A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Using Inundation Extents to Predict Microbial Contamination in Private Wells after Flooding Events.

Disaster recovery poses unique challenges for residents reliant on private wells. Flooding events are drivers of microbial contamination in well water, but the relationship observed between flooding and contamination varies substantially. Here, we investigate the performance of different flood boundaries─the FEMA 100 year flood hazard boundary, height above nearest drainage-derived inundation extents, and satellite-derived extents from the Dartmouth Flood Observatory─in their ability to identify well water contamination following Hurricane Florence. Using these flood boundaries, we estimated about 2600 wells to 108,400 private wells may have been inundated─over 2 orders of magnitude difference based on boundary used. Using state-generated routine and post-Florence testing data, we observed that microbial contamination rates were 7.1-10.5 times higher within the three flood boundaries compared to routine conditions. However, the ability of the flood boundaries to identify contaminated samples varied spatially depending on the type of flooding (e.g., riverine, overbank, coastal). While participation in testing increased after Florence, rates were overall still low. With <1% of wells tested, there is a critical need for enhanced well water testing efforts. This work provides an understanding of the strengths and limitations of inundation mapping techniques, which are critical for guiding postdisaster well water response and recovery.

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2.

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH.

Perioperative fluid management and associated complications in children receiving kidney transplants in the UK.

BACKGROUND: Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. METHODS: Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. RESULTS: Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. CONCLUSIONS: This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here. METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months). RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)). CONCLUSIONS: Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.

Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children.

PURPOSE: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1. METHODS: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.73 m2, if aged ≥12 months, or normal serum creatinine, if aged <12 months. The primary end point was percent change in spot urinary oxalate to creatinine ratio (UOx:Cr) from baseline to month 6. Secondary end points included proportion of patients with urinary oxalate ≤1.5× upper limit of normal and change in plasma oxalate. RESULTS: All patients (N = 18) completed the 6-month primary analysis period. Median age at consent was 50.1 months. Least-squares mean percent reduction in spot UOx:Cr was 72.0%. At month 6, 50% of patients (9/18) achieved spot UOx:Cr ≤1.5× upper limit of normal. Least-squares mean percent reduction in plasma oxalate was 31.7%. The most common treatment-related adverse events were transient, mild, injection-site reactions. CONCLUSION: Lumasiran showed rapid, sustained reduction in spot UOx:Cr and plasma oxalate and acceptable safety in patients aged <6 years with PH1, establishing RNA interference therapies as safe, effective treatment options for infants and young children.

Acute paediatric kidney replacement therapies in Europe: demographic results from the EurAKId Registry.

BACKGROUND: Acute kidney injury (AKI), particularly that requiring dialysis, is a severe complication in hospitalized children that is associated with high morbidity and mortality. A prospective European AKI registry (EurAKId registry, NCT02960867) was created to describe the epidemiology and outcomes of paediatric patients treated with acute dialysis. METHODS: Children were recruited who were between 0 and 18 years of age and were treated both in and outside the paediatric intensive care unit (PICU) with peritoneal dialysis (PD), haemodialysis (HD) or continuous kidney replacement therapy (CKRT) for AKI or metabolic derangement, fluid overload (FO), sepsis or respiratory distress. Five age groups and 12 categories of primary diseases were defined. RESULTS: Data on 340 patients were analysed, of whom 86% received dialysis for AKI and 14% for reasons other than AKI. Boys accounted for 60% of the patients. Illness severity was greater in children with cardiac and haematologic diseases than those with kidney diseases. Most patients received dialysis in the PICU (84%). The most frequently used dialysis modality was CKRT (64%), followed by PD (14%) and HD (14%). The overall survival rate was 65%. Survival was significantly lower in children with three comorbidities than in children with no comorbidities (41% and 83%; P < 0.001). CONCLUSIONS: The EurAKId registry is the first prospective registry considering paediatric acute kidney replacement therapies (KRTs) in both critical and non-critical care settings, focusing on the three dialysis modalities in Europe. The clinical indications for KRT have expanded; our population was characterized by critically ill patients, primarily boys, who frequently received dialysis in the PICU with CKRT.

