Nephrology

Research Activities

Clinical Research

The Division of Pediatric Nephrology has ongoing collaborative research studies on the use of growth hormone in children with chronic renal failure, on therapy for the nephrotic syndrome, and on the use of antihypertensive medications in children. The division is also part of the North American Pediatric Renal Trials and Collaborative Studies, an important research and data collection program for children with chronic renal failure, dialysis, or renal transplantation.

Laboratory and Translational Research

The Pediatric Hypertension Outcomes Measures Study The Pediatric Hypertension Outcomes Measures Study is a transformation of child health research at New York/Connecticut (NYCONN) CTSA sites including Einstein/Montefiore, Columbia University, University of Rochester, Weill Medical Center of Cornell University and Yale University School of Medicine, into an effective multidisciplinary translational investigative team poised to enhance the health care of children both regionally and nationally. A network of basic and clinical investigators will share data and resources to enhance clinical and translational research in pediatric hypertension and serve as a model for CTSAs nationwide. This multicenter collaboration is aimed at identifying the epidemiologic, molecular and genetic mechanisms of pediatric hypertension and the precursors of adult cardiovascular disease.

Morphologic biomarkers of response to therapy in nephrotic syndrome Currently we have no established biomarkers in clinical use that will reasonably predict which patients with nephrotic syndrome (NS) are going to respond to treatment. This is of concern, because the therapies that are used to treat NS are not innocuous and can have adverse effects on the patients. Electron microscopy (EM) images of minimal change NS reveal diffuse podocyte foot process effacement (widening and disappearance of the foot-like podocyte extensions) while, in focal segmental glomerulosclerosis (FSGS) involved and "normal appearing" glomeruli have more variable effacement of podocyte foot processes. We therefore are in the process of examining the association between the degree of podocyte foot process effacement and immunosuppressive treatment outcomes (response vs. partial response/no-response) in collaboration with NIH-sponsored Nephrotic Syndrome Study Network (NEPTUNE) Longitudinal Cohort study.

Association of apolipoprotein-1 (APOL1) genetic variants with renal disease progression and cardiovascular morbidity in African Americans Up to 48–63% of children with early stages of Chronic Kidney Disease (CKD) present with hypertension (HTN). In addition to being common, HTN is associated with a greater rate of decline in kidney function and known risk of development of end-stage kidney disease (ESKD). NIH-sponsored study of children with CKD (CKiDS) showed that 17% of participants had uncontrolled systolic HTN (BP >95th percentile) and 7% had pre-HTN (BP 90–95th percentile) making overall prevalence of systolic HTN at 53%. APOL1 genetic variants have been associated with the increased susceptibility to focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy, and hypertension-attributed end-stage kidney disease (H-ESKD) observed in African Americans. However, whether APOL1 risk alleles G1 and G2 are associated with progression of renal disease (decline in iGFR and worsening of proteinuria) and cardiovascular morbidity (LVH, HTN) in children of African American ancestry has not been studied. We are currently studying this association in collaboration with CKiDS and NIH.

Stem Cell Therapy for Acute Kidney Injury This project combines the knowledge of basic stem cell biology with translational research to investigate the potential of using stem cells to treat acute kidney injury. We induce hematopoietic stem and progenitor cells to differentiate into renal-like cells in the laboratory and test the therapeutic potential of the cells in mouse models. The future goal is to develop safe and effective treatments for human kidney disease. (NIH/NIDDK, R01DK083411)

Role of Autophagy in Kidney Tubular Atrophy Urinary tract obstruction during kidney development can result in kidney malformations, kidney tubular atrophy and renal failure. The aim of this study is to test whether autophagy (self-eating of the cell) plays a role in obstruction-induced tubular atrophy in mouse models. Understanding the mechanism of tubular atrophy will guide our future development of strategies to prevent and/or slow down the progression of chronic kidney disease. (March of Dimes Research Grant, 6-FY11-311)

Phenotype-genotype Correlations in Congenital Aanomalies of the Kidney and Urinary Tract (CAKUT) Congenital anomalies of the kidney and urinary tract (CAKUT) is responsible for up to 30-40% of pediatric end stage renal disease, and accounts for more than 20% of overall birth defects. We are studying the entire spectrum of CAKUT, including vesicoureteral reflux (VUR), ureteropelvic junction obstruction (UPJO), hypoplasia/dysplasia, duplicated collecting systems and/or a combination of the above anomalies. There is strong evidence that there is a genetic component to human CAKUT, but the genetic basis still remains undetermined. Working with the pediatric urologists here at the Children’s Hospital of New York Presbyterian Hospital and with researchers in the division of adult nephrology, we have collected one of the largest databases of patients with CAKUT. We are currently conducting genome-wide studies on our cohort of patients with the CAKUT phenotypes in order to gain insight into phenotype-genotype correlations, prognostic factors and the possibility of developing better less invasive diagnostic procedures.