Over a 100,000 persons in the US started dialysis and more than 350,000 people were on maintenance dialysis in 2006;a number expected to grow to over half a million by the year 2020. The high first-year mortality for incident dialysis patients has not decreased in the last 11 years and 60% of the dialysis patients die within five years of starting dialysis. Therapies to improve dialysis care are sorely needed but most recent clinical trials to reduce dialysis mortality have been negative. Kidney function after starting dialysis, referred to as residual kidney function (RKF), is a strong predictor of survival in dialysis patients. RKF, even at the low levels present in dialysis patients is important for clearing uremic toxins and preventing volume overload and its sequelae such as hypertension and heart failure. Preserving RKF, as an integral part of an overall dialysis care plan, offers the hope of improving dialysis care and improving the dismal dialysis survival. RKF, however, is difficult to assess. There are no methods for assessing RKF similar to the estimation of GFR by serum creatinine in non-dialysis patients. Timed urine collection, performed over 24-48 hours is the only method available at this time to assess RKF in dialysis patients. The overall goals of this proposal are: (1) to develop simple methods for direct measurement of GFR in dialysis patients using a very small dose of iohexol, a radiologic contrast agent referred to as the new standard for measuring GFR, (2) test if two endogenous low molecular weight proteins (beta-trace protein [BTP] and cystatin C), that are excellent serum markers of GFR but not removed by dialysis, can be used to estimate GFR in dialysis patients similar to the estimation of GFR from serum creatinine in non-dialysis patients, (3) determine the risk of mortality and morbidity associated with low RKF, and (4) design and conduct a pilot randomized clinical trial to determine if RKF can be preserved by treatment with angiotensin converting enzyme inhibitors. The candidate for this mentored Career Development Award is an Instructor of Medicine in the Division of Nephrology at Johns Hopkins University and his career goal is to become an independent clinician-investigator in the area of end-stage renal disease (ESRD). This award will allow him to undergo a rigorous program of didactic education in epidemiology and biostatistics complemented with a practical experience in conducting clinical research. These structured career development activities, occurring under the close guidance and supervision of leaders in the field of kidney disease epidemiology, the supportive environment of Johns Hopkins University as well as the Welch Center for Prevention, Epidemiology, and Clinical Research will allow him to answer important scientific questions and develop into an independent clinical investigator.

Public Health Relevance

Survival on dialysis is poor with only 4 out of 10 people surviving beyond 5 years. Kidney function, even after start of dialysis, plays an important role in clearing kidney failure toxins and improves survival. This research project will develop methods for measuring kidney function in dialysis patients and test if treatment with angiotensin converting enzyme inhibitors can preserve kidney function in dialysis patients. Survival on dialysis is poor with only 4 out of 10 people surviving beyond 5 years. Kidney function, even after start of dialysis, plays an important role in clearing kidney failure toxins and improves survival. This research project will develop methods for measuring kidney function in dialysis patients and test if treatment with angiotensin converting enzyme inhibitors can preserve kidney function in dialysis patients.

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 #
5K23DK083514-05
Application #
8705499
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2010-08-09
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$182,125
Indirect Cost
$13,491
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Shafi, Tariq; Zager, Philip G; Sozio, Stephen M et al. (2014) Troponin I and NT-proBNP and the association of systolic blood pressure with outcomes in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. Am J Kidney Dis 64:443-51
Scialla, Julia J; Liu, Jiannong; Crews, Deidra C et al. (2014) An instrumental variable approach finds no associated harm or benefit with early dialysis initiation in the United States. Kidney Int 86:798-809
Crews, Deidra C; Scialla, Julia J; Boulware, L Ebony et al. (2014) Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD. Am J Kidney Dis 63:806-15
Jaar, Bernard G; Zhang, Lili; Chembrovich, