The Division of Renal Medicine offers outstanding research opportunities in both basic and clinical/translational sciences research that is conducted in a collaborative environment.
Basic Science Research
Basic science research is weighted in three areas:
- Ion, water, and urea transport
- Mechanisms of cell growth and atrophy
- Signal transduction
Clinical Research
- Hypertension
- Human neurophysiology
- Disease disparities and outcomes
- Vascular calcification
Projects are led by renal medicine faculty who are experts in their respective fields, most of whom are supported by the NIH. The division also has a NIH Training Grant to support MD and PhD fellows who are interested in developing strong research skills for future academic careers and an R25 to support undergraduate students who are interested in a summer research experience. The overall goal of our research programs are to teach young investigators to apply modern research techniques to answer questions related to the causes and consequences of kidney disease and to develop new ways to treat these conditions.
Specific Areas of Research
Ion, Water, and Urea Transport
The urine concentrating mechanism is important for normal homeostasis. Excretion and retention of water and a number of solutes are critical for normal renal physiology. Drs. Jeff Sands and Janet Klein have identified four isoforms of the urea transporter, and are investigating their physiologic functions. The regulation of water via the aquaporin water transporters is being studied by Drs. Sands, Klein, and Susan Wall. Dr. Wall has also identified Pendrin as a chloride channel and utilizes genetically modified mice to study its functions. Drs. Hui Cai and Robert Hoover study the regulation of the sodium-potassium-chloride cotransporter in various models of hypertension.
Mechanism of Cell Growth and Atrophy
In healthy cells, growth is regulated in part by the balance between protein synthesis and degradation. Diabetes, acidosis and other conditions cause excessive renal cell growth which can lead to kidney failure. Dr. Harold Franch investigates the basis of abnormal cell growth in the kidney which includes decreased lysosomal proteolysis. Other complications of diabetes and end-stage kidney disease include muscle atrophy, which results largely from excessive protein degradation. James Bailey and Xiaonan Wang use biochemical and molecular biological techniques to study the mechanisms leading to increased proteolysis by the ubiquitin-proteasome, autophagy and caspase-3 systems.
Signal Transduction
The extracellular milieu regulates many intracellular functions by initiating cell signaling cascades. In the Renal Division, several faculty incorporate cell signaling into their research programs. Drs. Price, Wang and Franch examine the role of phosphoinositol 3-kinase/Akt/Foxo and other signaling pathways in the regulation of the genes involved in the ubiquitin-proteasome and lysosomal proteolytic systems in kidney and muscle. They also investigate how calcineurin impacts muscle protein metabolism.
Drs. Sands and Klein are studying how protein kinases (e.g., Protein kinase A, protein kinase C and AMP Kinase) regulate urea transport. Drs. Hoover and Cai investigate the role of Wnt signaling in chloride transport by angiotensin II, aldosterone and other hormones.
Many of these investigators collaborate with Dr. Eaton who also studies renal mechanisms of controlling total body salt and water balance and the role of renal ion channels in hypertension.
Hypertension and Other Areas of Clinical Research
Clinical-epidemiologic studies that involve testing hypertensive African-American patients to identify whether they are in the “salt-sensitive” category, whether there are differences in the expression of candidate genes that affect the severity of hypertension in Caucasian compared to African-American patients, and building a registry of patients with polycystic kidney disease to determine if progression of renal failure can be linked to clinical characteristics or variations in genetic factors are areas of interest of Drs. Janice Lea and Frederic Rahbari. In particular, Dr. Rhabari utilizes iothalamate renal clearance and magnetic resonance determination of renal volume, cyst volume and renal blood flow in studies of autosomal dominant polycystic kidney disease (ADPKD). Studies also involve careful clinical characterization of patients with low renin hypertension, salt sensitivity and those at risk for primary hyperaldosteronism in conjunction with careful genotyping of their genetic background.
In other clinical research areas, Dr. Jeanie Park investigates derangements of neurovascular control in patients at high cardiovascular risk, particularly those with hypertension, chronic kidney disease (CKD), and stress disorders such as post-traumatic stress disorder (PTSD).
