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.

HNF1B Mutations Are Associated With a Gitelman-like Tubulopathy That Develops During Childhood.

BACKGROUND: Mutations in the transcription factor hepatocyte nuclear factor 1B (HNF1B) are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was discriminatory only in adult, but not in pediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age. METHODS: We performed a retrospective analysis of clinical, biochemical, and genetic results of pediatric patients with renal malformations tested for HNF1B mutations, separated into 4 age groups. Values were excluded if concurrent estimated glomerular filtration rate (eGFR) was <30 ml/min per 1.73 m2, or after transplantation. RESULTS: A total of 199 patients underwent HNF1B genetic testing and mutations were identified in 52 (mut+). The eGFRs were comparable between mut+ and mut- in any age group. Although median plasma magnesium concentrations differed significantly between mut+ and mut- patients in all age groups, overt hypomagnesemia was not present until the second half of childhood in the mut+ group. There was also a significant difference in median potassium concentrations in late childhood with lower values in the mut+ cohort. CONCLUSIONS: The abnormal tubular electrolyte handling associated with HNF1B mutations develops with age and is not restricted to magnesium, but consistent with a more generalized dysfunction of the distal convoluted tubule, reminiscent of Gitelman syndrome. The absence of these abnormalities in early childhood should not preclude HNF1B mutations from diagnostic considerations.

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.

The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood.

BACKGROUND AND OBJECTIVES: A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained. RESULTS: The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories. CONCLUSIONS: This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN.

Vascular access-related infection in nocturnal home hemodialysis.

Frequent hemodialysis is associated with increased vascular access adverse events. We hypothesized that bacteremia would be more frequent in patients with central venous catheter (CVC) than arteriovenous fistula or arteriovenous graft (AVF/AVG) in nocturnal home hemodialysis (NHHD). We reviewed blood culture reports and concurrent clinical data for a cohort of one hundred eighty-seven NHHD patients between January 1, 2006 and June 30, 2012. The primary outcome was time to first bacteremia, technique failure, or death after commencing NHHD. Types of bacteremia and clinical consequences were analyzed. Analyses were adjusted for a priori defined confounders. One hundred eighty-seven patients were included with a total follow up of six hundred five patient years. Initial vascular access was AVF in seventy-eight (42%) patients, AVG in eleven (6%) patients, and CVC in ninety-eight (52%) patients. A total of 79.3% of patients with a CVC reached the composite endpoint of bacteremia, technique failure, or death in the study period; 44.5% of patients with an AVF or AVG reached this composite endpoint. Adjusted time to first bacteremia, technique failure, or death was significantly shorter in patients with initial CVC access (hazard ratio 2.42, 95% confidence interval 1.50-3.90, p < 0.001). Risk factors for bacteremia were comorbid status quantified by the Charlson Comorbidity Index (p < 0.001) and diabetes (p < 0.001). Coagulase negative staphylococcus was the commonest organism cultured accounting for 51.4% bacteremias. The second commonest organism was staphylococcus aureus (20.3% bacteremias). Patients undergoing NHHD with a CVC have a shorter duration to first infection, technique failure, or death than those with permanent vascular access.

Factors influencing choice of renal replacement therapy in European paediatric nephrology units.

BACKGROUND: Many factors may impact upon choice of renal replacement therapy (RRT) for children and adolescents, including patient and family choice, patient size and distance from the renal centre as well as logistic issues such as facilities and staffing at the unit. We report a survey of factors influencing treatment choice in 14 European paediatric nephrology units. METHODS: A questionnaire was developed by consensus and completed by 14 members of the European Paediatric Dialysis Working Group on facilities, staffing and family assessments impacting on choice of therapy as well as choice of therapy for 97 patients commencing initial RRT in 2011. RESULTS: All units offered all modalities of RRT, but there were limitations for pre-emptive transplantation (PET) and largely adult surgical dependence for creation of arteriovenous fistulae and transplantation. The average waiting time for a deceased donor kidney was 18.5 (range 3-36) months. Full time dietetic support was available in six of the 14 units. There was no social worker, psychology, play therapy or teaching support in three, two, seven and four units, respectively. Assessment by other members of the multidisciplinary team and home visits before choice of therapy was carried out in 50 % of units, and although all patients were discussed at team meetings, the medical opinion predominated. In terms of types of RRT, 50 % of patients were commenced on chronic peritoneal dialysis (PD), 34 % on haemodialysis (HD) and 16 % underwent pre-emptive transplantation (PET). Chronic PD predominated in patients aged <5 years and HD predominated in those aged >10 years. Patient and family choice and age or size of patient were predominant factors in choice of therapy with a predictable decline in renal function favouring PET and social factors HD. CONCLUSIONS: Chronic peritoneal dialysis predominated as primary choice of RRT, especially in younger children. The PET rates remain low. The influence of surgeons predominanted, and national transplant rules may be significant. Most units had insufficient multiprofessional support, which may impact upon initial choice of therapy as well as sustaining families through RRT.

