The Mayo Clinic Division of Nephrology and Hypertension Research carries out a broad scope of multidisciplinary investigations, encompassing most areas in the field. Research includes investigations and collaborations to improve understanding, diagnosis, prevention and treatment in multiple areas of kidney health and disease.
Acute kidney injury
Kianoush B. Kashani, M.D., M.S., develops methods to predict and prevent acute kidney injury, including early biomarkers and clinical and electronic models. He also focuses on managing acute kidney injury, including through the use of artificial intelligence.
Dr. Kashani's research is aimed at finding appropriate paths to manage fluid and vasopressor therapy among patients who have a high risk of acute kidney injury, as well as at developing and validating clinical and automated models to assist clinicians in the management of nephrotoxins. His other areas of interest include acid-base balance and electrolytes, renal replacement therapies, fluid management, point-of-care ultrasonography, and education.
Aging of the kidney
Andrew D. Rule, M.D., leads the department's research on aging of the kidney. His Aging Kidney Anatomy Study uses kidney biopsies and CT scans to determine the microstructural and macrostructural changes that occur in the human kidney with aging and early disease.
Distinguishing age-related from disease-related changes in the kidney will help better classify patients at risk of progression to kidney failure. It will also help researchers better understand the aging process to develop novel therapies that prevent or delay aging in the kidney.
Calcium and phosphate homeostasis
Research on calcium and phosphate homeostasis in the Division of Nephrology and Hypertension is led by Rajiv Kumar, M.D., and includes projects on:
- Arteriovenous fistulas
- Clinical bone mineral physiology in health and disease
- Mechanism of action 1α,25-dihydroxyvitamin D in muscle, bone and the central nervous system
- Regulation of serum and whole-body phosphate by novel phosphate-regulating hormones
- Urinary stone disease
Dr. Kumar's work is relevant to the pathogenesis and treatment of bone disease seen in patients with renal failure, osteoporosis and hypophosphatemia.
John J. Dillon, M.D., leads dialysis research in the Mayo Clinic Division of Nephrology and Hypertension. Topics of research focus include:
- Optimal treatment of end-stage renal failure, including management of bone disease, anemia, and dialysis prescription
- Cardiovascular disease in end-stage renal failure
- Cellular mechanisms of chronic renal injury and the pathogenesis of renal fibrosis
- Find a list of the most recent dialysis-related publications from Mayo Clinic on PubMed.
Epigenetics in polycystic kidney disease (PKD)
Xiaogang Li, Ph.D., focuses his research on molecular mechanisms associated with cyst formation, with an emphasis on epigenetics, inflammation and crosstalk between the two in PKD. This research will help determine whether inherited PKD gene mutations in patients favor the development of epigenetic and inflammatory changes, and will increase the understanding of PKD pathophysiology to identify novel epigenetic targets for PKD treatment.
Dr. Li's laboratory also provides consulting and other services that use epigenetic techniques to generate molecular data from biospecimens from patients with kidney diseases and animal models.
Lilach O. Lerman, M.D., Ph.D., studies the pathophysiology of renovascular disease, high blood pressure (hypertension) and cardiac adaptation. In particular, Dr. Lerman's lab is focused on finding better ways to treat the narrowing of arteries that carry blood to the kidneys (renal artery stenosis), which can cause hypertension.
One project in Dr. Lerman's lab explores how MRI can be used to asses renal and cardiac hemodynamics and to characterize magnetization transfer imaging in renal stenosis. Other projects in the lab, focused on kidney regeneration, are described below.
Inherited kidney diseases (other than PKD)
Peter C. Harris, Ph.D., is pursuing genetic and cellular studies of Meckel-Gruber syndrome after identification of the MKS3 gene. Meckel-Gruber syndrome, also called Meckel syndrome, causes numerous and often fatal abnormalities, including fluid-filled cysts in the kidneys.
Kidney regeneration studies in the Mayo Clinic Division of Nephrology and Hypertension Research are led by:
- Alfonso Eirin Massat, M.D.
- Sandra M. Herrmann, M.D.
- LaTonya J. Hickson, M.D.
