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.     

Combined liver‐kidney transplantation in children: Indications and outcome

Abstract: Although it remains a relatively infrequent procedure in children, CLKT has become a viable option for a select group of pediatric patients with severe liver and kidney disease. Most are performed for rare primary diseases such as PH1, but a selected few are performed in the setting of concomitant hepatic and renal failure of uncertain etiology and prognosis. This article reviews the indications for and outcomes following CLKT in children. While it focuses on the specific primary diseases which impact liver and kidney function simultaneously, it addresses the indications based on concomitant hepatic and renal failure, such as seen in the hepatorenal syndrome, as well.     

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.     

Hematopoietic stem cell transplantation and acute kidney injury in children: A comprehensive review

AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Addressing AKI in the context of sinusoidal obstruction syndrome, chemotherapy, thrombotic microangiopathy and hypertension post chemotherapy, glomerulonephritis, and graft versus host disease provides greater insight into renal impairment associated with these HSCT‐related ailments. To obtain a better understanding of AKI among pediatric patients receiving HSCT, we investigated the current literature specifically addressing these areas of concern.     

Pediatric kidney transplantation

Since first performed in 1954, kidney transplantation has evolved as the preferred long-term treatment of children with end stage renal disease (ESRD). The etiology of chronic kidney disease (CKD) and ESRD in children is broad and can be quite complicated, necessitating a multidisciplinary team to adequately care for these patients and their myriad needs. Precise surgical techniques and modern protocols for immunosuppression provide excellent long-term patient and graft survival. This article reviews the many etiologies of renal failure in the pediatric population focusing on those most commonly leading to the need for kidney transplantation. The processes of evaluation, kidney transplantation, short-term and long-term complications, as well as long-term outcomes are also reviewed.     

The effect of donor/recipient body surface area ratio on outcomes in pediatric kidney transplantation

Abstract:  In pediatric kidney transplantation, the effect of inadequate nephron dosing on graft survival remains undetermined. The aim of this study was to assess the use of D/R BSA, as a reliable indicator of adequate nephron dosing, and eventually a tool to optimize pediatric graft allocation. Following Institutional Review Board approval, we reviewed deceased donor pediatric kidney transplantation (N = 156). We divided patients into three groups, based on D/R BSA: A ≤0.8; B 0.81–1.19; C ≥1.2. Five-yr graft survival rates in the groups were: A 82.0%; B 94.9%; C 97.1% (p   =   0.01). Group C had the lowest rate of acute rejection, suggesting a protective effect of increased D/R BSA (group A = 35.7%, group B = 38.9%, group C = 18.8%; p   =   0.029). The logistic regression analysis showed that decreased D/R BSA ratio is a risk factor for loss of graft function, at one and five yr [i.e., group A OR 6 (95% CI 1.14–39.30, p   =   0.015) and OR 4.49 (95% CI 1.46–13.79, p = 0.009), respectively]. We conclude that for pediatric recipients, D/R BSA is a valuable adjunct when determining long-term graft survival. Its utility may avoid an alloimmune-independent risk factor, increasing the long-term protective value of a good matching policy.     

Outcome after kidney transplantation in children with thrombotic risk factors

BACKGROUND: According to the data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), vascular thrombosis accounts for 11.6% of graft losses in pediatric renal transplantation. In adults, inherited and acquired thrombophilic risk factors, e.g. factor V Leiden mutation, have been associated with early graft loss and increased rejection episodes. Data on the impact of these factors on the outcome of children after renal transplantation are rare. METHODS/PATIENTS: Sixty-six pediatric patients awaiting renal transplantation (mean age 10.1 yr) were screened for inherited and acquired risk factors for hypercoagulable disorders (protein C, S, and antithrombin III deficiency, antiphospholipid antibodies, factor V Leiden, prothrombin, and MTHFR mutation) in order to intensify anticoagulation in those with an increased risk for thrombophilia: intravenous heparin was administered with a partial prothrombin time (PTT) prolongation of 50 s for 14 days and switched to low-molecular-weight heparin for another 8 wk before aspirin was introduced for the first year. Patients without hypercoagulable risk factors were treated with heparin without PTT prolongation for 14 days and switched to aspirin immediately afterwards. The results on graft survival, incidence of acute rejection episodes, and long-term renal graft function were analyzed between recipients with and without hypercoagulable risk factors. RESULTS: Thrombophilic risk factors were identified in 27.3% of our patients. No thrombosis occurred. One serious bleeding complication led to a second surgical intervention. The rate of acute rejection episodes was not increased in patients with and without thrombotic risk factors after 90 days (16.7 vs. 25%), 1 yr (22.2 vs. 33.3%), and 3 yr (38.9 vs. 41.7%) of follow-up, respectively (p = n.s.). After a mean follow-up of 3 yr the kidney function was comparable in both groups, with 63.1 in recipients with and 69.8 mL/min/1.73 m(2) in recipients without hypercoagulable risk (p = n.s.). At latest follow-up, three graft losses were found not to be attributed to thrombotic risk factors. INTERPRETATION: Children with thrombophilic risk factors were identified and treated with an intensified anticoagulation regimen after renal transplantation. An increased risk for graft failure, acute rejection episodes, or impaired renal function for pediatric renal transplant recipients with hypercoagulable status was not found.     

