The Division of Nephrology offers diverse opportunities for Clinical Investigation. Several members of the faculty are Principal Investigator or Collaborating Investigator for large clinical trials. Faculty are also involved as Investigators or Co-investigators for local sites for multicenter pharmaceutical sponsored phase 3 and phase 4 clinical trials. Some of the current clinical studies or clinical research projects include:
Proteomics & Biomarker Discovery in human kidney diseases (Dr. Arthur):
Biomarkers are proteins that can be used to diagnose diseases, predict prognosis or project a patient's response to therapy. A rapidly developing area of translational research is biomarker discovery. We are developing and using new proteomic and informatic technologies to identify patterns of biomarker proteins in urine that can predict diagnosis and prognosis of patients with renal diseases. An example of biomarker discovery is our recent identification of a pattern of proteins that can distinguish between patients with four glomerular diseases: FSGS, membranous nephropathy, lupus nephritis and diabetic nephropathy. Renal glomerular diseases are a leading cause of end-stage renal disease. This discovery may lead to tests that can replace the kidney biopsy as a diagnostic technique. Using a diagnostic test instead of kidney biopsy will enable doctors to diagnose patients faster and earlier in their diseases without the need for a potentially risky procedure. We are currently working on creating an assay that can be tested clinically. We are also identifying markers that can diagnose acute kidney injury, predict whether patients with acute kidney injury will require dialysis and predict which diabetic patients are at greatest risk of developing kidney disease. Future studies will test these markers. Identification and testing of protein biomarkers can improve treatment and prolong and improve the lives of the millions of patients with kidney disease.
Varghese, S.A., T.B. Powell, M.N. Budisavljevic, J.C. Oates, J.R. Raymond, J.S. Almeida and J.M. Arthur. Urine biomarkers predict the cause of glomerular diseases. J. Am. Soc. Neph. 18:913-922, 2007.
Janech, M.G., Raymond, J.R., and J.M. Arthur. Proteomics in renal research. Am. J. Physiol. Renal Physiol. 292:F501-F512, 2007.
Arthur, J.M. and Powell T.B. Urinary Biomarkers in Diabetes and Other Glomerular Diseases. In: Clinical Proteomics: From Diagnosis to Therapy. Ed J. Van Eyk and M. Dunn, Wiley-VCH, In Press, 2007.
Arthur, J.M., M.N. Budisavljevic, S.A. Varghese and T.B. Powell. Proteomics and Acute Renal Failure. In: Critical Care Nephrology. Ed C. Ronco, R. Bellomo, and J. Kellum. In Press 2007.
Outcomes Following Correction of Anemia in Chronic Kidney Diseases (Dr. Sturdivant)
The Anemia Clinic opened in February 2003 in response to a need to better manage patients with anemia of Chronic Kidney Disease (CKD). The clinic is staffed by a clinical pharmacy specialist and a nephrology nurse practitioner who see patients under a protocol approved by a physician medical director. The focused clinic which utilizes an electronic medical record facilitates clinical research related to patients with anemia and CKD. Previous research efforts within the clinic have included a comparison of outcomes of anemia treatment between usual care with nephrologists and mid-level care providers in a dedicated setting. The clinic is also an ideal setting for industry sponsored pharmaceutical research related to anemia and has supported research related to intravenous iron compounds and erythropoietin stimulating agents. In addition, the clinic database and electronic medical record assist in identifying patients with CKD who may have other co-morbidites relevant to study.
Robey JT+, Gadegbeku CA, Uber L, Brooks DH, Sturdivant RL. Anemia Clinic: Improving Quality of Life by Improving Anemia Management associated with Chronic Kidney Disease. Abstract and poster presentation Nat Kid Fnd: Spring 2004.
Robey JT +, Sturdivant RL, Uber L, Brooks DH, Barnes PharmD. Improving Anemia Management for Chronic Kidney Disease Patients
Immediately Prior to the Initiation of Renal Replacement Therapy." Abstracts of the Am Soc Nephrol: November 2004.
Collaborative Focal Segmental Glomerular Sclerosis Trial (Dr. Budisavljevic):
In cooperation with the University of North Carolina, Chapel Hill, Dr. Milos Budisavljevic is the lead investigator involved in the MUSC Component of an NIH sponsored study entitled “Focal glomerulosclerosis clinic trial”. The objective of this randomized trial is to compare the effectiveness of cyclosporine to MMF combined with pulse corticosteroids in the treatment of corticosteroid resistant focal segmental glomerulosclerosis. The primary objective is to compare the induction of remission of proteinuria after 52 weeks of treatment with the various protocols. The remission of proteinuria 26 weeks after withdrawn of therapy will also be compared. Additional objectives include differences between the two treatment groups in quality of life, number of adverse events and extrarenal complications as well as preservation of renal function.
AASK Multicenter Clincal Trial & AASK Cohort Multicenter Clincal Trial:
The AASK Study randomized 1176 African-American subjects between 18-70 years of age, with hypertension and impaired renal function defined by glomerular filtration rates between 20 and 65ml/min. Those subjects who qualified were randomized to one of three drug treatment regimens and to one of two goal blood pressure0 levels, normal and low. The goal of therapy was to maintain blood pressure within the participant's randomized BP range. Glomerular filtration rates were measured semiannually during the 4 year follow-up period. MUSC AASK Study recruited 65 patients, one of the highest recruitment rates of all centers. Results from the trial found that angiotensin-converting enzyme inhibitors appear to be more effective than beta blockers or dihydropyridine calcium channel blockers in slowing the rate so GFR decline. No additional benefit of slowing hypertensive nephrosclerosis disease was found with the lower blood pressure goal. (JAMA, 11/20/02, vol 288, no 19, 2002, Results from the AASK trial - JAMA Article).
The AASK Cohort Multicenter Clincal Trial is the ongoing observational study for the longer term follow-up of the AASK population. MUSC is participating in the AASK Cohort Study: D. Cheek, MD, P.I. AASK particpants who had not reached end stage disease are being followed for blood pressure, progression of renal dysfunction and monitoring of cardiovascular events including LVH, MI and CVA. MUSC enrolled 47 participants in the Cohort.
- The Division of Nephrology is involved in several Phase 3 and phase 4 clinical trials sponsored by pharmaceutical/device companies at any given time. Presently several such trials are ongoing (Drs. Gupta, Ulozas, Arthur, Ploth).