term outcome of recipients of kidneys procured via HALDN is comparable to that of kidneys procured via ODN in pediatric patients.     

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.     

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.     

Long‐term outcomes of simultaneous heart and kidney transplantation in pediatric recipients

Pediatric sHKTx has become an effective therapy for patients with combined cardiac and renal failure. Often, these patients develop human leukocyte antigen antibodies from their previous allografts and are therefore more difficult to re‐transplant. We describe the largest case series of a predominantly sensitized pediatric sHKTx with emphasis on medical management and patient outcomes. Demographics, clinical characteristics, antibody, and biopsy data were retrospectively collected from University of California, Los Angeles database and correlated with short‐ and long‐term patient and allograft outcomes of all sHKTx performed between 2002 and 2015. We identified seven pediatric patients who underwent sHKTx at our center. Mean age at time of sHKTx was 13.7 years and 85.7% were re‐graft patients. 57.1% were sensitized with cPRA >50% and another 57.1% had preformed donor‐specific antibody. Five‐year renal allograft survival and patient survival was 85.7% for both end‐points. The remaining six patients are all alive (mean follow‐up 78.5 months) with good kidney and heart function. sHKTx in a population with increased immunological risk can be associated with good long‐term outcomes and offers potential guidance to the pediatric transplant community where data are limited.     

Long‐term outcomes of pediatric kidney transplant recipients with a pretransplant malignancy

A childhood malignancy can rarely progress to ESRD requiring a KT. To date, few reports describe long‐term outcomes of pediatric KT recipients with a pretransplant malignancy. Between 1963 and 2015, 884 pediatric (age: 0‐17 years old) recipients received 1055 KTs at our institution. KT outcomes were analyzed in children with a pretransplant malignancy. We identified 14 patients who had a pretransplant malignancy prior to KT; the majority were <10 years old at the time of KT. Ten (71%) patients received their grafts from living donors, the majority of which were related to the recipient. Wilms' tumor was the dominant type of pretransplant malignancy, seen in 50% of patients. The other pretransplant malignancy types were EBV‐positive lymphoproliferative disorders, non‐EBV‐positive lymphoma, leukemia, neuroblastoma, soft‐tissue sarcoma, and ovarian cancer. Ten of the 14 patients received chemotherapy as part of their pretransplant malignancy treatment. Graft survival at 1, 3, and 5 years was 93%, 83%, and 72%, respectively. Patient survival at 1, 5, and 10 years was 100%, 91%, and 83%, respectively. Six (40%) patients suffered AR following KT; half of them had their first episode of AR within 1 month of KT. Our single‐center experience demonstrates that pediatric KT recipients with a previously treated pretransplant malignancy did not exhibit worse outcomes than other pediatric KT patients.     

Transplantation of adult‐sized kidneys in low‐weight pediatric recipients achieves short‐term outcomes comparable to size‐matched grafts

Goldsmith PJ, Asthana S, Fitzpatrick M, Finlay E, Attia MS, Menon KV, Pollard SG, Ridgway DM, Ahmad N. Transplantation of adult‐sized kidneys in low‐weight pediatric recipients achieves short‐term outcomes comparable to size‐matched grafts.
Pediatr Transplantation 2010: 14:919–924. © 2010 John Wiley & Sons A/S. Abstract: Low‐weight pediatric recipients are disadvantaged by scarcity of size‐matched donors. ASK have been successfully used for pediatric recipients. We report the results of renal transplantation using ASK in low‐weight pediatric recipients and compare outcomes in weight‐matched and unmatched donor–recipient pairs. The outcomes of renal transplants using ASK grafts in low‐weight (<20 kg) recipients from a single center over a 10‐yr period were reviewed. Two groups, comprising recipients of grafts from weight‐matched and mismatched donors, were compared. Primary outcome was one‐yr graft survival. Secondary outcomes were one‐ and two‐yr calculated eGFR, changes in recipient body weight, perioperative cardiovascular stability, rates of AR and DGF. Twenty‐three low‐weight recipients were transplanted. Eleven received ASK grafts from high‐weight donors and 12 grafts from low‐weight donors. One patient in each group had early graft loss. No significant difference was observed in rates of DGF, AR, one‐yr graft or patient survival and perioperative cardiovascular parameters. ASK with considerable donor:recipient weight discrepancies can be safely transplanted into small pediatric recipients with comparable outcomes to grafts with less weight discrepancy.     

