Preventing Progression of Kidney Disease

Tarak Srivastava, MD, FASN, is a pediatric nephrologist and researcher at Children’s Mercy Kansas City. He runs a National Institutes of Health (NIH)-funded Nephrology Research Laboratory and is actively involved with various multicenter clinical research studies funded by the NIH. Dr. Srivastava was named as a new member of the American Pediatric Society in 2021 and in January 2023 was elected to the board of the Pediatric Nephrology Research Consortium.

Tell us about your role with the PNRC and what you hope to accomplish as a board member.

I have served as a member and as chair of the PNRC-Protocol Review Committee, member of MWPNC-Industry Engagement Request Sub-committee, and as chair of the ESPN-PNRC Joint Research Program.

Physicians interested in basic laboratory research are ~2% of total physicians. I would like to develop an interest group of fellows, junior and senior faculty interested in basic laboratory research within PNRC as we continue to grow and expand. We need this interest group as we consider translational research and industry partnerships in the future.

We have initiated a research collaboration with our European colleagues. It may be a good time to consider building a niche in the area of collaborative research across continents. I believe mentoring and sponsoring the growth of young individuals and expanding our research collaboration under PNRC will help make a substantial impact.

Why did you choose to focus your career on nephrology research?

It was in April of 1990 when as a first-year pediatric resident, I encountered a young child with reflux nephropathy and severe CKD who lived in a small village in Maharashtra, India. There was no available dialysis or transplantation at the time in India for children with severe CKD, and all we had was conservative and palliative care to offer. There was nothing more we could do to help that child live. That was the trigger which chose this path for me. I have focused my research on finding ways to delay the progression of chronic kidney disease in children so that they may not require dialysis or transplantation down the road.

What are your specific areas of research focus?

We have three areas of interest in the laboratory, namely, understanding the mechanistic basis of hyperfiltration-mediated injury to mitigate the progression of chronic kidney disease, understanding the mechanistic basis for susceptibility to chronic kidney disease, and understanding the immunological dysfunction in nephrotic syndrome. My clinical research is focused on children with glomerular disease, osteoporosis and kidney stones.

What prompted you to study these areas? What problem are you trying to solve?

We have identified the mechanism underlying fluid flow shear stress injury in hyperfiltration leading to progression of chronic kidney disease. In our most recent publication, we have shown how drugs can mitigate the progression of chronic kidney injury in animal models. These drugs will need to be taken into human clinical trials in the future. With my research projects and clinical trials in nephrotic syndrome, I have learned that we need to go back-and-forth between bench side research using animals and in vitro techniques and bedside research with clinical trials to achieve the greatest progress.

Your work on prostanoid receptors was recently published in the FASB Journal, the Journal of the Federation of American Societies for Experimental Biology. What was the focus and key findings of that publication?

The key focus of the FASEB publication was to show how blocking the prostanoid receptor EP2, in conjunction with activating the prostanoid receptor EP4 can significantly mitigate the progression of chronic kidney disease from hyperfiltration-mediated injury. The drugs have now been shown to be safe and efficacious in animal models and will need to be studied in humans.

What do you see as the biggest opportunity for pediatric nephrology laboratory research in the next 3-5 years?

With the recent advances in genomics, proteomics and metabolomics, we as a community in pediatric nephrology have developed a better understanding of many conditions that are commonly seen in pediatric nephrology. Many of these diseases now have therapeutic targets. I foresee novel treatments coming out of this research in the next three to five years that will be helpful for these children.