Interobserver agreement of peritoneal dialysis exit site scoring: Results from the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative.

BACKGROUND: Exit site infections are a risk factor for the development of peritonitis in patients on long-term peritoneal dialysis. Visual assessments of an exit site utilising currently available tools (Twardowski and Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS)) are necessary to objectively characterise the appearance of an exit site. The aim of this study was to assess the interobserver agreement of exit site evaluations utilising both exit site scoring tools. METHODS: Exit site evaluations were independently performed by two evaluators during outpatient visits at 13 sites within the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease collaborative. The frequency and percentage of evaluations where both reviewers agreed were calculated. A sub-analysis was performed looking at evaluations where disagreement occurred. RESULTS: A total of 371 paired exit site evaluations were collected over 6 months. For the majority of evaluations (range: 78%-97% Twardowski, 78%-97% MEPPS), both reviewers agreed that no abnormality was present across all domains. When the analysis was restricted to evaluations where at least one reviewer noted an abnormality, interobserver agreement fell across all domains (range: 31%-61% Twardowski, 56%-66% MEPPS). Disagreements more commonly occurred regarding the presence versus absence of an abnormality, rather than a difference in the severity of an abnormality. CONCLUSIONS: Whereas interobserver agreement is high when the appearance of a peritoneal dialysis catheter exit site is characterised as 'normal', interobserver disagreement is common when the appearance of the exit site is 'abnormal'. Further work is warranted to improve interobserver agreement of exit site assessments and to identify domains conferring an increased risk of infection.

Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system.

BACKGROUND: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). METHODS: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal-Wallis analysis were performed using SAS version 9.4. RESULTS: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). CONCLUSIONS: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein.

Good outcomes for arteriovenous fistula with buttonhole cannulation for chronic hemodialysis in children and adolescents.

BACKGROUND: Arteriovenous fistula (AVF) is the preferred access for chronic hemodialysis (HD) in children and adolescents, but central venous catheter use is still high. METHODS: Retrospective chart review of children and adolescents with AVF created between January 2003 and December 2015 was performed to assess primary failure (PF), maturation time, functional primary and functional cumulative patency, and potential risk factors for AVF dysfunction. RESULTS: Ninety-nine AVF were created in 79 patients (54% male; 7-24 years; 16-147 kg) by experienced surgeons. Duplex ultrasonography vein mapping was used to assist with site selection. PF occurred in 17 AVF (17%) in 14 patients. Patient age, gender, ethnicity, underlying disease, time on dialysis, and AVF site were not associated with PF or patency. Coagulation abnormality was positively associated with PF (p = 0.03). Function was achieved in 82 AVF (83%) in 77 patients (97%). Median maturation time was 83 days (range 32-271). AVF were accessed via buttonholes. Functional primary patency was 95%, 84%, and 53% at 1, 2, and 5 years. Overall 1- and 2-year functional cumulative patency was 95%, but lower for small patients 16-30 kg (88%) and those greater than 80 kg (91%). The 5-year patency rate was 80%, but significantly lower for 16-30 kg (59%) and greater than 80 kg (55%). Risk analysis showed significantly better patency for 31-45 kg and 46-80 kg groups (p < 0.01), non-obese BMI (p = 0.01), and buttonhole self-cannulation (p = 0.03). CONCLUSIONS: This study provides more information about successful AVF with buttonhole cannulation in pediatric hemodialysis patients lending additional support for AVF use in pediatrics. A higher resolution version of the Graphical abstract is available as Supplementary information.

Frequency of Bacteremia and Urinary Tract Infection in Pediatric Renal Transplant Recipients.

BACKGROUND: Our primary goal was to determine the frequency of bacteremia and urinary tract infections (UTI) in pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant and to identify clinical and laboratory factors associated with bacteremia. METHODS: We conducted a retrospective cross-sectional study for all pediatric ( < 18 years old) renal transplant recipients seen at 3 large children's hospitals from 2011 to 2018 for suspected infection within 2 years of transplant date, defined as pyrexia ( > 38°C) or a blood culture being ordered. Patients with primary immunodeficiencies, nontransplant immunosuppression, intestinal failure, and patients who had moved out of the local area were excluded. The primary outcome was bacteremia or UTI; secondary outcomes included pneumonia, bacterial or fungal meningitis, respiratory viral infections, and antibiotic resistance. The unit of analysis was the visit. RESULTS: One hundred fifteen children had 267 visits for infection evaluation within 2 years of transplant. Bacteremia (with or without UTI) was diagnosed in 9/213 (4.2%) and UTIs in 63/189 (33.3%). Tachycardia and hypotension were present in 66.7% and 0% of visits with documented bacteremia, respectively. White blood cell (12,700 cells/mm 3 vs. 10,900 cells/mm 3 ; P = 0.43) and absolute neutrophil count (10,700 vs. 8200 cells/mm 3 ; P = 0.24) were no different in bacteremic and nonbacteremic patients. The absolute band count was higher in children with bacteremia (1900 vs. 600 cells/mm 3 ; P = 0.02). Among Gram-negative pathogens, antibiotic resistance was seen to 3rd (14.5%) and 4th (3.6%) generation cephalosporins, 12.7% to semisynthetic penicillins, and 3.6% to carbapenems. CONCLUSIONS: Bacteremia or UTIs were diagnosed in one-quarter of all pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant. Evaluations were highly variable, with one-third of visits not having urine cultures obtained. No single demographic, clinical or laboratory variable accurately identified patients with bacteremia, although combinations of findings may identify a high-risk population.

