Purpose To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis in 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. Database of clinical BMGL laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these 8 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 the molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.

Background Infants with hyperammonemia can present with nonspecific findings so ordering an ammonia level requires a high index of suspicion. Renal replacement therapy (RRT) should be considered for ammonia concentrations >400 μmol/L since medical therapy will not rapidly clear ammonia. However, the optimal RRT prescription for neonatal hyperammonemia remains unknown. Hemodialysis (HD) and continuous renal replacement therapy (CRRT) are both effective, with differing risks and benefits. Case-Diagnosis/Treatment We present two neonates with hyperammonemia who were later diagnosed with ornithine transcarbamylase (OTC) deficiency and received high-dose CRRT. Using dialysis/replacement flow rates of 8000 ml/hr/1.73m2 (1000 ml/hr or four times higher than the typical rate used for acute kidney injury) the ammonia decreased to <400 μmol/L within 3 hours and <100 μmol/L within 10 hours of CRRT. Conclusions We propose a CRRT treatment algorithm to rapidly decrease the ammonia using collaboration between the emergency department, genetics, critical care, surgery/interventional radiology, and nephrology.

Ambulatory blood pressure monitoring in the initial evaluation of suspected childhood hypertension is highly cost-effective. Awareness of cost saving potential may increase the availability of ambulatory blood pressure monitoring for evaluation of new-onset hypertension.