Favorable Outcome After Single-kidney Transplantation From Small Donors in Children: A Match-controlled CERTAIN Registry Study.

BACKGROUND: Kidney transplantation (KTx) from small donors is associated with inferior graft survival in registry studies, whereas single-center studies show favorable results. METHODS: We compared 175 pediatric KTx from small donors ≤20 kg (SDKTx) with 170 age-matched recipients from adult donors (ADKTx) from 20 centers within the Cooperative European Paediatric Renal Transplant Initiative registry. Graft survival and estimated glomerular filtration rate (eGFR) were analyzed by Cox regression and mixed models. Detailed data on surgical and medical management were tested for association with graft survival. RESULTS: One-year graft survival was lower after SDKTx compared with ADKTx (90.9% versus 96.5%; odds ratio of graft loss, 2.92; 95% confidence interval [CI], 1.10-7.80; P = 0.032), but 5-y graft survival was comparable (90.9% versus 92.7%; adjusted hazard ratio of graft loss 1.9; 95% CI, 0.85-4.25; P = 0.119). SDKTx recipients had an annual eGFR increase of 8.7 ±â€…6.2 mL/min/1.73 m² compared with a decrease of 6.9 ±â€…5.7 mL/min/1.73 m² in ADKTx recipients resulting in a superior 5-y eGFR (80.5 ±â€…25.5 in SDKTx versus 65.7 ±â€…23.1 mL/min/1.73 m² in ADKTx; P = 0.008). At 3 y posttransplant, eGFR after single SDKTx was lower than after en bloc SDKTx (86.6 ±â€…20.4 versus 104.6 ±â€…35.9; P = 0.043) but superior to ADKTx (68.1 ±â€…23.9 mL/min/1.73 m²). Single-kidney SDKTx recipients had a lower rate of hypertension at 3 y than ADKTx recipients (40.0% versus 64.7%; P = 0.008). CONCLUSIONS: Compared with ADKTx, 5-y graft function is superior in SDKTx and graft survival is similar, even when performed as single KTx. Utilizing small donor organs, preferably as single kidneys in experienced centers, is a viable option to increase the donor pool for pediatric recipients.

Time-Varying Determinants of Graft Failure in Pediatric Kidney Transplantation in Europe.

BACKGROUND: Little is known about the time-varying determinants of kidney graft failure in children. METHODS: We performed a retrospective study of primary pediatric kidney transplant recipients (younger than 18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure. RESULTS: We report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. One thousand six hundred and thirty-eight recipients experienced graft failure, and 168 died with a functioning graft. Between 2011 and 2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased five-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month post-transplant (adjusted hazard ratio, 0.58; 95% confidence interval, 0.46 to 0.73) and remained statistically significant until 12 years post-transplant. Risk factors for graft failure in the first 2 years were deceased donor younger than 12 years or older than 46 years, potentially recurrent kidney disease, and panel-reactive antibody >0%. Other determinants of graft failure included dialysis before transplantation (until 5 years post-transplant), human leukocyte antigen mismatch 2-4 (0-15 years post-transplant), human leukocyte antigen mismatch 5-6 (2-12 years post-transplant), and hemodialysis (8-14 years post-transplant). Recipients older than 11 years at transplantation had a higher risk of graft failure 1-8 years post-transplant compared with other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of post-transplant time and recipient age showed a higher rate of graft failure during the first 5 years post-transplant in adolescents compared with young transplant recipients. In contrast to deceased donor younger than 12 years, deceased donor older than 46 years was consistently associated with a higher graft failure risk. CONCLUSIONS: We report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time post-transplant. The ideal donor age window was dependent on time post-transplant.

Etiology, risk factors and management of hypertension post liver transplantation.