Good outcomes after pediatric intraperitoneal kidney transplant.

BACKGROUND: Kidney transplantation in small children is technically challenging. Consideration of whether to use intraperitoneal versus extraperitoneal placement of the graft depends on patient size, clinical history, anatomy, and surgical preference. We report a large single-center experience of intraperitoneal kidney transplantation and their outcomes. METHODS: We conducted a retrospective review of pediatric patients who underwent kidney transplantation from April 2011 to March 2018 at a single large volume center. We identified those with intraperitoneal placement and assessed their outcomes, including graft and patient survival, rejection episodes, and surgical or non-surgical complications. RESULTS: Forty-six of 168 pediatric kidney transplants (27%) were placed intraperitoneally in children mean age 5.5 ± 2.3 years (range 1.6-10 years) with median body weight 18.2 ± 5 kg (range 11.4-28.6 kg) during the study period. Two patients (4%) had vascular complications; 10 (22%) had urologic complications requiring intervention; all retained graft function. Thirteen patients (28%) had prolonged post-operative ileus. Eight (17%) patients had rejection episodes ≤6 months post-transplant. Only one case resulted in graft loss and was associated with recurrent focal segmental glomerular sclerosis (FSGS). Two patients (4%) had chronic rejection and subsequent graft loss by 5-year follow-up. At 7-year follow-up, graft survival was 93% and patient survival was 98%. CONCLUSIONS: The intraperitoneal approach offers access to the great vessels, which allows greater inflow and outflow and more abdominal capacity for an adult donor kidney, which is beneficial in very small patients. Risk of graft failure and surgical complications were not increased when compared to other published data on pediatric kidney transplants.

Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients.

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.

A comparison of the buttonhole and rope-ladder AVF cannulation techniques and infection rates within the SCOPE collaborative.

BACKGROUND: Studies regarding hemodialysis (HD) arteriovenous fistula (AVF) cannulation in adults indicate a higher risk of infection with the buttonhole (BH) technique compared to the rope-ladder (RL) technique. Pediatric data on this issue is sparse. METHODS: We compared infection rates within the Standardizing Care to Improve Outcomes in Pediatric End stage kidney disease (SCOPE) centers performing BH cannulation versus RL cannulation of AVF. Generalized linear mixed modeling was used to assess differences in access-related blood stream infection (BSI) and access site infection (ASI) rates between the centers. RESULTS: Data was available from 211 AVF enrollments among 210 children. There were 61 AVF enrollments at 6 BH centers and 150 enrollments at 13 RL centers. Demographics were similar between the two groups. There were 12 total infections in 3383 patient months. BH centers had 3 infections (0 BSI, 3 ASI) and RL centers had 9 infections (5 BSI, 3 ASI). Mean [95% confidence interval] infection rates per 1000 patient months were not different between BH and RL centers (BH: 3.1 [0.6,15.6], RL: 3.2 [1.3,9.4], p = 0.947). A survey was also completed by the BH centers to describe their BH practices. The BH procedure at the majority of sites was characterized by a small patient/nurse ratio and strict antiseptic protocols. CONCLUSIONS: This data provides evidence of a low BSI rate associated with BH cannulation in pediatric HD patients. Further studies are needed to better delineate the differences in the pediatric and adult experience with the BH cannulation technique.

Surgical correction of hydrothorax complicating pediatric peritoneal dialysis.

Hydrothorax complicating continuous cycling peritoneal dialysis (CCPD) is an uncommon event. Its presentation may occur shortly after or years after initiation of dialysis. Surgical intervention offers the advantage of direct visualization and repair of the diaphragmatic defect. Video assisted thoracoscopy surgery (VATS) has been increasingly used in identifying these defects to facilitate this repair. We present 2 pediatric cases who underwent successful direct surgical repair of diaphragmatic defects using VATS with return to CCPD. Initial approach with VATS should be strongly considered in patients in whom a lifetime change in modality has significant repercussions.

