This proposal is the second revision of grant 1 K23 DK 064649-01. The reviewers' comments have been carefully reviewed and incorporated into this revision. Given the anticipated sharp increases in type 2 diabetic nephropathy in the US, and the resulting rise in end stage renal disease, diabetic nephropathy represents an urgent area of interest, as acknowledged in the Healthy People 2000 report. During the proposed grant period, Dr. Ruth C. Campbell will work to become an independent investigator in the field of progression of chronic kidney disease with an emphasis on diabetic nephropathy. She will accomplish these goals under the combined guidance of her mentors, Drs. Stephen Rostand and Paul Sanders. She will complete a Master's Degree of Science Public Health in Clinical Studies, a post doctoral program aimed to assist clinicians gain skills in epidemiology, statistics and public health issues. This will give her the necessary skills in clinical study design and statistical analysis needed to become an independent investigator. She will also complete the project """"""""Effect of pioglitazone on proteinuria in type 2 diabetes."""""""" Pioglitazone is a member of the insulin sensitizing thiazolidinedione (TZD) class and has been approved for the treatment of type 2 diabetes. TZD agents affect the PPAR-gamma receptor and have other effects besides increasing insulin sensitivity. PPAR-gamma receptors have been found in the kidney and smooth muscle cells, suggesting other areas of possible activity. They have been found to lower blood pressure in animals and humans, and to reduce proteinuria in some animal models of both diabetic and non-diabetic nephropathy. They have also been shown to reduce TGF-beta levels in animal models of renal insufficiency. TZD compounds were found to reduce microalbuminuria in a small study of type 2 diabetic patients. It is unknown if they would have a similar effect in overt diabetic nephropathy. The proposed study would be an open-label, randomized, parallel arm trial comparing the effect of 24 weeks of pioglitazone therapy vs. non-TZD based diabetic therapy on 24-hour protein excretion in type 2 diabetic nephropathy in patients with persistent proteinuria despite treatment with an angiotensin 2-receptor antagonist. Secondary endpoints will be the effect of pioglitazone on urinary TGF-beta levels, urinary podocyte number, blood pressure, insulin resistance, glycemic control and renal hemodynamics

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK064649-04
Application #
7459924
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
4
Fiscal Year
2008
Total Cost
$111,633
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Aaron, Kristal J; Campbell, Ruth C; Judd, Suzanne E et al. (2011) Association of dietary sodium and potassium intakes with albuminuria in normal-weight, overweight, and obese participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Am J Clin Nutr 94:1071-8
Ahmed, Mustafa I; Ekundayo, O James; Mujib, Marjan et al. (2010) Mild hyperkalemia and outcomes in chronic heart failure: a propensity matched study. Int J Cardiol 144:383-8
Bowling, C Barrett; Pitt, Bertram; Ahmed, Mustafa I et al. (2010) Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies. Circ Heart Fail 3:253-60
Campbell, Ruth C; Sui, Xuemei; Filippatos, Gerasimos et al. (2009) Association of chronic kidney disease with outcomes in chronic heart failure: a propensity-matched study. Nephrol Dial Transplant 24:186-93
Alper, A Brent; Campbell, Ruth C; Anker, Stefan D et al. (2009) A propensity-matched study of low serum potassium and mortality in older adults with chronic heart failure. Int J Cardiol 137:1-8
Ritchie, Christine; Ekundayo, O James; Muchimba, Maureen et al. (2009) Effects of diabetes mellitus in patients with heart failure and chronic kidney disease: a propensity-matched study of multimorbidity in chronic heart failure. Int J Cardiol 134:330-5
Ekundayo, O James; Muchimba, Maureen; Aban, Inmaculada B et al. (2009) Multimorbidity due to diabetes mellitus and chronic kidney disease and outcomes in chronic heart failure. Am J Cardiol 103:88-92
Jain, Gaurav; Campbell, Ruth C; Warnock, David G (2009) Mineralocorticoid receptor blockers and chronic kidney disease. Clin J Am Soc Nephrol 4:1685-91
Ahmed, Ali; Campbell, Ruth C (2008) Epidemiology of chronic kidney disease in heart failure. Heart Fail Clin 4:387-99