BACKGROUND: Cardiovascular events are one of the most important causes of morbidity and mortality in the long-term follow-up of liver transplant recipients. Hypertension is a significant cardiovascular risk factor that occurs frequently after pediatric liver transplantation. Chronic use of immunosuppressants - mainly calcineurin inhibitors - plays a major role in the development of post-transplant hypertension and circadian disturbances such as flattening of the nocturnal blood pressure dip. This requires special attention in children given the long timeframe during which immunosuppressive therapy is necessary. Careful and structured blood pressure monitoring and adequate treatment of hypertension are essential to optimize the quality of life and life expectancy of pediatric liver transplant patients. However, evidence-based guidelines for monitoring and management of post-transplant hypertension and its complications are lacking. METHODS: We conducted a comprehensive review of the current knowledge and practices concerning post-transplant hypertension. The databases Pubmed, Embase, Web of Science and Google Scholar were scanned with the following keywords: pediatric liver transplantation, immunosuppression, tacrolimus, cardiovascular effects, hypertension, heart function, kidney function, circadian rhythm, mechanism, monitoring, and management. RESULTS: In this review, we describe the incidence and etiology of hypertension in pediatric liver transplant recipients, the underlying mechanisms and characteristics of calcineurin inhibitor-induced hypertension, and the consequences of and risk factors for post-transplant hypertension. We hereby present an overview of the current practices in blood pressure monitoring and antihypertensive treatment as well as an algorithm for the evaluation and management of hypertension post liver transplantation. Finally, we discuss knowledge gaps and suggestions for future research.

Comparison of SARS-CoV-2 seroconversion in children with chronic diseases with healthy children and adults during the first waves of the COVID-19 pandemic.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically diverse, and children have a low risk of developing severe coronavirus disease 2019 (COVID-19). However, children with chronic diseases have a potentially increased risk. Methods: We performed a prospective surveillance study with longitudinal serum SARS-CoV-2 anti-nucleocapsid antibody quantification and questionnaires in pediatric tertiary care patients during the first waves of the COVID-19 pandemic (November 2020-September 2021). The results were compared with those of healthy children and adults from the same geographic area. Results: We obtained 525 samples from 362 patients (M/F ratio of 1.3:1; median age of 11.1 years) comprising children with immune-suppressive or immune-modulating drugs (32.9%), inborn errors of immunity (23.5%), type 1 diabetes mellitus (15.2%), and rheumatic diseases (11.9%). A total of 51 (9.7%) samples were seropositive among 37/351 children (10.5%). Seropositivity increased from 5.8% in November-December 2020 to 21.6% in July-September 2021. Compared with adults, a longitudinal analysis revealed reduced seroprevalence but similar kinetics as in children from the same country. Demographic or social variables and disease characteristics did not correlate with seropositivity. Being obese and household contact with COVID-19-infected individuals significantly increased the odds of infection. The majority of seropositive patients had mild symptoms (21/37). One-third were asymptomatic and/or unaware of having COVID-19 (10/37). Four patients (4/37) needed hospitalization, with good clinical outcomes. Conclusions: Although harboring a chronic disease, we observed a low SARS-CoV-2 incidence in a cohort of pediatric tertiary care patients, comparable with healthy children during the first year of the pandemic. Infection was mostly associated with mild symptoms.

Favorable course of leptospirosis and hantavirus-induced acute tubulointerstitial nephritis under corticosteroid treatment.

BACKGROUND: We present two children with acute tubulointerstitial nephritis (ATIN) caused by leptospirosis in a 12-year-old boy and hantavirus in a 10-year-old girl. The role of glucocorticoids in the management of ATIN triggered by infectious agents is unclear. CASE-DIAGNOSIS/TREATMENT: Both children were hospitalized with jaundice, elevated serum creatinine, and thrombocytopenia. There was no oliguria or hypertension. Urine analysis revealed tubular proteinuria. Kidney biopsy was performed on one patient and showed tubulointerstitial inflammation with mild mesangial proliferation. Both patients were treated with glucocorticoids in view of deteriorating kidney function with respective serum creatinine values of 5.2 and 4.1 mg/dl. Both children exhibited an excellent clinical and biochemical response to treatment. Neither of the patients required dialysis. Positive serology test results indicated a recent leptospirosis and hantavirus infection. CONCLUSIONS: Leptospirosis and hantavirus associated ATIN share common clinical and biochemical features. Due to the low incidence in Europe these infectious causes of kidney dysfunction may be overlooked. Glucocorticoids may be considered in the management of ATIN.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

BACKGROUND: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. METHODS: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. RESULTS: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). CONCLUSION: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hyperparathyroidism Is an Independent Risk Factor for Allograft Dysfunction in Pediatric Kidney Transplantation.

