On the Frontiers of Kidney Disease Research

A “silent killer”: that’s what kidney disease is called. It strikes one in ten people
in the U.S., but often with few symptoms until later stages in the disease — so
those who have it may not know they are ill.

Kidney disease in the U.S.

• 1 in 10 people in the U.S. have kidney disease (acute or chronic) — over 20 million total.

• African-Americans are more than 3 times as likely as Caucasians to develop kidney failure — and up to 10 times as likely to develop kidney failure due to hypertension.

• Less than 1% is invested in NIH kidney research ($591 million) compared to the annual Medicare cost for all patients with kidney disease ($77 billion). See table below for a comparison of NIH research funding by disease.

March is National Kidney Month, and one important goal is raising public awareness about kidney disease prevention. Another is galvanizing the research community to make inroads in treatment.

The UVA Division of Nephrology has long been recognized for its excellence in patient care, earning a “high-performing” ranking from U.S. News & World Report for several years in a row. It is also at the forefront of basic and translational research in kidney disease —  and with recent infusions of funding from the National Institutes of Health (NIH) and other sources, it is well-positioned to push the frontiers of kidney research in new directions.

During FY 2016, division faculty received new or renewed NIH grants totaling nearly $15 million. Division chief Mark Okusa (right) says he is especially pleased that junior faculty such as Uta Erdbrügger, Amandeep Bajwa, Rahul Sharma and Bert Kinsey (right, below) have been successful in obtaining support. It means, he says, that “we’re succeeding in our mission of training the next generation of investigators in  kidney disease.”

“The success of these young investigators is made possible by the rich research environment at UVA, and by the strong mentorship provided by established NIH-funded investigators in the division, the Center for Immunity, Inflammation & Regenerative Medicine, and throughout the institution,” Okusa remarked.

Below, four Nephrology faculty members discuss their current research.

Amandeep Bajwa, PhD 

I’m currently investigating how modulation of sphingosine receptors on dendritic cells (DCs) can induce them to become regulatory. We recently discovered that the Sphingosine-receptor-modulated DCs have more mitochondria — the “powerhouse” of cells. Over the next few months we plan to test if this increase in mitochondria is responsible for making these cells regulatory.

Regulatory DCs may, in the future, be used as cellular therapy to prevent kidney injury; DC therapy is already approved for many autoimmune diseases. And the findings from our research could one day be used to help transplanted kidneys have better graft function.

Recent publication: Bajwa A, Huang L, Kurmaeva E, Gigliotti JC, Ye H, Miller J, Rosin DL, Lobo PI, Okusa MD. Sphingosine 1-phosphate receptor 3-deficient dendritic cells modulate splenic responses to ischemia-reperfusion injury. Journal of the American Society of Nephrology, 2015 Aug; 18. pii: ASN.2015010095. [Epub ahead of print]. PMID: 26286732.

Gilbert (Bert) Kinsey, PhD, PharmD

During my postdoctoral fellowship in the Division of Nephrology, we realized that immune cells called regulatory T cells (“Tregs”) have the capacity to prevent kidney damage in a mouse model of acute kidney injury (AKI). We found that mice with reduced Treg levels were more susceptible to kidney injury, while those with higher levels were more resistant to it.

In my own lab, we are now developing genetically modified mice with the aim of better understanding the protective function of Tregs.  We think that by boosting the level of Tregs in patients, we may be able to prevent AKI.

AKI occurs in many hospitalized patients and leads to longer hospital stays, increased chances of chronic kidney disease and higher rates of death. So far there have been no drug therapies to prevent or treat AKI. Up to one-third of heart surgery patients develop AKI after surgery, so an urgent clinical need is finding ways to prevent this complication.

We have recently launched a collaboration with colleagues in the Department of Surgery, the Surgical Therapeutic Advancement Center, and the Department of Public Health Sciences to measure Tregs in heart surgery patients in order to test whether those with lower Treg levels are at higher risk of developing AKI. As we study the role of Tregs in human AKI, we hope to develop new ways to help patients with, or at risk for, kidney disease.

Recent publication: Jaworska K, Ratajczak J, Huang L, Whalen K, Yang M, Stevens BK, Kinsey GR. Both PD-1 ligands protect the kidney from ischemia reperfusion injury. Journal of Immunology 2015 Jan 1;194(1):325-33. doi: 10.4049/jimmunol.1400497. 

Rahul Sharma, PhD

My lab studies the pathways that control autoimmune and inflammatory conditions, which are caused by abnormal activation of the immune system due to a variety of factors, including genetic defects, major trauma or infections. Current treatment strategies are often not very effective, or have deleterious side effects.

We have identified critical inherent mechanisms that control abnormal immune activation and inhibit pathways of inflammation. Recently we have generated novel biological reagents which strengthen these anti-inflammatory responses – specifically, by improving the level and function of certain immune cells, including regulatory T-cells (Tregs) and group 2 innate lymphoid cells (ILC2).

Using animal models, we have demonstrated that the use of our novel reagents is protective in autoimmune disease such as type-1 diabetes and lupus nephritis, in which the immune system attacks the pancreas and the kidneys, respectively. The strategy protected kidneys from damage due to type-2 diabetes, as well as from ischemia (loss of blood supply, such as may occur during cardiac surgery) and from toxic anti-cancer drugs. This anti-inflammatory approach has strong therapeutic potential. Encouraged by the findings, we have filed an international patent (PCT/US2014/056767) in cooperation with UVA Licensing and Ventures group. The patent is now published online, and we are currently preparing three manuscripts that will discuss these findings.

Among other NIH-funded studies, we are investigating how inefficient clearance of DNA and other cellular debris after cell death contributes to autoimmunity and inflammation.

Sundararaman Swaminathan, MD

I became interested in the area of iron homeostasis when I was at the University of Arkansas and studying the potentially toxic side effects of MRIs performed with gadolinium-based contrast agents. After joining UVA, I started to investigate the role that iron export –specifically hepcidin, a peptide which reduces iron export – plays in preventing and treating acute kidney injury.

My lab has so far established that hepcidin treatment is highly effective in preventing and treating acute kidney injury, and we have started discussions with stakeholders to translate these findings into the clinical setting. Long-term, our research could lead to establishment of hepcidin as an effective therapy for the prevention and treatment of acute kidney injury.

In our ongoing investigations, we are working to establish the cellular immune mechanisms by which hepcidin mediates protection in acute kidney injury. We will also be testing the effectiveness of novel hepcidin analogues and hepcidin-inducing strategies.

Recent publication: Scindia YS, Dey P, Thirunagari A, Liping H, Rosin D, Floris M, Okusa MD, Swaminathan S. Hepcidin mitigates renal ischemia-reperfusion injury by modulating systemic iron homeostasis. Journal of the American Society of Nephrology 2015; 26: 2800-14. 

nih-research-funding-by-disease (1)


Nephrology chief Mark Okusa, MD: “What is exciting is that we’re succeeding in our mission of training the next generation of investigators.”


Uta Erdbrügger, MD


Amandeep Bajwa, PhD

Copy of Bert-Kinsey-Lab-4a

Bert Kinsey (right) with lab technician Brian Stevens, who has been at UVA for 33 years.

Rahul Sharma, PhD

Sundararaman (“Swami”) Swaminathan, right, with lab members Saleh Mohammad (middle) and Ewa Mandziak (left). Ewa recently had a poster accepted for the all-University “Public Day.”

Dr. Swaminathan

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