Candidate: Orlando Gutierrez received his MD from the University of Toledo, and completed his Internal Medicine Residency at the Massachusetts General Hospital. He is currently a clinical and research fellow in nephrology at MGH, and a candidate for a Master's degree in human physiological investigation from Harvard Medical School. Mentor: Dr. David Nathan is a renowned clinical investigator who has trained numerous investigators in patient-oriented clinical research. Dr. Nathan will ensure the success of Dr. Gutierrez's research training, project, and overall career development. Research: Blacks with chronic kidney disease (CKD) progress to end stage renal disease and develop cardiovascular disease (CVD) more rapidly than Whites. The mechanisms that underlie these disparities remain elusive. Hyperphosphatemia is linked with both accelerated kidney and CVD progression. Parathyroid hormone (PTH) and Fibroblast Growth Factor 23 (FGF-23) are the primary hormones that regulate serum phosphate (Pi) levels. Preliminary data from our group indicate that Blacks with CKD have a higher prevalence of hyperphosphatemia than Whites at all levels of glomerular filtration rate despite higher PTH levels, suggesting that Blacks have impaired Pi excreting capacity. Impaired Pi excretion may represent a novel risk factor for faster kidney and CV disease progression in Blacks. However, no studies have examined differences in Pi handling by race.
For Aim 1, we will examine racial differences in gut and renal Pi handling by measuring (1) gut Pi absorption after a fixed Pi meal and (2) dynamic changes in urinary Pi excretion in response to oral Pi loading in healthy Blacks vs. Whites.
For Aim 2, we will examine racial differences in hormonal reguation of Pi metabolism by comparing (1) the phosphaturic effect of synthetic PTH infusion and (2) dynamic changes in FGF-23 levels after oral Pi loading in healthy Blacks vs. Whites.
For Aim 3, we will examine racial differences in Pi handling in CKD by measuring urinary Pi excretion in response to dietary Pi loading in Blacks vs. Whites with CKD. We will then compare any differences in CKD to those seen in healthy individuals. We believe the results of these studies will provide critical new insights into racial differences in Pi metabolism that may help elucidate racial disparities in CKD outcomes with important public health implications. A K23 award will allow Dr. Gutierrez to attain new skills in clinical investigation and develop into an independent clinical investigator.

Public Health Relevance

We believe the results of these studies will provide critical new insights into racial differences in serum phosphate metabolism that may help elucidate racial disparities in chronic kidney disease outcomes with important public health implications.

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 #
5K23DK081673-06
Application #
8296704
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2008-08-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
6
Fiscal Year
2012
Total Cost
$137,970
Indirect Cost
$10,220
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
Hanks, Lynae J; Casazza, Krista; Ashraf, Ambika P et al. (2015) Fibroblast growth factor-21, body composition, and insulin resistance in pre-pubertal and early pubertal males and females. Clin Endocrinol (Oxf) 82:550-6
GutiƩrrez, Orlando M; Muntner, Paul; Rizk, Dana V et al. (2014) Dietary patterns and risk of death and progression to ESRD in individuals with CKD: a cohort study. Am J Kidney Dis 64:204-13
Carrigan, Anna; Klinger, Andrew; Choquette, Suzanne S et al. (2014) Contribution of food additives to sodium and phosphorus content of diets rich in processed foods. J Ren Nutr 24:13-9, 19e1
Gutierrez, Orlando M (2013) Sodium- and phosphorus-based food additives: persistent but surmountable hurdles in the management of nutrition in chronic kidney disease. Adv Chronic Kidney Dis 20:150-6
Gutierrez, Orlando M (2013) The connection between dietary phosphorus, cardiovascular disease, and mortality: where we stand and what we need to know. Adv Nutr 4:723-9
Saxena, Nakshatra; Gutierrez, Orlando M (2013) Fibroblast growth factor 23, vitamin D, and health disparities among African Americans with chronic kidney disease. Semin Nephrol 33:448-56
Gutierrez, Orlando M (2013) Fibroblast growth factor 23, Klotho, and disordered mineral metabolism in chronic kidney disease: unraveling the intricate tapestry of events and implications for therapy. J Ren Nutr 23:250-4
Gutierrez, Orlando M; Khodneva, Yulia A; Muntner, Paul et al. (2013) Association between urinary albumin excretion and coronary heart disease in black vs white adults. JAMA 310:706-14
Gutierrez, Orlando M; Smith, Kelsey T; Barchi-Chung, Allison et al. (2012) (1-34) Parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers. Clin J Am Soc Nephrol 7:139-45
Gutierrez, Orlando M (2011) Recent insights into racial differences in bone and mineral metabolism. Curr Opin Endocrinol Diabetes Obes 18:347-51

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