Introduction: Little is known about the consequences of deranged chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. Methods: This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. Results: We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82-4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28-2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71-4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87-2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. Conclusion: Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children.

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope.

Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up.

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.

BACKGROUND: Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. METHODS: In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). RESULTS: Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2 P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. CONCLUSIONS: In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early corticosteroid withdrawal is associated with improved adult height in pediatric kidney transplant recipients.

BACKGROUND: Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with final height (FH). METHODS: Patients who underwent kTx between 1996 and 2018 at below 18 years old in five Belgian and Dutch centers were included. We analyzed the differences between height Z-scores at kTx and 1 year post-transplant (Δ height Z-score) in children with and without corticosteroids at 1 year (CS + /CS -) and with and without rhGH treatment before kTx (rhGH + /rhGH -). Univariable and multivariable linear regression analysis was applied to identify factors associated with height Z-score at 1 year post-kTx, Δ height Z-score, and FH Z-score. RESULTS: A total of 177 patients were included, with median age 9.3 years at kTx. Median height Z-scores pre-kTx and 1 year later in the CS - /rhGH - , CS + /rhGH - , CS - /rhGH + , and CS + /rhGH + groups were - 1.42/ - 0.80, - 0.90/ - 0.62, - 1.35/ - 1.20, and - 1.30/ - 1.60 (p = 0.001). CS use 1 year post-kTx was the only factor associated with Δ height (p = 0.003) on multivariable analysis. CS use at 1 year was the only variable associated with FH (p = 0.014) in children with pre-transplant height Z-score below - 1 (n = 52). CONCLUSIONS: Increase in height Z-score in the first year post-kTx was highest in the CS - /rhGH - group and lowest in the CS + /rhGH + group. The use of corticosteroids at 1 year post-kTx is associated with catch-up growth and in children with pre-transplant height Z-score below - 1 also with final height. A higher resolution version of the Graphical abstract is available as Supplementary information.

Surgical management of Encapsulating Peritoneal Sclerosis (EPS) in children: international case series and literature review.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique. METHODS: Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation. RESULTS: Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / - stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient's stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants. CONCLUSIONS: This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study.

BACKGROUND: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. METHODS: This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. DISCUSSION: The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. TRIAL REGISTRATION: The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

Pediatric Challenges in Robot-Assisted Kidney Transplantation.

Kidney transplantation is universally recognized as the gold standard treatment in patients with End-stage Kidney Disease (ESKD, or according to the latest nomenclature, CKD stage 5). Robot-assisted kidney transplantation (RAKT) is gradually becoming preferred technique in adults, even if applied in very few centra, with potentially improved clinical outcomes compared with open kidney transplantation. To date, only very few RAKT procedures in children have been described. Kidney transplant recipient patients, being immunocompromised, might be at increased risk for perioperative surgical complications, which creates additional challenges in management. Applying techniques of minimally invasive surgery may contribute to the improvement of clinical outcomes for the pediatric transplant patients population and help mitigate the morbidity of KT. However, many challenges remain ahead. Minimally invasive surgery has been consistently shown to produce improved clinical outcomes as compared to open surgery equivalents. Robot-assisted laparoscopic surgery (RALS) has been able to overcome many restrictions of classical laparoscopy, particularly in complex and demanding surgical procedures. Despite the presence of these improvements, many challenges lie ahead in the surgical and technical-material realms, in addition to anesthetic and economic considerations. RALS in children poses additional challenges to both the surgical and anesthesiology team, due to specific characteristics such as a small abdominal cavity and a reduced circulating blood volume. Cost-effectiveness, esthetic and functional wound outcomes, minimal age and weight to undergo RALS and effect of RAKT on graft function are discussed. Although data on RAKT in children is scarce, it is a safe and feasible procedure and results in excellent graft function. It should only be performed by a RAKT team experienced in both RALS and transplantation surgery, fully supported by a pediatric nephrology and anesthesiology team. Further research is necessary to better determine the value of the robotic approach as compared to the laparoscopic and open approach. Cost-effectiveness will remain an important subject of debate and is in need of further evaluation as well.