- Lilach O. Lerman, M.D., Ph.D.
- Sanjay Misra, M.D.
- Roman Thaler, Ph.D.
- Andre J. van Wijnen, Ph.D.
Dysfunctional mesenchymal stem cells from patients with hypertensive kidney disease show increased release of enriched extracellular vesicles (EVs) after hypoxia preconditioning.
Regeneration and hypertensive kidney disease: Sandra M. Herrmann, M.D.
Dr. Herrmann's research involves applying mesenchymal cell therapy in preclinical models of hypertensive kidney disease. Her research is aimed toward translation to patients with chronic kidney disease in the setting of hypertension, occlusive renovascular disease or both.
Dr. Herrmann is interested in preparing mesenchymal stem cells in a reduced oxygen supply (hypoxia preconditioning) to optimize their function in patients with chronic kidney disease. She is also studying the effects of hypoxia preconditioning on specific hormonal (paracrine) mechanisms of mesenchymal stem cells and their derived extracellular vesicles.
Dr. Herrmann's research goal is to improve the outcomes of patients with chronic kidney disease through innovative research identifying novel regenerative medicine therapies. Such therapies could help with recovery — or at least stabilization — of kidney function to avoid or postpone renal replacement therapies such dialysis or kidney transplantation.
Regeneration in diabetic nephropathy: LaTonya J. Hickson, M.D.
LaTonya J. Hickson, M.D., leads several clinical studies on chronic or end-stage kidney disease in patients with diabetes (diabetic nephropathy).
The goal of Dr. Hickson's research is to test the safety, feasibility and efficacy of mesenchymal stromal cell therapy in individuals with diabetic kidney disease. Her proposed therapy is patient-derived, meaning the cells are taken from the individual patient, processed and given back to the patient at a later date. Dr. Hickson's research team administers the cells directly to the patient's kidney to allow immediate access to the injured organ. A clinical trial delivering these stem cells is currently underway.
In addition, Dr. Hickson has other studies investigating the function of stem cells in individuals with diabetes and interventions that may improve stem cell functionality.
Dr. Hickson's regenerative nephrology research has the potential to minimize injury to the kidneys of people with diabetes and even promote repair. This novel therapy may help delay the progression of kidney failure.
Obesity and stem cell senescence: Lilach O. Lerman, M.D., Ph.D.
Dr. Lerman's Renovascular Disease Laboratory studies obesity-induced mesenchymal stem cell senescence. Her research team uses unique and novel model systems and techniques to study whether and how obesity evokes aging (senescence) in human mesenchymal stem cells, interfering with their capacity to repair injured kidneys.
The team hypothesizes that the impaired function of mesenchymal stem cells is partly mediated by a phenotype shift in extracellular vesicles that drive their paracrine effects. However, this impairment could be reversible upon senolytic pretreatment of mesenchymal stem cells or after weight loss.
Interim findings suggest increase senescence in adipose tissue-derived mesenchymal stem cells obtained from patients with obesity, compared with similar cells from lean patients. This research may uncover novel mechanisms involving impaired cellular repair systems that underlie complications of human obesity.
Dr. Lerman's team hopes to establish a novel strategy to prevent or lessen injurious cellular senescence, thereby boosting endogenous kidney repair capability.
Regeneration, metabolic syndrome (MetS) and renovascular disease: Lilach O. Lerman, M.D., Ph.D.
Dr. Lerman's Renovascular Disease Laboratory studies mesenchymal stem cell-derived microvesicles in MetS and renovascular disease. The research team focuses on MetS — a constellation of cardiovascular risk factors that induces kidney damage and raises the risk of chronic kidney disease, partly by rendering the kidney vulnerable to a reduction of blood flow (ischemia). Indeed, MetS coexisting with renovascular disease is linked to poorer outcomes after revascularization, possibly due to inflammation that characterizes MetS.
However, tools to blunt the renal effects of MetS are yet to be identified, partly due to the lack of translational animal models of MetS and clinically applicable therapeutic tools. To address this unmet need, Dr. Lerman's lab is working to develop and evaluate the capability of a platform to improve kidney viability in a novel swine model of MetS and renovascular disease that the lab recently developed, which closely mimics human pathophysiology and allows translational studies and interventions relevant to human clinical medicine.
