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Racial Differences In Phosphorus Metabolism In Health And In Kidney Disease

Orlando M Gutierrez
Medicineuniversity Of Miami School Of Medicine
1507 Levante Avenue
coral Gables, Fl 33124

Grant 1K23DK081673-01 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: DDK

Abstract: 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. 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

Project start date: 2008-08-01

Project end date: 2013-06-30

1K23DK081673-01 (2008): $136350


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Grants awarded to Orlando M Gutierrez

RACIAL DIFFERENCES IN PHOSPHORUS METABOLISM IN HEALTH AND IN KIDNEY DISEASE

Orlando M Gutierrez
University Of Miami School Of Medicine, Po Box 016960 (r-64), Miami, Fl 33101

Grant 5K23DK081673-03 from National Institute Of Diabetes And Digestive And Kidney Diseases

Abstract: 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. 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

Keywords: 3`5`-cyclic ester of AMP; Absorption; Accounting; Adenosine Cyclic 3`, 5`-Monophosphate; Adenosine Cyclic Monophosphate; Adenosine, cyclic 3`, 5`-(hydrogen phosphate); Blood Coagulation Factor IV; Blood Pressure, High; Blood Serum; Ca++ element; Calcium; Cardiovascular; Cardiovascular Body System; Cardiovascular Diseases; Cardiovascular system; Cardiovascular system (all sites); Care, Health; Chemotherapy-Hormones/Steroids; Chronic Kidney Failure; Chronic Renal Disease; Clinical Investigator; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Coagulation Factor IV; Cyclic AMP; Data; Diabetes Mellitus; Dialysis; Dialysis procedure; Diet; Dietary intake; Disease Outcome; Disease Progression; ESRD; End stage renal failure; End-Stage Kidney Disease; Endocrine Gland Secretion; Ensure; Epidemic; Excretory function; FGF23 gene product; Factor IV; General Hospitals; Glomerular Filtration Rate; Goals; Health; Healthcare; High Prevalence; Hormonal; Hormones; Human; Human, General; Hypertension; Individual; Infusion; Infusion procedures; Intake; Intermediary Metabolism; Internal Medicine; Investigation; Investigators; K23 Award; K23 Mechanism; K23 Program; Kidney; Kidney Diseases; Kidney Failure; Kidney Failure, Chronic; Kidney Insufficiency; Link; METBL; Man (Taxonomy); Man, Modern; Massachusetts; Master`s Degree; Measures; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Mentored Patient-Oriented Research Career Development Award (K23); Mentors; Metabolic Processes; Metabolism; Mortality; Mortality Vital Statistics; Nephrology; Nephrons; Nephropathy; Oral; Organ System, Cardiovascular; PTH (1-84); PTH protein, human; Parathyroid Hormone; Parathyroid Hormone (1-84); Parathyroid Hormones; Phosphates; Physiologic; Physiological; Poverty; Prevalence; Process of absorption; Programs (PT); Programs [Publication Type]; Public Health; Race; Racial Group; Relative; Relative (related person); Renal Disease; Renal Disease, End-Stage; Renal Failure; Renal Failure, Chronic; Renal Insufficiency; Research; Research Personnel; Research Training; Researchers; Residencies; Resistance; Risk Factors; Serum; Staging; Stimulus; Stocks, Racial; Testing; Therapeutic Hormone; Time; Training; Universities; Urinary System, Kidney; Uriniferous Tube; VIT D; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Vascular, Heart; Vitamin D; absorption; adenosine 3`5` monophosphate; base; cAMP; cardiovascular disorder; career development; chronic kidney disease; circulatory system; clinical investigation; diabetes; dialysis therapy; excretion; feeding; fibroblast growth factor 23; hPTH(1-84); hormonal regulation; hormone regulation; human PTH protein; hyperpiesia; hyperpiesis; hypertensive disease; improved; inorganic phosphate; insight; kidney disorder; medical schools; new therapeutic target; novel; parathormone; parathyroid hormone, human; patient centered; patient oriented; phosphorus metabolism; programs; public health medicine (field); public health relevance; race differences; racial difference; renal; renal disorder; resistant; response; skills; success; training project; urinary

Project start date: 2008-08-01

Project end date: 2013-06-30

Budget start date: 1-JUL-2010

Budget end date: 30-JUN-2011

PFA/PA: PA-05-143

5K23DK081673-03 (2010): $137730


5K23DK081673-02 (2009): $137160