Nephrology Research

The research program within Boston Children's Hospital's Division of Nephrology conducts both basic and clinical research in transplantation biology, kidney development, nephrotic syndrome, and autosomal recessive polycystic disease of the kidney. The heads of our key laboratories also hold faculty appointments at Harvard Medical School.

Recognizing that more than half of children with kidney failure have developmental anomalies, the division has assembled a very large developmental and regenerative biology team. We also have created a pharmacogenomics group to take advantage of the remarkable breakthroughs of modern genomics and customize treatments to each child.

Current nephrology research projects

Genetic testing for nephrotic syndrome and FSGS

Our researchers, together with collaborators, have identified multiple genetic mutations associated with segmental glomerulosclerosis (FSGS), a devastating form of nephrotic syndrome that is the second leading cause of kidney failure in children. Based on this research, we now offer a diagnostic test panel for nephrotic syndrome and FSGS that covers more than two dozen genes.

Our team is also using the genetic information to develop better treatments for FSGS and nephrotic syndrome. For example, a study in the lab of our division chief Friedhelm Hildebrandt, MD, identified genetic mutations that involve Coenzyme Q-10. A clinical trial led by Ankana Daga, MBBS, will give Coenzyme Q-10 to children with nephrotic syndrome to see if it improves their disease course.

Understanding kidney self-repair

End-stage kidney disease often begins with injury to podocytes, highly specialized cells that intermingle with the capillaries and filter the blood, maintaining the proper water and salt balance. The lab of Jordan Kreidberg, MD, PhD, has been trying to understand how kidneys and podocytes naturally maintain themselves. The team recently identified a master genetic program and a key regulator called WT-1 that appears to orchestrate podocytes’ innate injury-repair response. Kreidberg and his colleagues continue to study WT1 and other genetic factors in podocyte injury to better understand the repair process and identify potential treatments for FSGS and kidney failure due to diabetes or hypertension.

Improving outcomes following kidney transplantation

Dr. David Briscoe and faculty within the Transplant Research Program are conducting a variety of studies to improve the longevity of transplanted organs and better identify patients at risk for complications. The Briscoe Lab studies the processes of inflammation resolution and the discovery of receptor ligand interactions that both promote and inhibit alloimmunity and the rejection process. Research studies are in three broad areas including:

  1. how events within the intragraft microenvironment promote, sustain or inhibit T cell activation and allorecognition
  2. how discrete signals and molecular interactions in select populations of T cells promote immunoregulation
  3. the application of these discoveries into the development of biomarkers and new therapeutics to transform clinical care and improve outcomes following transplantation

Dr. Soumitro Pal and members of his laboratory study molecular mechanisms of cancer growth in patients following organ transplantation using in vitro cell culture models as well as a sophisticated murine model. Dr. Pal's research also aims to identify molecular targets and novel therapeutics for the treatments of renal inflammation and renal cancer.

Dr. Johannes Wedel uses bioinformatic tools and sophisticated immunological techniques to study the identification of novel cell types and signaling pathways that regulate T cell-dependent immune responses following transplantation.

Kidney stone genetics and prevention

Recent research by Friedhelm Hildebrandt, MD, found that a surprising 21 percent of children with kidney stones have a causative single-gene mutation. Knowing the mutation can often change therapy. For example, certain stone-causing mutations have been associated with other treatable medical complications that clinicians can screen for, such as eye problems or hearing loss.

Michelle Baum, MD, co-director of the Kidney Stone Program, hopes that care for kidney stone disease will one day be focused on preventing stone formation, rather dealing with its consequences. She is helping to launch clinical trials of new medications to treat primary hyperoxaluria (PH), one of the rarest, most devastating causes of kidney stones as well as other organ complications. For many years, PH could only be treated by kidney-liver transplant. Dr. Baum is a primary investigator in a multicenter clinical study that aims to correct the genetic error in metabolism that causes PH using RNA inhibitor therapy.