Body mass index is associated with hyperparathyroidism in pediatric kidney transplant recipients.

BACKGROUND: Hyperparathyroidism persists in up to 50% of pediatric kidney transplant recipients. The aims of this study were to describe the evolution of parathyroid hormone (PTH) in the first year after transplantation and to identify factors associated with hyperparathyroidism. METHODS: This retrospective study included children who underwent kidney transplantation at the University Hospitals of Ghent, Leuven, Rotterdam, or Amsterdam. Data from 149 patients were collected before and up to 12 months after transplantation. Severe hyperparathyroidism was defined as PTH 2-fold above the reference value. Factors associated with hyperparathyroidism and severe hyperparathyroidism were identified using multivariate logistic regression analysis. RESULTS: Before transplantation, 97 out of 137 patients (71%) had hyperparathyroidism. The probability of hyperparathyroidism and severe hyperparathyroidism declined from 0.49 and 0.17 to 0.29 and 0.09 at 3 and 12 months after transplantation, respectively. BMI SDS (ß: 0.509; p = 0.011; 95% CI: 1.122-2.468), eGFR (ß: - 0.227; p = 0.030; 95% CI: 0.649-0.978), and pre-transplant hyperparathyroidism (ß: 1.149; p = 0.039; 95% CI: 1.062-9.369) were associated with hyperparathyroidism 12 months after transplantation. Pre-transplant hyperparathyroidism (ß: 2.115; p = 0.044; 95% CI: 1.055-65.084), defined as intact parathormone (iPTH) levels > 65 ng/l (6.9 pmol/l) or 1-84 PTH > 58 ng/l (6.2 pmol/l), was associated with severe hyperparathyroidism at 3 months. Only eGFR (ß: - 0.488; p = 0.010; 95% CI: 0.425-0.888) was inversely associated with severe hyperparathyroidism at 9 months after transplantation. CONCLUSIONS: Allograft function remains the main determinant of severe hyperparathyroidism after transplantation. Our findings emphasize the importance of BMI and pre-transplant PTH control.

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome.

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

Risk factors for recurrent urolithiasis in children.

PURPOSE: To identify risk factors associated with recurrent kidney stones in a paediatric cohort in a Belgian tertiary centre. STUDY DESIGN AND METHODS: Medical records of children with the first episode of urolithiasis between 1998 and 2016, followed at Ghent University Hospital initially and at least one-year follow-up were retrospectively reviewed. Patient characteristics, past medical history, presenting symptoms, the results of laboratory investigations and the applied management strategy were analysed. The significant variables from the univariate analysis were integrated into a backward conditional multivariate model. RESULTS: Ninety-seven children were included in the analysis, of which 33 (34%) presented with at least one episode of stone recurrence. In the univariate analysis, body mass index (BMI) > 85th percentile and asymptomatic stones at initial presentation were associated with 1.8 and 0.1 times lower risk of recurrent stones, respectively (p = 0.020, 95% confidence interval (CI):0.368-8.749 and p = 0.017, 95% CI:0.014-0.921). In contrast, immobilization resulted in a 10-times higher risk (p = 0.002, 95% CI:1.968-50.005) and the need for technical intervention was associated with a 3.2- times higher risk (p = 0.017, 95% CI:1.297-8.084) of developing recurrent stones. On multivariate analysis only BMI >85th percentile was associated with a 15 times lower risk of stone recurrence (p = 0.030, 95% CI:0.006-0.739). DISCUSSION: A possible explanation of reduced risk in patients with a BMI > 85th percentile may lie in a different metabolic profile. Immobilization as a risk factor can be explained by calcium metabolism, which is influenced by immobilization due to fractures, paralysis or motor disability because it causes resorption of the skeleton resulting in elevated blood calcium levels. This study showed that patients who presented without symptoms when the stones first occurred were less likely to have recurring kidney stones compared with patients with symptoms at initial presentation. When technical intervention was needed, we believe this is partly due to a larger stone burden, however we could not find an evidence-based explanation. The institutional protocol, which allowed to create a database with a limited number of patients, was lost to follow-up. Despite the retrospective setting some data were missing. There might also be a bias because the patients were followed-up at a tertiary centre. Possibly, our conclusions cannot be generalized toward the entire paediatric population. CONCLUSION: Of all the factors investigated in our cohort, BMI >85 th percentile and asymptomatic stones are associated with a lower risk of stone recurrence. Conversely, immobilized patients and those who require technical intervention at initial presentation may benefit from an intense follow-up after the first episode of urolithiasis.

