In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group ...of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.
Telehealth in Pediatric Medicine presents many of the same benefits and challenges noted in adult-based medicine. In terms of health care delivery, the promise of improving access and reducing costs ...using telehealth in Pediatrics, particularly chronic care, is high. The ability to address clinician shortages and provide remote guidance for chronic care pathways from pediatric subspecialists to rural-based referring physicians is a developing model that represents a sustainable and cost-effective strategy to improve pediatric care. The adoption and implementation of consistent telehealth programs require a readjustment of current regulatory rules and a national discussion on reimbursement and compliance standards. Presently, state laws generally define the rules, whereby health systems or practices can use telehealth for patient care and education. Long-term telehealth program development depends on the ongoing value and use case provided by pediatric advocates for this emerging health care delivery model.
Ammonia is an important source of nitrogen and is required for amino acid synthesis. It is also necessary for normal acid-base balance. When present in high concentrations, ammonia is toxic. ...Endogenous ammonia intoxication can occur when there is impaired capacity of the body to excrete nitrogenous waste, as seen with congenital enzymatic deficiencies. A variety of environmental causes and medications may also lead to ammonia toxicity. Hyperammonemia refers to a clinical condition associated with elevated ammonia levels manifested by a variety of symptoms and signs, including significant central nervous system (CNS) abnormalities. Appropriate and timely management requires a solid understanding of the fundamental pathophysiology, differential diagnosis, and treatment approaches available. The following review discusses the etiology, pathogenesis, differential diagnosis, and treatment of hyperammonemia.
Background Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in ...the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. Study Design Prospective observational study. Setting & Participants 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. Predictor Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in L − fluid out L)/(ICU admit weight kg) × 100%. Outcome & Measurements The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. Results 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed ≥ 20% fluid overload. Patients who developed ≥ 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to ≥ 20% and < 20%, patients with ≥ 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7). Limitations This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. Conclusions Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.
Objective To report circuit characteristics and survival analysis in children weighing ≤10 kg enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. Study ...design We conducted prospective cohort analysis of the ppCRRT Registry to: (1) evaluate survival differences in children ≤10 kg compared with other children; (2) determine demographic and clinical differences between surviving and non-surviving children ≤10 kg; and (3) describe continuous renal replacement therapy (CRRT) circuit characteristics differences in children ≤5 kg versus 5-10 kg. Results The ppCRRT enrolled 84 children ≤10 kg between January 2001 and August 2005 from 13 US tertiary centers. Children ≤10 kg had lower survival rates than children >10 kg (36/84 43% versus 166/260 64%; P < .001). In children ≤10 kg, survivors were more likely to have fewer days in intensive care unit prior to CRRT, lower Pediatric Risk of Mortality 2 scores at intensive care unit admission and lower mean airway pressure (Paw ), higher urine output, and lower percent fluid overload (FO) at CRRT initiation. Adjusted regression analysis revealed that Pediatric Risk of Mortality 2 scores, FO, and decreased urine output were associated with mortality. Compared with circuits from children 5-10 kg at CRRT initiation, circuits from children ≤5 kg more commonly used blood priming for initiation, heparin anticoagulation, and higher blood flows/effluent flows for body weight. Conclusion Mortality is more common in children who are ≤10 kg at the time of CRRT initiation. Like other CRRT populations, urine output and FO at CRRT initiation are independently associated with mortality. CRRT prescription differs in small children.
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.
Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral ...renal agenesis can lead to future health issues including end-stage renal disease. Genetic investigations have identified several gene variants that cause RA, including
,
, and
However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans. In this study, we carried out whole exome sequence analysis of two families showing inheritance of an RA phenotype, and in both identified a single candidate gene,
Analysis of a zebrafish
loss-of-function mutant revealed defects in the pronephric kidney just prior to death, and F0 CRISPR/Cas9 mutagenesis of
in the mouse revealed kidney agenesis phenotypes, implicating
in this disorder. GREB1L resides in a chromatin complex with RAR members, and our data implicate GREB1L as a coactivator for RARs. This study is the first to associate a component of the RAR pathway with renal agenesis in humans.
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