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

BACKGROUND: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. METHODS: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. RESULTS: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher ß2-microglobulin. The HDF cohort had lower ß2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. CONCLUSIONS: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.

Plasma electrolyte imbalance in pediatric kidney transplant recipients.

BACKGROUND: In current practice, pediatric kidney transplant recipients receive large volumes of intravenous fluid intraoperatively to establish allograft perfusion, and further fluid to replace urinary and insensible losses postoperatively. Acute electrolyte imbalance can result, with potential for neurological sequelae. We aimed to determine the incidence and severity of postoperative plasma electrolyte imbalance in pediatric kidney transplant recipients managed with the current standard intravenous crystalloid regimen. METHODS: A retrospective analysis of plasma electrolytes in the first 72 hours post-kidney transplant in 76 children transplanted between January 1, 2015, and January 31, 2018, managed with a standard intravenous fluid strategy used in most UK pediatric transplant centers. RESULTS: Of 76 pediatric transplant recipients of median age 9.9 (range 2.2-17.9) years predominantly managed with 0.45% sodium chloride 5% glucose, 45 (59%) developed acute hyponatremia, 23 (30%) hyperkalemia, and 43 (57%) non-anion-gap acidosis in the postoperative period. Hyperglycemia occurred in 74 (97%) patients. Hyperkalemia was more prevalent in deceased than live donor recipients (P = 0.003) and was significantly associated with non-anion-gap acidosis (P < 0.001). Recipient weight was not associated with overt electrolyte imbalance. CONCLUSION: Postoperative plasma electrolyte imbalance is common in pediatric kidney transplant recipients. Current clinical care strategies mitigate the associated risks of neurological sequelae to some degree. Further studies to optimize intravenous fluid therapy and minimize electrolyte disturbance in this group of patients are needed.

Measurement of iron status in chronic kidney disease.

Anemia is a common complication of chronic kidney disease (CKD) in children, and dysregulation of iron homeostasis plays a central role in its pathogenesis. Optimizing iron status is a prerequisite for effective treatment of anemia. Insufficient iron can lead to inappropriate escalation of the erythropoiesis-stimulating agent (ESA) dose, which is associated with adverse outcomes. Excess iron supplementation also has negative sequelae including free radical tissue damage and increased risk of systemic infection. Notwithstanding the importance of optimizing bioavailable iron for erythropoiesis for children with advanced CKD, achieving this remains challenging for pediatric nephrologists due to the historical lack of practical and robust measures of iron status. In recent years, novel techniques have come to the fore to facilitate accurate and practical assessment of iron balance. These measures are the focus of this review, with emphasis on their relevance to the pediatric CKD population.

Ab-normal saline in abnormal kidney function: risks and alternatives.

Intravenous 0.9% saline has saved countless lives since it was introduced over a century ago. It remains the most widespread crystalloid in both adult and pediatric practice. However, in recent years, evidence of deleterious effects is accruing. These include increased mortality, acute kidney injury (AKI), metabolic acidosis, and coagulopathy. The predominant cause for these sequelae appears to be the excess chloride concentration of 0.9% saline relative to plasma. This has led to development of balanced isotonic solutions such as PlasmaLyte. This review summarizes current evidence for adverse effects of chloride-rich intravenous fluid and considers whether 0.9% saline should still be used in 2018 or abandoned as a historical treatment in favor of balanced crystalloid solutions.

Assessment and management of fluid overload in children on dialysis.

Dysregulation of intravascular fluid leads to chronic volume overload in children with end-stage kidney disease (ESKD). Sequelae include left ventricular hypertrophy and remodeling and impaired cardiac function. As a result, cardiovascular complications are the commonest cause of mortality in the pediatric dialysis population. The clinical need to optimize intravascular volume in children with ESKD is clear; however, its assessment and management is the most challenging aspect of the pediatric dialysis prescription. Minimizing chronic fluid overload is a key priority; however, excessive ultrafiltration is toxic to the myocardium and can precipitate intradialytic symptoms. This review outlines emerging objective techniques to enhance the assessment of fluid overload in children on dialysis and outlines evidence for current management strategies to address this clinical problem.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

Background: Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Methods: Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Results: Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). Conclusions: NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

Beyond playing games: nephrologist vs machine in pediatric dialysis prescribing.

