Fibroblast growth factor-23 and chronic allograft injury in pediatric renal transplant recipients: a Midwest Pediatric Nephrology Consortium study.

The chronic kidney disease-mineral bone disorder (CKD-MBD) produces fibroblast growth factor-23 (FGF-23) and related circulating pathogenic factors that are strongly associated with vascular injury and declining kidney function in native CKD. Similarly, chronic renal allograft injury (CRAI) is characterized by vascular injury and declining allograft function in transplant CKD. We hypothesized that circulating CKD-MBD factors could serve as non-invasive biomarkers of CRAI. We conducted a cross-sectional, multicenter case-control study. Cases (n = 31) had transplant function >20 mL/min/1.73 m(2) and biopsy-proven CRAI. Controls (n = 31) had transplant function >90 mL/min/1.73 m(2) and/or a biopsy with no detectable abnormality in the previous six months. We measured plasma CKD-MBD factors at a single time point using ELISA. Median (range) FGF23 levels were over twofold higher in CRAI vs. controls [106 (10-475) pg/mL vs. 45 (8-91) pg/mL; p < 0.001]. FGF23 levels were inversely correlated with transplant function (r(2) = -0.617, p < 0.001). Higher FGF23 levels were associated with increased odds of biopsy-proven CRAI after adjusting for transplant function, clinical, and demographic factors [OR (95% CI) 1.43 (1.23, 1.67)]. Relationships between additional CKD-MBD factors and CRAI were attenuated in multivariable models. Higher FGF23 levels were independently associated with biopsy-proven CRAI in children.

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

Kidney transplantation in the United States: economic burden and recent trends analysis.

OBJECTIVE: As kidney transplant is the preferred mode of management of advanced kidney disease and economic trends for kidney transplant procedures are not well known, data were analyzed to assess these trends. DATA SOURCE: Annual data for 1998 to 2008 from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality were used to analyze characteristics of patients discharged from hospitals in the United States with kidney transplant as the primary procedure. DATA SYNTHESIS/RESULTS: The population more than 65 years old had the most significant increase in hospitalizations for kidney transplant procedures (P< .01). The mean length of stay decreased by 2.8 days over the period studied (P= .02). Mean hospital charge increased despite a decrease in length of stay resulting in a 225% increase in charge per day of hospitalization, from $6907 in 1998 to $22 484 in 2008. The national aggregate hospital charges for kidney transplant procedures rose from $0.9 billion in 1998 to $3.1 billion in 2008. Kidney transplant was overall ranked sixth by mean cost per hospitalization and ranked seventh by mean charge per hospitalization among the Clinical Classification Software's Services and Procedures in this database in 2008. CONCLUSION: Despite shorter hospital stays, the economic burden of kidney transplants increased from 1998 to 2008.

Continuous infusion of a standard combination solution in the management of hyperkalemia.

BACKGROUND: Hyperkalemia, due to its effect on cardiac conductivity, is a potentially life-threatening electrolyte abnormality. Multiple therapeutic agents may be used alone or in combination for its prompt management. METHODS: We report on the safety and efficacy of continuous infusion of a solution containing fixed concentrations of calcium gluconate, insulin, dextrose and sodium acetate (HyperK-Cocktail) for the treatment of hyperkalemia. This solution is prepared at our institution and is infused parenterally until the plasma potassium level stabilizes. Twenty-one consecutive hyperkalemic patients managed with HyperK-Cocktail on 23 occasions are reported. RESULTS: None of the subjects had intravenous extravasation injuries, hypernatremia, hypocalcemia, hypercalcemia or alkalosis during HyperK-Cocktail infusion. Transient hyperglycemia developed in nine subjects and hypoglycemia in one subject. The decrease in serum potassium was similar in the initial hour when compared to prior studies using a beta-agonist and/or insulin and glucose; a larger decrease was present from 2 to 8 h with the HyperK-Cocktail. The plasma potassium decreased by a mean of 1.0, 1.7, 2.1 and 2.1 mmol/L at 1, 2, 4 and 8 h, respectively. The mean serum potassium at hours 1-8 was significantly lower than the initial level. CONCLUSION: The results of our study demonstrated that HyperK-Cocktail is a safe and effective combination therapy for children with hyperkalemia.

The role and future challenges for recombinant growth hormone therapy to promote growth in children after renal transplantation.

Chronic kidney disease can severely impair linear growth in children. For many children, growth improves after renal transplantation, but for some, growth velocity remains low and for others, catch-up growth is insufficient to compensate for the deficit imparted by renal disease in the preceding years. Inadequate final adult height after renal transplant is multifactorial and can adversely affect the quality of life (QOL), psychosocial development and long term prospects for these children as they grow into adulthood. Growth failure after renal transplant requires thorough evaluation and its management in renal transplant recipients can involve improved nutritional intake, correction of metabolic acidosis, treatment of secondary hyperparathyroidism, steroid-sparing immunosuppression and/or use of recombinant human growth hormone (rGH). Treatment with rGH after renal transplant has been evaluated by a limited number of clinical trials suggesting efficacy and safety for this treatment strategy. Several important clinical questions regarding rGH use in children post-renal transplant remain unanswered.

A 9-Day-Old With Weight Loss and Diarrhea.

A 9-day-old infant girl presented with diarrhea and weight loss of 19% since birth. She was born via spontaneous vaginal delivery at 39 weeks' gestation to a mother positive for group B Streptococcus who received adequate intrapartum prophylaxis. The infant was formula-fed every 2 to 3 hours with no reported issues with feeding or swallowing. The infant had nonmucoid watery stools ∼5 to 15 times per day. Her family history was significant for hypertrophic cardiomyopathy in several of her family members. Her initial vital signs and physical examination were normal. Laboratory data on hospital admission showed a normal complete blood cell count, but her chemistry analysis revealed significant hypernatremia, hyperkalemia, metabolic acidosis, and acute kidney injury. Her hypernatremia was resistant to fluid management. In this article, we discuss the infant's hospital course, our clinical thought process, and how we arrived at our final diagnosis.

Growth in chronic kidney disease.

Poor growth is a common sequela of CKD in childhood. It not only affects the psychosocial development of a child but also has significant effects even in the adult life. The multifactorial etiology and severe consequences of growth failure in CKD warrant evaluation of all the modifiable and nonmodifiable causes. Treatment strategies must be directed toward the specific factors for each child with CKD. Among the various metabolic, nutritional, and hormonal disturbances complicating CKD, disordered growth hormone (GH) and insulin-like growth factor-1 axis are important contributors toward poor growth in children with CKD. CKD is recognized as a state of GH resistance rather than GH deficiency, with multiple mechanisms contributing to this GH resistance. Recombinant GH (rGH) therapy can be used in this population to accelerate growth velocity. Although its use has been shown to be effective and safe in children with CKD, there continues to be some uncertainty and reluctance among practitioners and families regarding its usage, thereby resulting in a surprisingly low use in children with CKD. This review focuses on the pathogenesis of growth failure, its effect, and management strategies in children with CKD.