Outcome of cadaver kidney transplantation in small children

Cochat P, Castelo F, Glastre C, Martin X, Stamm D, Long D, Lavocat M-P, Hadj-Aïssa A, Lyonnet D, Floret D. Outcome of cadaver kidney transplantation in small children. Acta Pædiatr 1994;83:78–83. Stockholm. ISSN 0803–5253 Small children have often been reported to have poor outcome after kidney transplantation (KT). Recent reports from North America have shown that the use of living-related donors improves patient and graft survival. We report the experience in one centre of primary cadaveric KT using sequential immunosuppression in nine children aged 8–30 months and weighing 5.4–9.8 kg; donors were 0.7–12.3 years old. Four patients had pre-emptive KT and the other five were on peritoneal dialysis; the mean ± SD waiting time was 2.0 ± 2.4 months. Perioperative care has been published previously. The surgical approach was intraperitoneal if the aorta and vena cava were used (n= 7) and extraperitoneal for common iliac vessels anastomosis (n = 2); the duration of surgery was 3.5 ± 0.9 h and the time for vascular anastomosis was 32 ± 6 min. The recipients received ATG, azathioprine, prednisone and delayed administration of cyclosporin A. The patients were followed for 12–98 (median 41) months and showed good graft function (inulin clearance 63–100 ml/min/1.73 m²); only one child with recurrent haemolytic uraemic syndrome lost his graft three months post-transplantation and died after he had received a second graft. None of the recipients required post-transplant dialysis; arterial hypertension involved four children and was related to graft artery stenosis in two. Growth improved by 0.24 ± 0.48 SD score of height per year. Compared to earlier reports on cadaver transplantation in small children (about 40% graft survival after five years) and to the outcome of chronic peritoneal dialysis, the present results are better and appear to be similar to those obtained with living-related donor transplantation.     

Two decades of pediatric kidney transplantation in a multi‐ethnic cohort

Muneeruddin S, Chandar J, Abitbol CL, Seeherunvong W, Freundlich M, Ciancio G, Burke GW, Zilleruelo G. Two decades of pediatric kidney transplantation in a multi‐ethnic cohort.
Pediatr Transplantation 2010: 14:667–674. © 2010 John Wiley & Sons A/S. Abstract: This study evaluated a 20‐yr experience in kidney transplantation in children from a predominantly Hispanic community. A retrospective analysis was carried out in children who received kidney transplants from 1985 to 2005. Of 124 kidney transplants, 81 (65%) were from LD. Racial distribution was Hispanic (48%), followed by AA (24%) and Caucasian (26%). First yr allograft survival was similar in LD and DD and significantly better in LD until seven yr post transplant. eGFR <60 mL/min/1.73 m² at one yr post transplant was associated with a median allograft survival of 3.3 yr, compared to 16 yr in those with eGFR ≥ 60 mL/min/1.73 m² (p < 0.0001). Graft loss in the first five yr was from non‐adherence, recurrence of disease, and infections. Those of AA race were more likely to receive a DD and have low socioeconomic status and the poorest median allograft survival compared to Hispanics and Caucasians (6 vs. ≥15 yr; p < 0.001). In conclusion, this predominantly Hispanic cohort emphasizes the disadvantaged profile of AAs compared to other racial groups. Strategies to improve supportive services and living donations in minority populations need to be developed. Long‐term renal allograft survival is achievable if GFR is maintained >60 mL/min/1.73 m².     