Interim findings suggest increased senescence and dysfunction in adipose tissue-derived mesenchymal stem cells obtained from the MetS animal model, as well as in their extracellular vesicles. RNA sequencing and proteomics showed altered expression of mRNA, miRNA and proteins related to inflammation.
This research provides a unique opportunity to assess the feasibility of modifying renal outcomes in MetS and renovascular disease, which will likely contribute toward management strategies for patients with renovascular disease and MetS.
Representative transmission electron microscopy image of cultured swine adipose tissue-derived mesenchymal stem cells. Sections were stacked and aligned, and two mitochondria were reconstructed using 3D reconstruction software. Scale bar=10μm.
Mitochondria, stem cell biology and renal repair: Alfonso Eirin Massat, M.D.
Within Dr. Lerman's lab, Dr. Eirin Massat and colleagues are exploring the fundamental role of mitochondria in modulating stem cell biology and function. His research group also explores the impact of mitochondrial damage in the overall renal repair capacity of stem cells and develops novel therapeutic interventions (mitoprotective drugs). His work contributes to the development of novel therapeutic tools to preserve the regenerative potency of stem cells and their suitability for autologous transplantation in patients.
Stem cells to improve dialysis: Sanjay Misra, M.D.
Dr. Misra's Vascular and Interventional Radiology Translational Research Laboratory is studying the use of stem cells in improving dialysis for patients.
One of the lab's projects assesses the safety of adipose-derived autologous mesenchymal stem cells for reducing the failure of arteriovenous fistulas in hemodialysis. Arteriovenous fistulas are used to access and purify blood during dialysis. They have limited life spans and eventually fail because the blood vessels narrow, causing a decrease in blood flow and poor filtration during dialysis.
Dr. Misra's research team is therefore studying the topical application of stem cells to the vessels used to create the fistula to see if the cells can potentially slow the narrowing process and increase the life spans of the fistulas.
Additionally, Dr. Misra's lab is using a murine model to assess the safety and effect of adipose-derived mesenchymal stem cells in reducing renarrowing of blood vessels (restenosis) after percutaneous transluminal angioplasty (PTA) treatment.
PTA is a noninvasive, first-line treatment for immaturation and failure of hemodialysis access, but restenosis limits its use. Moreover, restenosis not only is important in hemodialysis treatment but also is the common complication for almost all other vascular interventional procedures.
Dr. Misra's team has already used one clinically relevant murine model to transplant adipose-derived mesenchymal stem cells into PTA-treated vessels and observed successful outward remodeling.
This research leverages stem cells' anti-inflammation properties and ability to regulate remodeling, offering the potential of therapeutic value in dialysis and future interventional treatments for vascular restenosis.
Molecular biology of stem cells: Andre J. van Wijnen, Ph.D., and Roman Thaler, Ph.D.
In Dr. van Wijnen's Stem Cell Therapy and Cellular Regeneration Laboratory, Drs. van Wijnen and Thaler study the molecular biology of stem cell function in regenerative therapies. Their research is focused on the molecular mechanisms and cellular processes that support the biological functions of adult stem cells in regenerative cell therapies to treat renovascular diseases. They examine the following specific topics:
- Differences in stem cell properties between patients with different renal and metabolic disorders, including distinctions in the epigenome, transcriptome, secretome and surfactome
- The therapeutic secretome of stem cells, including the molecular cargo of extracellular vesicles secreted from stem cells
- Retention of therapeutic dosing of stem cells subjected to logistic manipulations that affect the metabolic state and viability of stem cells
Mineral metabolism and stone disease
As director of the O'Brien Urology Research Center at Mayo Clinic, John C. Lieske, M.D., is working to identify factors that mediate adhesion of crystals to renal tubules and to understand how subsequent cellular processing of retained crystals results in renal stone formation.
Nelson Leung, M.D., studies kidney diseases caused by monoclonal gammopathy, particularly immunoglobulin light chain amyloidosis, a disease caused by the overproduction of immunoglobulin light chains that form amyloid fibrils. Dr. Leung focuses on improving current diagnostic techniques and redefining response criteria in these patients.