Laparoscopic donor nephrectomy for the pediatric recipient population: Risk factors for adverse outcomes

Kidney transplantation is the optimal treatment of ESRD in children. Some studies have reported inferior outcomes in recipients of LDN allografts who are ≤5 yr of age. We performed a retrospective review of pediatric recipient outcomes of 110 LDN allografts at our institution and examined predictors of adverse outcomes. Subgroup analysis was performed by dividing recipients into three age categories: 0–5 yr, 6–17 yr, and ≥18 yr. There was no significant difference between incidences of DGF or ARE between groups. Kaplan–Meier analysis demonstrated 100% allograft survival in 0‐ to 5‐yr‐old recipients, nearly reaching statistical significance (p = 0.07) for outcome superior to that of the two older age groups. Pretransplant HD was associated with increased risk of DGF (p = 0.05). Significant risk factors for ARE were recipient weight >15 kg (p = 0.033) and multiple renal arteries (p = 0.047). Previous ARE was associated with an increased risk of allograft failure (p = 0.02). LDN is not associated with increased risk of DGF, ARE, or allograft failure in the youngest recipients. These findings support an aggressive pursuit of preemptive transplantation even in the youngest pediatric allograft recipients.     

Long‐term outcome of pediatric kidney transplantation: A single‐center experience from Greece

Pediatric kidney Tx has critically altered the outcome in ESRD pediatric patients. The aims of this study were to determine long‐term graft and patient survival in a homogeneous ethnic population. We reviewed the medical charts of pediatric kidney Tx performed between 1990 and 2012 in Greece. Seventy‐five kidney Txs were performed from LRD and 62 from DD. The 10‐ and 20‐yr graft survival was higher in LRD Tx compared with DD Tx. Both patient and graft survival at 10 and 20 yr after Tx were similar in LRD Tx from grandparents compared with parents (92.9% vs. 93.4% 20‐yr patient survival, 71.4% vs. 78.7% and 57.1% vs. 72.1%, 10‐ and 20‐yr graft survival, respectively). However, there was a decreasing tendency in LRD Tx rates in period 2001–2012 compared with period 1990–2000 (47.1% vs. 62.7%). Risk factors for poor five‐yr graft survival were DD Tx, and induction treatment with ALG compared with basiliximab, but their effect attenuated at 10 yr after Tx. In conclusion, Tx from LRD may offer efficient survival outcomes irrespective of donor age, suggesting that even older LRD could be an excellent option for the 1st kidney Tx in children and adolescents.     

Living donor kidney transplantation in pediatric recipients

Living donor kidney transplantation has increased in frequency in pediatric patients, accounting for 43% of cases performed between 1987 and 1991, and 52% of cases performed between 1987 and 2004 in North America. Patient survival has remained excellent over the years, and is currently over 96% at five years. Graft survival has improved over the years, and is currently over 95% at one year. Rejection rates have fallen over the years, and are currently <25% overall, with selected centers having very low rejection rates. The reasons for these improved outcomes are likely related to improvements in maintenance immunosuppression, which include a transition from cyclosporine to tacrolimus-based regimens, and from azathioprine to mycophenolate mofetil or sirolimus as adjunctive agents. Steroid withdrawal and steroid avoidance are beginning to be utilized by several centers, with excellent early outcomes. Finally, while there may be center effect/learning curve issues involved, the type of donor nephrectomy has recently been shown to influence early outcomes, particularly in very young recipients.     