Excellent outcome in infants and small children with thrombophilias undergoing kidney transplantation

One of the most common causes of early graft failure in children undergoing renal transplantation is vascular thrombosis. Numerous risk factors for graft thrombosis have been previously described. Children with various types of thrombophilias such as protein C, protein S and factor V Leiden deficiencies are at an increased risk for vascular thrombosis. Infants and small children with these disorders undergoing renal transplantation have not been well documented in the literature. We reviewed our experience in the diagnosis, peri-operative management and follow up of these patients at our institution. A retrospective analysis of all children undergoing renal transplantation at our institution, using data obtained from the Pediatric Transplant Registry at our institution since May 2000 was performed. The indications for renal transplant included focal segmental glomerulosclerosis, renal dysplasia and reflux nephropathy. One patient had factor V Leiden mutation and two patients had protein S deficiency. Patients were anticoagulated in the peri-operative and post-transplant period. All index transplants were performed with living donor kidneys. There were no adverse outcomes in children with thrombophilias despite having significantly lower weight at the time of transplant vs. children without thrombophilia. The incidence of graft thrombosis in the pediatric renal transplant recipients is high. We identify a potential cause of thrombosis in children not well documented in the literature. A high index of suspicion combined with preoperative screening and diagnosis of thrombophilias and an appropriate treatment plan may decrease the incidence of graft thrombosis in infants and small children undergoing renal transplantation.     

Application of an epitope‐based allocation system in pediatric kidney transplantation

Donor–recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope‐based allocation approach to prospectively exclude donors with high‐level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m², no episodes of rejection, and time to transplant 6.55 months. HLA‐A, HLA‐B, HLA‐DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope‐based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow‐up and larger numbers, but has the potential to reduce anti‐HLA sensitization and improve both graft survival and opportunities for future retransplantation.     

Severe intellectual disability is not a contraindication to kidney transplantation in children

Renal transplantation in children with ID is controversial. Acceptability of these children as candidates varies between programs. Limited outcome data in pediatric renal TXP recipients with cognitive impairment diminish their access to TXP. A retrospective chart review was performed of all children who underwent renal transplantation between January 1, 2002 and June 30, 2012 (N=72). Patients were divided into two groups, those with ID prior to transplantation (n=10) and those without (non‐ID; n=62). Graft survival and BPAR episodes were compared between the two groups using Kaplan‐Meier estimates. Graft survival rates at 3 years post‐TXP were 100% in the ID group and 80% in the non‐ID group (P=.13). Rates of BPAR at 3 years post‐TXP were 10% in the ID group and 27% in the non‐ID group (P=.29). Graft survival and acute rejection‐free survival rates are similar between children with ID and those without. Based on midterm outcomes, there is no apparent contraindication to renal transplantation in pediatric patients with ID. Children with ID should be considered as TXP candidates provided that they have an adequate social support network.     

Indications for combined liver and kidney transplantation in children

Abstract:  A significant number of patients awaiting liver transplantation have associated renal failure and renal dysfunction is associated with increased morbidity and mortality after LT. There has been a recent increase in the number of CLKT in adults. The common indications for CLKT in children are different from those of adults and include metabolic diseases affecting the kidney with or without liver dysfunction and congenital developmental abnormalities affecting both organs. The results are generally encouraging among these groups of patients. Early evaluation and listing of patients before they become severely ill or have major systemic manifestations of their metabolic problem are important.     

Outcome of heart transplantation in pediatric cancer survivors

The aim of this study is to evaluate the outcome of heart transplantation in children surviving malignancies. Pediatric heart transplant recipients were identified using the UNOS database. Follow‐up data including survival and rate of malignancy were analyzed. A total of 7169 children received heart transplants between 1987 and 2011. Of these, 107 (1.5%) survived previous malignancy treatment (group I) and 7062 (98.5%) did not have prior malignancy (group II). Survival after transplant was 92.5%, 90.6%, 80.3%, and 65% at three months, one, five, and 10 yr in group I, similar to the rate in group II (90.1%, 84.4%, 73.8%, and 57.7%). Survival after transplantation was similar between group I and children who underwent OHT secondary to cardiomyopathy in group II. The rate of post‐OHT malignancy in group I was higher than that in group II (14/107(13%) vs. 386/7062 (5.4%), p = 0.001). Children who developed malignancy in group I had similar survival as children who developed malignancy in group II. Post‐transplant survival is similar in children with and without pretransplant malignancy in spite of higher rate of malignancy in children with pretransplant malignancy. OHT appears to be a reasonable treatment option in children who develop end‐stage heart disease after malignancy treatment.     