Unilateral multicystic dysplastic kidney: does initial size matter?

BACKGROUND: We report the long-term follow-up of children with antenatally detected unilateral multicystic dysplastic kidney (MCDK) who were followed between 1985 and 2009. METHODS: Involution rates were documented over time based on the initial size of the MCDK, as documented on postnatal ultrasound (USS), as well as long-term complications and renal function. RESULTS: In 323 patients (182 male), 10 % of MCDK had involuted, as evidenced on the first postnatal USS, with survival function analysis showing the probability of complete involution to be 35 % in 249 patients by 2 years of age, 47 % in 180 patients by 5 years of age and 62 % in 94 patients by 10 years of age. There was a significant difference in the involution rates of MCKD at the 10-year follow-up between MCDK with an initial size of >5 cm versus MCDK with an initial size of ≤5 cm (p < 0.0001). No patients in the whole cohort developed sustained hypertension or malignancy during a median follow-up of 10.1 years (range 0.3-15.4 years). Median estimated glomerular filtration rate (eGFR) in 76 patients (7 at 5 years, 69 at 10 years) was 93 ml/min/1.73 m(2) (range 46-175 ml/min/1.73 m(2)), with 40 (53%) having an eGFR of between 90 and 140 ml/min/1.73 m(2). Twenty-three (30 %) of the 76 patients at 10 years had normal eGFR (90-140 ml/min/1.73 m(2)) as well as complete involution of the MCDK, compensatory hypertrophy of the contralateral kidney, no proteinuria and no hypertension. CONCLUSIONS: Larger MCDK at birth are less likely to involute during the first decade of life. However, conservative management remains justified due to the lack of complications. A minority of patients fulfil current criteria for discharge from specialty follow-up at 10 years.

Vascular access: choice and complications in European paediatric haemodialysis units.

BACKGROUND: European and U.S. guidelines emphasise that permanent vascular access in the form of arteriovenous fistulae (AVF) or grafts (AVG) are preferable to central venous catheters (CVC) in paediatric patients on long-term haemodialysis. We report vascular access choice and complication rates in 13 European paediatric nephrology units. METHODS: A survey of units participating in the European Pediatric Dialysis Working Group requesting data on type of vascular access, routine care and complications in patients on chronic haemodialysis between March 2010 and February 2011. RESULTS: Information was complied on 111 patients in 13 participating centres with a median age of 14 (range 0.25-20.2) years. Central venous catheters were used in 67 of 111 (60%) patients, with 42 patients (38%) having an AVF and two patients (2%) having an AVG. Choice of vascular access was significantly related to patient age, with patients with AVF/AVG having a median age of 16 years compared to 12 years for patients with CVCs (p < 0.001). Routine CVC exit site care and catheter lock solution use differed between centres. CVC infections requiring intravenous antibiotics were reported at a rate of 1.9 and exit site infections at a rate of 1.8 episodes/1000 catheter days. Overall infective complications necessitating CVC change occurred at a rate of 0.9 episodes/1000 catheter days. No infective complications were reported in patients with AVF/AVG access. The rate of CVC infections requiring intravenous antibiotics was significantly lower in patients in whom CVC exit sites were cleaned weekly as opposed to every dialysis session (relative risk with every session cleaning vs. weekly cleaning 2.58, 95% confidence interval 1.17-5.69). Catheter malfunction (inadequate blood flow) was a more prevalent complication necessitating 22.4 thrombolytic interventions/1000 catheter days and 2.1 CVC changes/1000 catheter days. CONCLUSIONS: Central venous catheters remain the predominant choice of vascular access in Europe despite problems of malfunction and infection. AVF/AVG were predominantly used in adolescents without reported complications. More regular exit site cleaning may predispose to CVC infection, but this observation requires prospective evaluation.