Patients with chronic kidney disease (CKD) are at increased risk for various adverse health outcomes including cardiovascular disease. However, the rate of progression of CKD varies widely among patients, even when corrected for the etiology of renal disease and co-morbid conditions. Because high levels of circulating cytokines are observed in renal disease, it is plausible that cytokines, though naturally occurring sequence variation (polymorphisms) in their genes, modulate the rate of progression of CKD and the susceptibility to CVD outcomes. The central hypothesis of this application is that cytokine gene polymorphisms, through altered expression of pro- fibrotic and inflammatory cytokines, will modulate the rates of progression of renal disease and incidence of CVD among CKD patients. The principal aims of this proposal are: (1) Determine the prevalence of cytokine gene polymorphisms and haplotypes of interleukin-1 (IL-1), IL-1 receptor antagonist, IL-6, IL-10, tumor necrosis factor-a, and transforming growth factor-p among chronic renal insufficiency cohort (CRIC) participants; and (2) Evaluate the association between specific gene polymorphisms/haplotypes and (a) plasma cytokines, (b) the rate of decline of renal function, and (c) incidence of, severity of and mortality from CVD in the CRIC cohort. Methods: The CRIC study is examining the progression of renal and CV diseases, and health outcome variables in a large cohort of patients with CKD. In order to achieve this aim, a cohort of 3,000 patients with varying level of renal function will be followed for approximately 5 years. CRIC consortium promotes and participates in ancillary studies that complement the principal aims of the parent CRIC study. The CRIC steering committee has critically evaluated and approved this ancillary proposal. We will use the biological samples and clinical data compiled by the parent CRIC study. For genotyping cytokine genes of interest, we will combine a candidate single nucleotide polymorphism (SNP) and tag-SNP approach, for which race-specific panels of tag-SNPs will be chosen. Haplotypes for each gene will be inferred from all genotyped tag-SNPs and selected functional SNPs. Plasma cytokine levels will be measured at baseline and at the 4th year of follow-up. The association of cytokine alleles and haplotypes with plasma cytokine levels and clinical outcome measures will be determined by appropriate statistical modeling. Significance: Identification of the high risk genotypes can lead to early and aggressive interventions aimed at the target population. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK073665-03
Application #
7460917
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M5))
Program Officer
Rasooly, Rebekah S
Project Start
2006-09-01
Project End
2009-06-01
Budget Start
2008-07-01
Budget End
2009-06-01
Support Year
3
Fiscal Year
2008
Total Cost
$407,244
Indirect Cost
Name
University of New Mexico
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Roumelioti, Maria-Eleni; Glew, Robert H; Khitan, Zeid J et al. (2018) Fluid balance concepts in medicine: Principles and practice. World J Nephrol 7:1-28
Munoz Mendoza, Jair; Isakova, Tamara; Cai, Xuan et al. (2017) Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease. Kidney Int 91:711-719
Muralidharan, Jagdeesan; Ramezani, Ali; Hubal, Monica et al. (2017) Extracellular microRNA signature in chronic kidney disease. Am J Physiol Renal Physiol 312:F982-F991
Alaini, Ahmed; Malhotra, Deepak; Rondon-Berrios, Helbert et al. (2017) Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate. World J Methodol 7:73-92
Nallu, Anitha; Sharma, Shailendra; Ramezani, Ali et al. (2017) Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res 179:24-37
Velasquez, Manuel T; Beddhu, Srinivasan; Nobakht, Ehsan et al. (2016) Ambulatory Blood Pressure in Chronic Kidney Disease: Ready for Prime Time? Kidney Int Rep 1:94-104
Amdur, Richard L; Feldman, Harold I; Gupta, Jayanta et al. (2016) Inflammation and Progression of CKD: The CRIC Study. Clin J Am Soc Nephrol 11:1546-56
Ramezani, Ali; Massy, Ziad A; Meijers, Björn et al. (2016) Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. Am J Kidney Dis 67:483-98
Ramezani, Ali; Barrows, Ian R; Raj, Dominic S (2015) Electroacupuncture therapy for muscle atrophy in CKD: is there a needle in the haystack? J Am Soc Nephrol 26:510-2
Kelly, Tanika N; Raj, Dominic; Rahman, Mahboob et al. (2015) The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Nephrol Dial Transplant 30:1711-8

Showing the most recent 10 out of 33 publications