Correlation of Venous Oxygen Saturations from Noninvasive Hematocrit Monitoring Using Blood Gas Measured Oximetry in Chronic Pediatric Hemodialysis Patients.

INTRODUCTION: Noninvasive hematocrit monitoring (NIVHM) during pediatric hemodialysis (pedHD) provides data in real time regarding changes in hematocrit and blood volume and also provides venous oxygen saturations. The latter has been proposed to indicate changes in tissue oxygen consumption. It is not known how well NIVHM oxygen saturations (O2sat) approximate blood gas measured oximetry saturation (mO2sat) in the course of pedHD. We aimed to assess the validity and reliability of NIVHM O2sat compared to mO2sat. METHODS: This is a prospective study in 15 patients <21 years old with >90 days on hemodialysis (HD) without congenital heart disease. HD access was fistula (AVF) in 4 patients and tunneled catheters in the remainder. Pulse oximetry (spO2) was continuously monitored; mO2sat was measured via oximetry in a blood gas analyzer and NIVHM O2sat values collected at the start, middle, and end of HD treatment. RESULTS: A total of 45 dyad measurements were obtained. NIVHM O2sat correlated well with mO2sat (R = 0.89, p < 0.0001); the same was seen at pre, mid, and post HD time points (R = 0.86-0.95, p < 0.001). NIVHM O2sat was lower than mO2sat; with catheter as access, the difference was 9.3 ± 8.6 (CI: 12.3-6.22, p < 0.0001) and with AVF was 2.1 ± 0.78 (CI: 2.6-1.7, p < 0.0001). Bland-Altman analysis demonstrated the difference but did not show any systematic bias. Continuous monitor of spO2 showed no hypoxia. DISCUSSION/CONCLUSION: Intradialytic NIVHM O2sat correlates well with mO2sat but yield lower values. Future studies can include NIVHM O2sat changes as a surrogate for central venous O2 saturation changes and potentially yield useful information regarding tissue oxygen consumption in pedHD patients.

Elevated Serum Creatinine: But Is It Renal Failure?

Serum creatinine is typically used to evaluate kidney function. Yet, it is a marker that can only provide estimations of kidney function because it can be influenced by other factors, such as dietary intake. The expanding field of infant formula selection in recent history has given many options for parents who are unable to provide breastmilk. Standard infant formulas and breastmilk generally fall within a select range of creatine content. With greater accessibility to internet-based medical advice (licensed or unlicensed), parents and families have more chances to be exposed to opportunistic websites and opinions that may provide harmful information. In this report, we describe the case of excessive dietary creatine intake in an infant who presented with elevated creatinine while otherwise appearing healthy and having normal cystatin C. After in-depth evaluation of nutritional intake, there was a suspicion for high creatine load of the infant's homemade formula, which was composed of beef liver and various unregulated nutritional powders. Within 12 hours of stopping the infant's homemade formula and providing intravenous fluids, the infant's creatinine normalized. We highlight the importance of in-depth nutrition assessments and education on the health risks associated with improper formula selection.

Characteristics and Clinical Outcomes of Prolonged Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients.

OBJECTIVES: Paralleling improved outcomes in critically ill patients, survival for pediatric acute kidney injury has improved. Continuous renal replacement therapy is the preferred modality to optimize fluid and electrolyte management as well as nutritional support for children developing acute kidney injury in the PICU. However, some patients remain too fragile for transition to intermittent renal replacement therapies and require continuous renal replacement therapy for a prolonged period. Characteristics of this cohort and factors impacting outcomes are not well known. We aimed to describe the characteristics of pediatric patients requiring prolonged continuous renal replacement therapy and evaluate the factors impacting hospital survival. DESIGN: Retrospective chart review. SETTING: Tertiary PICU. PATIENTS: Children requiring prolonged continuous renal replacement therapy. Prolonged continuous renal replacement therapy was defined as continuous renal replacement therapy dependence greater than or equal to 28 days. Primary outcome was hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2013 to 2016, 344 patients received continuous renal replacement therapy, 36 (10%) received continuous renal replacement therapy for greater than or equal to 28 days. Seventeen patients (47%) were female. Overall mortality was 44% (16/36); 69% (11/16) of nonsurvivors died of sepsis. Pediatric Logistic Organ Dysfunction score was significantly higher in nonsurvivors. Mortality rate was significantly higher in patients who were neutropenic at continuous renal replacement therapy start. Neutropenia (defined as absolute neutrophil count < 1,500/mm) at continuous renal replacement therapy start was the only independent predictor of mortality. One in four survivors did not recover renal function and remained dialysis dependent. CONCLUSIONS: Prolonged continuous renal replacement therapy patients are at high risk of nonrecovery of renal function and require close monitoring. The majority of nonsurvivors in the study group died from sepsis. Neutropenia at continuous renal replacement therapy initiation was associated with increased risk of mortality. Progression of underlying disease process could explain the higher death rate in patients with neutropenia; however, inadequate treatment of infectious complications could be another explanation to explore further in future studies.

Cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients below age 5 years
.

BACKGROUND: Management of chronic kidney disease mineral bone disorder (CKD-MBD) in pediatric patients with end-stage renal disease (ESRD) is challenging. While the use of calcimimetics is well-studied in adults on dialysis, few studies have been performed in pediatrics. Little is known about the use of cinacalcet in young children with ESRD. The aim of this study was to report the efficacy and safety of cinacalcet for treatment of secondary hyperparathyroidism in chronic dialysis patients younger than 5 years. MATERIALS AND METHODS: We included children aged < 5 years on chronic dialysis, either hemodialysis (HD) or peritoneal dialysis (PD), who were prescribed cinacalcet for more than 1 month. Retrospective chart review was performed to gather demographics, dialysis prescription, relevant mineral imbalance laboratory parameters, and medications. Data was collected for 6 consecutive months. RESULT: 18 patients (9 male), mean age at initiation of cinacalcet was 2.3 years; 13 PD and 5 HD. Average starting dose of cinacalcet: 6.2 mg daily, 0.55 mg/kg/day. Average time on dialysis was 14.4 months. Parathyroid hormone significantly decreased over the 1st month following initiation of cinacalcet from 929 (IQR 572 - 1,056) to 427 (IQR 256 - 778) pg/mL, p = 0.009. Three patients developed asymptomatic hypocalcemia (Ca < 9.4 mg/dL). Serum phosphorous decreased after initiation, and this was persistent at 6 months. Significant improvement in linear growth was observed while on cinacalcet and growth hormone (GH). CONCLUSION: Cinacalcet can be effectively used in young children on dialysis with minimal side effects. Good linear growth was seen in patients on cinacalcet and GH therapy. Long-term large scale data is necessary to confirm. Institution-based management algorithm incorporating cinacalcet would be helpful to maintain uniformity in role of cinacalcet for management of CKD-MBD.

Successful kidney transplantation in a small child with end-stage renal disease due to angiotensin receptor blocker fetopathy and atretic inferior vena cava.

Kidney transplantation is the treatment of choice in pediatric patients with end-stage renal disease. This population presents technical challenges particularly in those less than 20 kg due to anomalous anatomy, vascular access issues prior to transplantation, and a generally small size for age. Standard allograft outflow is usually achieved utilizing the iliac veins or IVC. When use of the iliocaval system is not feasible, alternative anastomosis must be considered. Herein, we report a case of a pediatric kidney transplantation where successful allograft outflow was achieved using the SMV when he was found to have an atretic IVC intraoperatively. In this setting, use of the portal system was required to achieve adequate allograft outflow. We created a donor iliac graft for added length to anastomose the renal vein with the SMV. In the setting of IVC occlusion with poor drainage, we utilized a patent vessel with larger caliber for outflow to reduce the risk of high venous pressures, allograft failure, venous rotation, and thrombosis. We conclude that the SMV may serve as an alternative outflow tract in the small pediatric patient and provides the vessel caliber needed to reduce the risks of complications.

Peritoneal dialysis catheter outcomes in infants initiating peritoneal dialysis for end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) although rare among infants presents many management challenges. We sought to evaluate factors associated with PD catheter failure among infants initiated on chronic PD. METHODS: A retrospective chart review of all children under two years of age who had PD catheters placed for initiation of chronic PD from 2002 to 2015. Data was extracted for catheter related events occurring within 12 months of catheter placement. Cox and Poisson regression models were used to delineate factors associated catheter complications. RESULTS: Twenty-five infants with median age 18 days had PD catheters placed for chronic dialysis. Common complications included leakage around the exit site (31%), blockage (26%), migration or malposition (23%), catheter-related infections (18%), and other complications (2%). Predictors of initial PD catheter failure were age less than one month at catheter placement (hazard ratio (HR) 7.77, 95% CI, 1.70-35.39, p = 0.008), use of catheter within three days of placement (HR 5.67, 95% CI, 1.39-23.10, p = 0.015) and presence of a hernia (HR 8.64, 95% CI, 1.19-62.36, p = 0.033). In an adjusted Poisson regression model, PD catheter use within three days of placement was the only predictor of any catheter complication over the12 months of follow up. CONCLUSIONS: Use of PD catheters within three days of placement was associated with catheter failure. We recommend that when possible, catheters should be allowed to heal for at least three days prior to use to reduce risk of complications and improve catheter survival.

