An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients.

Calcineurin inhibitors are highly efficacious immunosuppressive agents used in pediatric kidney transplantation. However, calcineurin inhibitor nephrotoxicity (CNIT) has been associated with the development of chronic renal allograft dysfunction and decreased graft survival. This study evaluated 37 formalin-fixed paraffin-embedded biopsies from pediatric kidney transplant recipients using gene expression profiling. Normal allograft samples (n = 12) served as negative controls and were compared to biopsies exhibiting CNIT (n = 11). The remaining samples served as positive controls to validate CNIT marker specificity and were characterized by other common causes of graft failure such as acute rejection (n = 7) and interstitial fibrosis/tubular atrophy (n = 7). MiRNA profiles served as the platform for data integration. Oxidative phosphorylation and mitochondrial dysfunction were the top molecular pathways associated with overexpressed genes in CNIT samples. Decreased ATP synthesis was identified as a significant biological function in CNIT, while key toxicology pathways included NRF2-mediated oxidative stress response and increased permeability transition of mitochondria. An integrative analysis demonstrated a panel of 13 significant miRNAs and their 33 CNIT-specific gene targets involved with mitochondrial activity and function. We also identified a candidate panel of miRNAs/genes, which may serve as future molecular markers for CNIT diagnosis as well as potential therapeutic targets.

Information Quality for Residency Applicants in Fellowship and Residency Electronic Interactive Database (FREIDA) and Program Websites.

Background Today's residency applicants submit more applications than those in the past. To facilitate holistic review, many program directors have encouraged applicants to submit fewer applications. However, whether programs provide sufficient information to help applicants determine where to apply is unclear. Objective To evaluate the frequency of missing information on residency program websites and in the Fellowship and Residency Electronic Interactive Database (FREIDA). Methods We used FREIDA to identify all categorical pediatric residency programs in the United States. We noted the presence of information programs reported in each FREIDA data field. We compared information available on the program website for consistency with the information in FREIDA and additionally searched for current resident information and any description of the qualities of applicants/residents desired on the program website. Results Two hundred and eleven pediatric residency programs were included in FREIDA. Approximately 25% of programs did not include basic information such as number of first year residents, salary, work hours, or consideration of applicants requiring work visas. Over half of programs did not report minimum licensing examination scores required for interview consideration. Discrepancies between information on program websites and FREIDA related to work visas occurred in 6-8% of programs. While 88% of program websites included information on current residents, only 17% included any description of the applicant attributes sought by the program. Conclusions Many pediatric residency programs do not provide much of the information that applicants need to help determine if a program is a good fit or whether their application is competitive.

Birthweight and serum uric acid in American adolescents.

Elevated serum uric acid is associated with hypertension and chronic kidney disease. We evaluated the relationship between birthweight and uric acid in a nationally representative sample of 5390 US adolescents aged 12-15 in the National Health and Nutrition Examination Survey from 1999 to 2012. There was an inverse association between birthweight and uric acid after adjustment for sex, age, race, obesity, and dietary sodium intake. Each 1 kg increase in birthweight was associated with decreased uric acid by 0.11 mg/dL (95% CI: -0.16 to -0.06; model R2  = 0.32). This relationship was stronger in adolescents with elevated blood pressure (ß = -0.25; 95% CI: -0.44 to -0.06; R2  = 0.50) but persisted in adolescents with normal blood pressure (ß = -0.10; 95% CI: -0.15 to -0.05; R2  = 0.31). In conclusion, lower birthweight is associated with higher uric acid in US adolescents. These findings may support the hypothesis that reduced nephron number is associated with elevated uric acid.

Veno-Venous Extracorporeal Membrane Oxygenation for Continuous Renal Replacement in a Neonate with Propionic Acidemia.

The usual indications for extra corporeal membrane oxygenation (ECMO) are for respiratory or cardiac failure. Although continuous renal replacement therapy (CRRT) is frequently used when patients are on ECMO, the need for CRRT as the primary indication for ECMO is rare. A case of a neonate placed onto veno-venous ECMO for the use of CRRT to treat hyperammonemia from propionic acidemia is presented.

Recognition and reporting of AKI in very low birth weight infants.

BACKGROUND AND OBJECTIVES: AKI is associated with both increased short-term morbidity and mortality and greater long-term risk for CKD. This study determined the prevalence of AKI among very low birth weight infants using a modern study definition, evaluated the frequency of AKI diagnosis reporting in the discharge summary, and determined whether infants were referred to a pediatric nephrologist for AKI follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Records of very low birth weight infants admitted to a level IV neonatal intensive care unit from 2008 to 2011 were reviewed. AKI was classified using the Kidney Disease: Improving Global Outcomes definition modified to include only serum creatinine. RESULTS: AKI occurred in 39.8% of 455 infants; 75 (16.5%) infants experienced multiple episodes of AKI, and 8 (2%) infants were discharged with an abnormal last creatinine. Updated clinical risk index for babies score >10 (odds ratio, 12.9; 95% confidence interval, 7.8 to 21.4) and gestational age <28 weeks (odds ratio, 10.6; 95% confidence interval, 6.8 to 16.7) were strongly associated with AKI in univariate analyses. AKI was associated with increased mortality (odds ratio, 4.0; 95% confidence interval, 1.4 to 11.5) and length of stay (11.7 hospital days; 95% confidence interval, 5.1 to 18.4), even after accounting for gestational age, birth weight, and updated clinical risk index for babies score. AKI was recorded in the discharge summary for only 13.5% of AKI survivors. No infants were referred to a nephrologist for AKI follow-up. CONCLUSIONS: AKI occurred in 40% of very low birth weight infants and was concentrated in the most premature and severely ill infants. One in six infants experienced multiple episodes of AKI, and a small number of infants was discharged with an elevated serum creatinine. Reporting a history of AKI in the discharge summary occurred infrequently, and referral to a nephrologist for AKI follow-up did not occur, highlighting areas for quality improvement.

Nephrotoxic medication exposure in very low birth weight infants.

OBJECTIVE: To quantify exposure to potentially nephrotoxic medications among very low birth weight (VLBW) infants and determine the relationship of nephrotoxic medication exposure to acute kidney injury (AKI) in this vulnerable population. METHODS: We reviewed 107 VLBW infants who survived to discharge from April 2011 to March 2012 and measured exposure to the following nephrotoxic medications: acyclovir, amikacin, amphotericin B, gentamicin, ibuprofen, indomethacin, iohexol, tobramycin and vancomycin. Acute kidney injury was determined by the KDIGO guidelines. RESULTS: Exposure to ≥ 1 nephrotoxic medication occurred in 87% of infants. The most common exposures were gentamicin (86%), indomethacin (43%) and vancomycin (25%). There was an inverse linear relationship between birth weight and nephrotoxic medications received per day (R(2) = 0.169, p < 0.001). Infants with AKI received more nephrotoxic medications per day than those who did not (0.24 versus 0.15; p = 0.003). CONCLUSIONS: VLBW infants are frequently exposed to nephrotoxic medications, receiving approximately two weeks of nephrotoxic medications before discharge or 1 for every 6 d of hospitalization. The greatest exposure occurred among the smallest, most immature infants and those who experienced AKI.