Dr. Charles O’Neill studies the underlying causes of increased vascular calcification in patients with CKD.
Epidemiology/Outcomes Research
Dr. Plantinga investigates the sociodemographic and geographic determinants of quality of care among patients with chronic kidney disease (CKD), end-stage renal disease (ESRD), transplant and geriatric patients.
Dr. Pastan, in collaboration with Dr. Patzer in transplant surgery, studies racial disparities in access to renal transplantation.
Vascular Disease
Dr. Charles O’Neill performs grant-supported basic research on causes and potential therapies for vascular calcification using various animal models of calcification and calcification reversal. The focus of this research is preventative therapies based on pyrophosphate analogs and enzymes related to pyrophosphate metabolism and elucidation of potential mechanisms for reversal of calcifications. This basic research is complemented by a large clinical research program using breast arterial calcification on mammograms as a marker of medial arterial calcification in order to determine risk factors for prevalence and progression. Calcification of renal and intracerebral arteries in CKD are also being studied through imaging and histology. Most of this research is and has been performed together with clinical nephrology fellows. Specific ongoing projects on breast arterial calcification include correlation with pyrophosphate metabolism, progression or regression after renal transplantation, correlation with mineral metabolism, the role of acidosis and alkalosis in ESRD, and development of an automated measurement tool in collaboration with researchers in the Radiology Department.
Autosomal Dominant Polycystic Disease (ADPKD)
Frederic Rahbari Oskoui, MD (Research)
The Division of Renal Medicine at Emory School of Medicine has been at the leading edge of ADPKD research in the world, for the past 2 decades. ADPKD (Autosomal Dominant Polycystic Disease) is the fourth most common cause of End Stage Renal Disease in adults in the United States.
The rich history of the Emory Polycystic Kidney Disease goes back to 1998, when Dr. Arlene Chapman started the program. Many former fellows, including Dr. Frederic Rahbari-Oskoui, the current director of the program since 2015) contributed to the expansion and success of this program, which became an integral part of landmark studies such as The CRISP, the Emory PKD cohort study, the 6 iteration of Tolvaptan trails in ADPKD, the HALT-PKD trials, the metabolomic study in ADPKD, the urinary exosome study in ADPKD and most recently The Tesevatinib in ADPKD trial, THE STAGE-PKD trial (Venglustat) in ADPKD and the FALCON (bardoxolone trial).
An orphan disease, ADPKD was previously a little studied disease with no treatment options. Since then it has been well-characterized and better understood, in part, by the contributions of the Emory investigators invested in understanding the disorder and treating the patients and families affected by it.
The Consortium for Radiologic Imaging Studies of PKD (CRISP) began in 1999 and has been consistently funded by the National Institutes of Health (NIH/NIDDK) for more than 20 years. A multi-generational and dedicated cohort of patients has continued their participation in this longitudinal study of ADPKD. Because of our unique expertise in this genetic disorder, many of these families continue to receive clinical care through at the Emory Clinic. By validating Total Kidney volume as a marker of disease progression in ADPKD, the CRISP studies have directly impacted the funding for new interventions (pharmaceuticals or dietary) since 2006. The number of trials in ADPKD increased form 1 to more than 20 after this important development. The CRISP studies also lead to the development by the Mayo ADPKD classification tool which is a unique tool (for any type of kidney disease) to estimate the time of inset of ESRD in ADPKD patients with a high level of confidence. This groundbreaking tool, intended to optimize the selection of subjects for clinical trial participation, uses total kidney volume (TKV) to classify patients into five groups based on predicted disease progression.
In 2018, Tolvaptan (Jynarque), the first and only disease-modifying agent for ADPKD was approved by the FDA for use in the US market. Emory served as one of the largest global sites for the six clinical trials in the development of this new drug from 2005 to 2018.
The Polycystic Disease Center of Excellence continues to participate in global clinical trials, NIH studies, and patient care for those affected by ADPKD.