ABO-incompatible kidney transplantation in children

We designed a new protocol to enable safe ABO-incompatible kidney transplantation. The new protocol utilizes antigen-specific immunoadsorption rather than unspecific plasma exchange to remove existing anti A/B antibodies and rituximab rather than splenectomy to prevent rebound of antibodies. Sixty patients have so far been successfully transplanted with this protocol and 10 of those have been children. When compared with ABO-compatible transplantations, we could not find any differences in success rate, renal function, or adverse events.     

Cardiac magnetic resonance imaging in children with chronic kidney disease and renal transplantation

CV disease is the major cause of death in patients with CKD. Recently, CMR imaging emerges as a complementary method providing advantages in cardiac assessment; however, data on CMR in pediatric CKD are scarce. We performed CMR in 15 children: two with CKD, six on peritoneal dialysis, seven on hemodialysis, and in 18 children 5.1 (0.4-15.4) yr after kidney Tx. Eight children underwent CMR six months before and after Tx. Results are presented as mean z score ± SD. LV EF was higher and in the normal range in Tx patients compared with CKD (-0.3 ± 1 vs. -2.1 ± 1.6, respectively, p < 0.05), whereas RV EF was similar (-0.9 ± 1.4 vs. -0.9 ± 1.8, p = n.s.). End-diastolic and end-systolic LV volume index (0 ± 1.7 vs. 2.1 ± 3.1; 0.2 ± 1.2 vs. 3.1 ± 3.7, both p < 0.05) and LV mass index (1.4 ± 1.5 vs. 3.4 ± 2.9, p < 0.05) were lower in Tx children. All parameters improved in the eight children after Tx. In conclusion, our CMR analysis suggests marked improvement of cardiac function and morphology in children after kidney Tx. CMR might be an appropriate complementary method for measuring detailed cardiac status in children with CKD.     

First experiences of pediatric kidney transplantation in Sri Lanka

KT is the most effective therapeutic option for ESRF. We present our first experiences in a developing country. All children who underwent kidney transplantation since the inception of this program in July 2004 until 30 September 2005 were studied. Their demographic data, operative and peri-operative details, graft and host survival, and drug compliance are described here. Data were collected from patient records and nursing observation records. Eleven children were transplanted during this period (median recipient age 10.75 yr, range: 8-16). The median age of the donors was 41 yr (range: 38-45) and was the mother in eight, father in two and uncle in one. The median (range) follow-up period following transplantation was 12.5 months (7-12). The vascular anastomotic site was aorta and inferior vena cava in nine patients and the cold ischemia time was mean (s.d.) 1.9 h (0.96). All patients received steroids, cyclosporine and MMF for immunosuppression. Hypotension, heart failure and septicemia were common medical complications. Four were treated for acute rejection. Vascular anastomotic leak, burst abdomen, intestinal obstruction, intra-abdominal leak of supra pubic catheter and vesico-ureteric junction obstruction were surgical complications. There were no graft losses or deaths. Despite limited resources good outcomes are possible following renal transplantation in children in developing countries.     

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.     

Physical activity and health related quality of life in children following kidney transplantation

Abstract:  Participation in PA is often diminished in children with CKD. Limited research exists on exercise tolerance/capacity but no studies to date have investigated lifestyle PA and its determinants in these children. The aim of this study was to investigate level of PA and potential physiological and psychological associations in a group of pediatric KTx recipients compared with CS. Twenty KTx and 33 CS participated. PA was measured by PAQ. HRQOL (PedsQL 4.0) and CY-PSPP were also measured. BMI and WC was recorded in all subjects; GFR, BP and immunosuppressants in KTx. Body measurements indicated the two groups were similar: 25% KTx and 24% CS had BMI >85th percentile. KTx were less physically active than CS in total exercise minutes (p = 0.005). CS reported higher HRQOL than KTx (p = 0.001). Higher perceptions of HRQOL were significantly correlated with higher number of steps/day in both groups (p = 0.034). KTx showed significantly lower perceptions of sports competence (p = 0.007) and physical conditioning (p = 0.001) than CS. Higher PAQ activity scores were significantly correlated with higher perceptions of body attractiveness (p = 0.019), Sport (p = 0.003) and Conditioning (p = 0.001). These results suggest that PA may play a role in overall well-being and HRQOL in KTx.