Kidney, Heart Disease, and Diabetes

Polycystic kidney disease

Lisa Guay-Woodford, MD, is an internationally recognized expert in polycystic kidney disease. Her major research effort focuses on identifying the genetic factors involved in the pathogenesis of autosomal recessive polycystic kidney disease (ARPKD). This work has two components: (1) IDENTIFICATION OF disease genes and (2) complex trait analyses to identify candidate modifier genes. As part of the International ARPKD Consortium, her group cloned PKHD1, the major gene involved in human ARPKD. In addition, she characterized two distinct murine models, cpk and bpk, in which the disease phenotype closely resembles human ARPKD and identified the genes, Cys1 and Bicc1, disrupted in each model, respectively. Her current efforts are centered on characterizing the functional roles of these genes and their protein products in normal development and disease pathogenesis.

Clinical Aspects of Pediatric Kidney Disease  

Hans Pohl, MD, (Division of Urology) is interested in the pathogenesis of renal injury from urinary obstruction and urinary tract infection. Dr. Pohl is leading several clinical research trials: (1) RIVUR (Randomized Intervention for Vesicoureteral Reflux, (2) CUTIE (Careful Urinary Tract Infection Evaluation, (3) STARRS (Steroids to Reduce Renal Scarring), (4) Biomarkers (Biomarkers in UTI Evaluation), and (5) GENUSCIS (Personalized GENitoUrinary Health Care: A Longitudinal Study of the Urine Microbiome after Spinal Cord Injury).

These studies focus on understanding the efficacy and long-term side effects of antibiotics used to prevent UTI in children with vesicoureteral reflux (VUR), the incidence of recurrent UTI in children at risk for renal scars, the incidence of bacterial resistance in patients on antibiotic prophylaxis, the risk for progressive renal damage in children with and without VUR who present with UTI, the efficacy of steroids as an adjunct to standard anti-microbial treatment of UTI, the role of biomarkers to assess severity of UTI and the efficacy of microbiome assessment of acute UTI in patients with neurologically abnormal bladders.

Dr. Pohl is also interested in obstructive uropathy, or the study of how obstruction causes renal injury. He seeks to ultize proteomic assessment of urine to improve our understanding of the regulatory framework and molecular response of the infant kidney in the face of obstruction.

Yetrib Hathout, PhD, Eric Hoffman, PhD, and Kanneboyina Nagaraju, DVM, PhD, have received a NIH U54 pediatric pharmacology grant to look at kidney toxicity that may result from long-term systemic treatment with morpholino anti-sense drugs. This very competitive award, one of only four in the U.S., was done in partnership with the Center for Translational Research (John van den Anker, MD, PhD, and Ed Connor, MD). The Center’s effort will focus both on dose-optimization of drug delivery using rodent models, and kidney toxicity biomarkers.

Drs. Hoffman and Hathout also collaborate with Dr. Dominik Rao at the George Washington University on the genetics and pre-clinical symptoms of chronic kidney disease due  to the ApoL1 risk factor seen in African Americans.

Faculty with interests in kidney disease include:

Polycystic kidney disease
Genitourinary infection and obstructive kidney disease
Drug- and genotype-associated kidney toxicity