Exit site and tunnel infections in children on chronic peritoneal dialysis: findings from the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative.

BACKGROUND: The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a quality improvement initiative to reduce dialysis-associated infections. The frequency of peritoneal dialysis (PD) catheter exit site infection (ESI) and variables influencing its development and end result are unclear. We sought to determine ESI rates, to elucidate the epidemiology, risk factors, and outcomes for ESI, and to assess for association between provider compliance with care bundles and ESI risk. METHODS: We reviewed demographic, dialysis and ESI data, and care bundle adherence and outcomes for SCOPE enrollees from October 2011 to September 2014. ESI involved only the exit site, only the subcutaneous catheter tunnel, or both. RESULTS: A total of 857 catheter insertions occurred in 734 children over 10,110 cumulative months of PD provided to these children. During this period 207 ESIs arose in 124 children or 0.25 ESIs per dialysis year. Median time to ESI was 392 days, with 69% of ESIs involving exit site only, 23% involving the tunnel only, and 8% involving both sites. Peritonitis developed in 6%. ESI incidence was associated with age (p = 0.003), being the lowest in children aged < 2 years and highest in those aged 6-12 years, and with no documented review of site care or an exit site score of > 0 at prior month's visit (p < 0.001). Gender, race, end stage renal disease etiology, exit site orientation, catheter cuff number or mobilization, and presence of G-tube, stoma, or vesicostomy were unassociated with ESI incidence. Of the ESIs reported, 71% resolved with treatment, 24% required hospitalization, and 9% required catheter removal, generally secondary to tunnel infection. CONCLUSIONS: Exit site infections occur at an annualized rate of 0.25, typically well into the dialysis course. Younger patient age and documented review of site care are associated with lower ESI rates. Although most ESIs resolve, hospitalization is frequent, and tunnel involvement/catheter loss complicate outcomes.

Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease.

BACKGROUND: Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study. METHODS: This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD. Following a 2-4 week screening phase, pediatric patients with a serum phosphorus level higher than age-appropriate levels were randomized to receive either SC or placebo as powder/tablets in 0.4-1.6 g doses, based on body surface area. The primary efficacy outcome was the change in serum phosphorus from baseline to end of the FDP in the SC versus placebo arms (analysis of covariance). The secondary outcome was mean change in serum phosphorus from baseline to end of DTP by treatment group and overall. Treatment-emergent/serious adverse events (AEs) were recorded. RESULTS: Of 101 enrolled patients (29 centers), 66 completed the study. The majority of patients were adolescents (74%; mean age 14.1 years) and on dialysis (77%). Renal transplant was the main reason for discontinuation. SC significantly reduced serum phosphorus from baseline levels (7.16 mg/dL) during the FDP compared to placebo (least square mean difference - 0.90 mg/dL, p = 0.001) and during the DTP (- 1.18 mg/dL, p < 0.0001). The safety and tolerability of SC and placebo were similar during the FDP, with patients in both groups reporting mild/moderate gastrointestinal AEs during the DTP. CONCLUSIONS: Sevelamer carbonate significantly lowered serum phosphorus levels in hyperphosphatemic children with CKD, with no serious safety concerns identified.

Thrombocytopenia-associated multi-organ failure secondary to hyperglycemic, hyperosmolar non-ketotic syndrome: A case report.

Thrombocytopenia associated multi-organ failure (TAMOF) is a clinical syndrome with features of new onset thrombocytopenia, increased lactate dehydrogenase, and multi-organ failure in critically ill patients. TAMOF can be the initial presentation of an underlying disease process or can develop during the course of illness either during the hospital stay. TAMOF has a high mortality rate if not treated; therefore, early detection is critical. TAMOF has been rarely reported in diabetic ketoacidosis. We are describing the first case of a patient diagnosed with hyperglycemic, hyperosmolar non-ketotic syndrome who developed TAMOF on the third day of his hospital course. In addition to supportive care in the intensive care unit the patient received serial therapeutic plasma exchanges and improved quickly after treatment. Early diagnosis and treatment of TAMOF decreases morbidity and mortality.

Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.

PURPOSE: To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). METHODS: WES was performed in 62 families with CAKUT. WES data were analyzed for single-nucleotide variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). RESULTS: In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development. CONCLUSION: We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.Genet Med 19 4, 412-420.