SUMMARY
The research interests of Karl A. Nath, M.D., center on mechanisms of injury and adaptation to injury in the kidney and in the vasculature. Dr. Nath's National Institutes of Health (NIH)-funded laboratory uses rodent models of chronic kidney disease (CKD), acute kidney injury (AKI) and the dialysis arteriovenous fistula (AVF).
Dr. Nath explores the basis for the protective effects of HO-1, and these include, among others:
- Reducing heme — a prooxidant, proinflammatory and proapoptotic species.
- Generating anti-inflammatory bile pigments.
- Producing antioxidant, iron-binding proteins such as ferritin.
Currently, Dr. Nath is focused on understanding the mechanisms of AKI and mechanisms underlying failure of AVF maturation and function.
Dr. Nath's earlier work demonstrated the benefits of bicarbonate supplementation in CKD. He also showed the protective effects of the inducible antioxidant enzyme, heme oxygenase-1 (HO-1), in AKI and other states of kidney injury, as well as in the rodent models of the AVF.
Focus areas
- Heme-mediated mitochondrial injury, senescence and acute kidney injury. Dr. Nath is the recipient of an NIH R01 grant that funds research around senescence, referring to the state where aging cells can no longer replicate. Dr. Nath's initial studies demonstrate that senescence pathobiology is evident within 24 hours following the induction of heme protein-mediated AKI and is mediated through the upregulation of the cyclin-dependent kinase inhibitor p16. Dr. Nath and his colleagues demonstrate that heme itself upregulates p16 gene expression. Heme also promotes the appearance of a senescence-associated secretory phenotype (SASP), a phenotype commonly displayed by senescent cells.
- Appearance of senescence in rodent AVF models. Dr. Nath's group created murine models of AVF in the setting of CKD that demonstrate features of senescence within one week of AVF creation. The investigators observed features characterized by upregulation of the cyclin dependent kinase inhibitors p16 and p21, increased senescence-associated β-galactosidase activity, and a senescence-associated secretory phenotype (SASP). Dr. Nash has studies currently underway to test whether senolytics or similar compounds that interrupt the appearance of senescence may exert beneficial effects on AVF maturation and function.
- Cardiac effects of a hemodialysis fistula or graft. In collaboration with cardiologists at Mayo Clinic, Dr. Nath studies the cardiac effects of dialysis vascular shunts. They also mark the level of cardiac dysfunction at which the creation of dialysis shunts may increase the risk of heart failure. Additionally, these studies examine the extent to which cardiac dysfunction influences AVF maturation.
Significance to patient care
Dr. Nath seeks to uncover new ways to treat acute kidney injury. He also studies a type of acute kidney injury caused by heme proteins such myoglobin, known as rhabdomyolysis, or hemoglobin, known as hemolysis.
Dr. Nath is finding new therapies that may promote maturation and function of dialysis arteriovenous fistulas (ATFs).
Professional highlights
- Editor-in-chief, Mayo Clinic Proceedings, 2017-present.
- Bywaters Award for Scientific Excellence in the Study of Acute Kidney Injury, International Society of Nephrology, 2020.
- Robert Joseph Patnode Professor of Nephrology, Mayo Clinic, 2017.
- Emeritus editor-in-chief, Journal of the American Society of Nephrology, 2013-2017.
- Merit Award, National Institutes of Health, 2007-2012.
- Distinguished Alumnus Career Achievement Award, University of Minnesota, 2006.
- Chair, Pathology A-Pathobiology of Kidney Disease Study Sections, National Institutes of Health, 2003-2005.
- Member, Association of American Physicians, 1999.
- Member, American Society of Clinical Investigation, 1995.
- Most distinguished graduate, University of Edinburgh Medical School, Edinburgh, U.K., 1978.