Influence of graft size matching on outcomes of infantile living donor liver transplantation

We aimed to assess the impact of size mismatching between grafts and recipients on outcomes of infants or small children after LDLT. Between October 2006 and December 2014, 129 LDLT recipients weighing no more than 8 kg were retrospectively analyzed. The entire cohort was categorized into three groups by GRWR: GRWR<3.0% (group A, n = 38), 3.0%≤GRWR<4.0% (group B, n = 61), and GRWR≥4.0% (group C, n = 30). Baseline characteristics were similar among groups A, B, and C. Compared with groups A and B, post‐transplant alanine aminotransferase and aspartate aminotransferase within seven days were significantly higher in group C; however, differences between total bilirubin and albumin after transplantation were not prominent. Moreover, incidences of surgical complications, perioperative deaths, infections, and acute rejections were all comparable among the three groups. Five‐yr patient survival rates for groups A, B, and C were 89.5%, 88.9%, and 81.6%, respectively (p = 0.872), and the graft survival rates were 89.5%, 86.6%, and 81.6%, respectively (p = 0.846). In conclusion, GRWR between 1.9% and 5.8% would not cause noticeable adverse events for infantile LDLT recipients ≤8 kg. However, there is still a role for considering reduction in the graft mass as an applicable strategy in selected cases.     

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.     

Hyperammonemia in ornithine transcarbamylase‐deficient recipients following living donor liver transplantation from heterozygous carrier donors

Ornithine transcarbamylase deficiency (OTCD) is a urea cycle disorder of X‐linked inheritance, affecting the detoxification of excess nitrogen and leading to hyperammonemia (hyper‐NH₃). Living donor liver transplantation (LDLT) has been applied for the treatment of OTCD. This case series retrospectively reviewed two OTCD patients who experienced hyper‐NH₃ following LDLT. The first case was a 5‐year‐old girl who had onset of OTCD at 2 years of age. Ornithine transcarbamylase (OTC) enzyme activity was 62% for the donor and 15% for the recipient. The patient suffered from recurrence of hyper‐NH₃ within 2 months following LDLT. The second case was a 5‐year‐old girl who had onset of OTCD at 3 years of age. OTC enzyme activity was 42.6% for the donor and 9.7% for the recipient. The patient suffered hyper‐NH₃ for 12 days starting on the date of surgery. Both of the patients transiently required continuous veno‐venous hemodialysis; however, they are currently doing well without intensive medical treatment. The use of asymptomatic OTCD heterozygous donors in LDLT has been accepted with careful examination. However, an OTCD heterozygous carrier donor should be avoided if there is another donor candidate, due to the potentially fatal condition of hyper‐NH₃ following LDLT.     

IGG3 anti‐HLA donor‐specific antibodies and graft function in pediatric kidney transplant recipients

Anti‐HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a single‐center retrospective chart review of pediatric KT recipients with anti‐HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty‐six patients (mean age 15.4y) with DSAs initially detected 1 month‐14.3 years post‐transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty‐two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3‐ patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97‐55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA‐positive pediatric KT recipients.     

Longitudinal analysis of living donor kidney transplant rates in pediatric candidates in the United States

Among adults, living donor kidney transplant rates began declining in the United States after 2004 but whether a similar decline is occurring in the pediatric candidates has not been well studied. Share 35, a change in allocation rules implemented in October of 2005, may also have influenced rates of living donation. We sought to determine whether a decline in rates was occurring in pediatric candidates and whether the Share 35 program was the cause of the decline. All children listed for a kidney transplant or transplanted with a living donor without listing between 1996 and 2011 were identified in the United States (N=14 911) of which 6046 had received a living donor transplant during follow‐up. Kaplan‐Meier analysis showed a decline in living donor rates in candidates listed after 2001. Logistic regression analysis for living donor kidney transplantation confirmed the timing of the drop but also showed that changes in candidate demographics and center listing practices were impacting rates. A large drop in parental donation was the main cause for the drop. The rate of living donor transplant among pediatric candidates declined after 2001 predating by 4 years the implementation of Share 35, suggesting that factors other than changes in allocation rules are responsible for the decline.