Untitled Document

Research

Lisa Nanovic

D.O., Chicago College of Osteopathic Medicine
Assistant Professor, Department of Medicine, Nephrology
ln3@medicine.wisc.edu
http://www2.medicine.wisc.edu/home/people-search/people/staff/3054/NANOVIC_LISA_M/

Effect of ACE-inhibitors on Aortic Stiffness in Elderly Patients with Chronic Kidney Disease

Individuals with Chronic Kidney Disease (CKD) can manifest a 10 to100-fold increase in cardiovascular (CV) morbidity and mortality, depending on their age and gender. In a sample of patients over 65 years of age without previous CV complications it was demonstrated that increased arterial stiffening significantly predicts future CV complications. Worsening CKD (stages 3 to 5) is associated with increased aortic stiffness.

The prevalence of CKD is higher among the elderly. Although more than 7 million people have moderate CKD (stage 3) in the US, only 500,000 survive to the dialysis stage (stage 5), as the majority die of CV complications. Early markers of CVD would enable clinicians to intervene earlier to prevent and treat risk factors for CV disease in patients with CKD.

Not only do the elderly have increased cardiovascular risk due to effects on the intimal portion of the vasculature during the normal process of aging, but those having CKD have additional vascular pathology with increased collagen deposition and subsequent decreased elasticity of the medial aspect of their vasculature. This possible additive effect on the vasculature could potentially cause a significant increase in the CV morbidity and mortality in persons over age 65.

Histological findings associated with aortic stiffening are a result of increased collagen deposition. Angiotensin II is involved in increased collagen deposition and release of growth factors in the vascular wall. Inhibitors of angiotensin II, including angiotensin converting enzyme inhibitors (ACE-I), are currently used to control hypertension and delay disease progression in CKD. These well characterized inhibitors present an opportunity to target arterial stiffness.

The goal of this proposal is to investigate the potential for ACE-I to prevent or delay CV disease in older adults with CKD by examining their impact on aortic stiffness in people with stage 3 CKD in a randomized, controlled study. The specific aims of this research project are to:

1. Compare vascular stiffening in patients over age 65 with stage 3 CKD to age matched controls.
2. Evaluate the effect of ACE-inhibitors on aortic stiffness as measured by pulse wave velocity (PWV) at baseline and 12 months in patients > 65 years of age with stage 3 CKD.
3. Evaluate the effects of ACE-inhibitors on clinical and subclinical markers of CV disease in stage 3 CKD.

My long term career goal is to become an academic nephrologist leading a clinical research program investigating vascular stiffness in patients with CKD. Aortic stiffness in the geriatric population is the first step for further evaluation of the cardiovascular abnormalities unique to this population of CKD patients. Not only can this concept be expanded into a larger clinical trial, but it can also evolve into translational research with investigation into the pathophysiology of uremic changes in the vasculature at a cellular and molecular level. Reaching these long-term career goals are attainable through the American Society of Nephrology-ASP Junior Career Development Award in Geriatric Medicine, and the continued support of my expert mentoring team: Molly Carnes, MD, Nancy Sweitzer, MD, PhD, and Bryan Becker, MD.

Representative Publications
Nanovic, L., & Kaplan, B. (2009). The advantage of live-donor kidney transplantation in older recipients. Nat. Clin. Pract. Nephrol., 5(1), 18-9.

Kukla, A., Adulla, M., Pascual, J., Samaniego, M., Nanovic, L., Becker, B.N., & Djamali, A. (2008). CKD stage-to-stage progression in native and transplant kidney disease. Nephrol. Dial. Transplant, 23(2), 693-700.

Nanovic, L.M., Djamali, A. (2008). Definition and prevalence of anemia in renal transplant recipients. In J.M. Grinyo (Ed.), Anemia in transplantation, international transplantation updates. Barcelona, Spain: Permanyer Publications.

Sanghvi, S.R., Kellerman, P.S., & Nanovic, L. (2007). Beer potomania: an unusual cause of hyponatremia at high risk of complications from rapid correction. Am. J. Kidney Dis., 50(4), 673-80.

Baba, F., Nanovic, L., Jaffery, J.B., & Friedl, A. (2006). Karyomegalic tubulointerstitial nephritis--a case report. Pathol. Res. Pract., 202(7), 555-9.

Nanovic, L., Becker, Y.T., Hedican, S., & Hofmann, R.M. (2005). Sudden late onset of gross hematuria in a previous renal transplant recipient 3 months after transplant nephrectomy. Am. J. Kidney Dis., 46(5), e91-4.

Nanovic, L. (2005). Electrolytes and fluid management in hemodialysis and peritoneal dialysis. Nutr. Clin. Pract., 20(2), 192-201.

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