Single-setting robot-assisted kidney transplantation consecutive to single-port laparoscopic nephrectomy in a child and robot-assisted living-related donor nephrectomy: initial Ghent experience.

INTRODUCTION: Kidney transplantation (KT) is the gold-standard treatment for end-stage renal disease (ESRD) in children. Robot-assisted kidney transplantation (RAKT) in adults is becoming increasingly common with potentially improved morbidity compared with open KT. The study objective was to evaluate feasibility and outcomes of RAKT in children. PATIENTS & METHODS: An 8-years-old boy with ESRD received a kidney transplant from his mother. Simultaneously in two operation theatres, the boy underwent single-port (GelPOINT®) right laparoscopic nephro-ureterectomy (LNU), and his mother underwent robot-assisted left donor nephrectomy (RADN).Two full surgical teams were operating at the same time. Subsequently, the boy underwent RAKT, introducing the graft through the GelPOINT®. RESULTS: Total operative time for LNU, RADN, and RAKT was 180, 140, and 195 min, respectively, with warm, cold, and rewarming ischemia times 1.5, 200, and 47 min, respectively. Blood loss was 300, 20, and 50 cc, respectively. No intraoperative complications were noted. Convalescence of both donor and recipient was uneventful, with good kidney function at 1-year follow-up. CONCLUSION: RAKT in children is technically feasible and safe, resulting in excellent graft function. Concomitant nephrectomy can be done laparoscopically through the single-site GelPOINT®. An experienced RAKT team with the full support of pediatric nephrologists is mandatory.

Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: Evolution, risk factors, and impact on patient outcomes.

BACKGROUND: This study aims to investigate the evolution and factors associated with TAC IPV and its impact on patient outcomes in pediatric LT recipients. METHODS: This is a retrospective study including 41 children. The TAC IPV was expressed as the coefficient of variation and was calculated for years 1-5 following LT. The number of missed clinic appointments was used as a surrogate marker for therapy adherence. RESULTS: We identified a decrease in the TAC IPV during the first 3 years after LT (P < 0.01). Serum albumin in the first year (P = 0.03), hematocrit (P = 0.02) and total bilirubin (P = 0.04) in the third year, and therapy adherence (P < 0.01) in the fifth year were associated with TAC IPV. High TAC IPV was associated with biopsy-proven acute allograft rejection (P = 0.04) and the need for biopsy during the first year (P = 0.02). There was a borderline association between TAC IPV and donor-specific antibodies (P = 0.08) and CMV viremia (P = 0.07). High TAC IPV was a predictor of need for liver biopsy and AR with an odds ratio of 1.04 (95% CI 1.0-1.1; P = 0.03) and 1.04 (95% CI 1.0-1.1; P = 0.05), respectively. CONCLUSIONS: Our results highlight the impact of biological factors on TAC IPV during the early LT follow-up and later also therapy adherence. High TAC IPV may be associated with adverse patient outcomes.