Oxidative stress and renal disease
Karl A. Nath, M.D., leads research on the mechanisms of oxidative stress and renal disease in the Mayo Clinic Division of Nephrology and Hypertension. In particular, Dr. Nath focuses on the inducible antioxidant enzyme heme oxygenase-1 (HO-1) as an adaptive response protects the kidney and vasculature from injury. He also uses approaches based on transgenic models of sickle cell disease to investigate the role of oxidative stress in damaging the kidney and vasculature in sickle cell disease.
Parenchymal and glomerular renal disease
As the director of the Mayo Nephrology Collaborative Group, Fernando C. Fervenza, M.D., Ph.D., leads interventional studies aimed at bringing new bench research discoveries to the bedside treatment of patients with parenchymal or glomerular renal diseases including:
- Membranous nephropathy
- IgA glomerulonephritis
- Focal and segmental glomerulosclerosis
- Lupus nephritis
- Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
Dr. Fervenza's research to improve the understanding of the pathogenic processes involved in some of these diseases is aimed at developing novel agents for more effective treatment.
As a member of the Rare Kidney Stone Consortium Registry, David J. Sas, D.O., focuses on children with idiopathic kidney stone disease or very rare disorders like primary hyperoxaluria, Dent's disease and cystinuria. Dr. Sas is also studying the impact of variations in urinary microbiome in different settings of health and disease.
Polycystic kidney disease (PKD)
As director and associate director, respectively, of the Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Vicente E. Torres, M.D., Ph.D., and Peter C. Harris, Ph.D., translate basic scientific findings into new and better treatments for patients with PKD.
Dr. Torres is focused on the epidemiology, phenotypic characterization, natural history and clinical management of PKD and related diseases. He has also contributed to the identification of responsible genes and expression and function of the encoded proteins, as well as to preclinical and clinical therapeutic trials.
Dr. Harris' lab uses genetic approaches to investigate molecular events associated with tubule formation, with a focus on polycystic kidney disease and related conditions.
Fouad T. Chebib, M.D., focuses on understanding the underlying molecular mechanisms that lead to cyst formation in PKD and exploring targeted treatment options. His clinical and translational research focuses on optimizing the clinical management of patients with autosomal dominant polycystic kidney disease (ADPKD).
Rare Kidney Stone Consortium Registry
John C. Lieske, M.D., is the director of the Division of Nephrology and Hypertensions' Rare Kidney Stone Consortium Registry. The registry aims to identify as many people as possible with primary hyperoxaluria or Dent's disease around the world, and to collect as much clinical information about these patients as is feasible.
The goals of the registry are to increase understanding about these rare disorders, to provide evidence that can be used to establish patient care guidelines and to provide the basis for future clinical trials.
Dr. Lieske is also evaluating novel methods to treat enteric hyperoxaluria, including the use of probiotics and herbal therapy.
Transplantation research in the Mayo Clinic Division of Nephrology and Hypertension is led by Mireille El Ters, M.D., and Carrie A. Schinstock, M.D.
Dr. El Ters studies the prevention and management of recurrent post-transplantation glomerular diseases as well as the genetic basis for kidney transplantation, with a particular focus on patients with focal segmental glomerulosclerosis.
Dr. Schinstock is focused on developing a therapy for chronic antibody-mediated rejection that leads to transplant failure.
Vesna D. Garovic, M.D., Ph.D., and Tracy L. Weissgerber, Ph.D., lead the division's obstetric nephrology research.
Dr. Garovic is focused on the pathophysiology of preeclampsia and the role that dysregulation of glomerular epithelial cells may play in renal injury and proteinuria in preeclampsia. She also studies the role of epigenetic mechanisms in the regulation of specific signaling pathways that may contribute to impaired immune responses and vascular injuries in women with preeclampsia, both at the time of delivery and postpartum.
Dr. Weissgerber investigates risk factor profiles of women who have had preeclampsia and how these profiles change over time, with the goal of developing effective strategies to prevent hypertension and cardiovascular disease.