In a recent article in Pediatric Nephrology, Olivier Niel and colleagues applied an artificial intelligence algorithm to a clinical problem that continues to challenge experienced pediatric nephrologists: optimizing the target weight of children on dialysis. They compared blood pressure, antihypertensive medication and intradialytic symptoms in children whose target weight was prescribed firstly by a nephrologist, then subsequently using a machine learning algorithm. Improvements in all outcome measures are reported. Their innovative approach to tackling this important clinical problem appears promising. In this editorial, we discuss the strengths and weaknesses of their study and consider to what extent machine learning strategies are suited to optimizing pediatric dialysis outcomes.

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BACKGROUND: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. METHODS: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). DISCUSSION: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.

Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2.

Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic ß cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2 We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.

Lung ultrasound: a novel technique for detecting fluid overload in children on dialysis.

Background: Optimizing the target weight of infants and children on dialysis remains an important clinical challenge. The use of ultrasound to detect fluid overload in adult patients on dialysis is receiving growing attention. We hypothesized that fluid overload can be quantified in infants and children receiving dialysis using lung ultrasound. Methods: In this prospective observational study, infants and children receiving dialysis for end-stage renal disease (ESRD) or acute kidney injury (AKI) in a regional paediatric nephrology centre were eligible. Lung ultrasound examinations were performed during in-centre dialysis, on home visits or in an outpatient clinic. Fluid overload was assessed by quantifying B-lines on ultrasound and compared with proportional (%) increase in patient weight from the target weight. Results: A total of 142 ultrasound assessments were performed in 23 children. In children with AKI, median B-line score reduced from 5 (range 0-22) at presentation to 1.5 (0-4) at recovery (P = 0.04) with concurrent improvement in fluid overload judged by weight from 7.2 (-1.9 to 15.2)% to 0%. A linear correlation between lung ultrasound B-line score and fluid overload judged by weight was observed in children with AKI (r = 0.83) and ESRD (r = 0.61). Inter-observer variability was acceptable. Conclusions: Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited.

Stop adding insult to injury-identifying and managing risk factors for the progression of acute kidney injury in children.

Acute kidney injury (AKI) is common in children admitted to hospital. Whilst some recover normal kidney function following an acute kidney insult, a significant proportion experience long-term sequelae. The aim of this review is to summarize current understanding of the processes that can lead to sequelae following AKI. Kidney injury, repair, recovery and progression are described. Risk factors for progression are outlined, and potential strategies to stratify the risk of progression in children with AKI are discussed. Clinical management priorities to minimize sequelae are suggested. Looking ahead, novel therapeutic targets are discussed with the potential to accelerate adaptive repair and ameliorate the progression and sequelae of AKI in the future.

Hypomagnesemia and increased risk of new-onset diabetes mellitus after transplantation in pediatric renal transplant recipients.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a significant co-morbidity following kidney transplantation. Lower post-transplant serum magnesium levels have been found to be an independent risk factor for NODAT in adult kidney transplant recipients. METHODS: We undertook a retrospective analysis of risk factors for NODAT in pediatric renal transplant recipients at our institution with the aim of determining if hypomagnesemia confers a significant risk of developing NODAT in this patient population. RESULTS: A total of 173 children with a median age at transplantation of 7.0 (range 1.3-17.5) years were included. Hypomagnesemia was found to be a significant independent risk factor for NODAT (p = 0.01). High trough tacrolimus levels were also independently associated with NODAT (p < 0.001). There was no significant association between NODAT and body mass index at the time of transplantation, monthly cumulative steroid dose or post-transplant cytomegalovirus viremia (p = 0.9, 0.6 and 0.7, respectively). CONCLUSIONS: This study identifies hypomagnesemia as a significant independent risk factor for the development of NODAT in pediatric renal transplant recipients. Given the clear association between hypomagnesemia and NODAT in both adults and children following renal transplantation, further studies are merited to clarify the etiology of this association and to examine the effect of magnesium supplementation on NODAT.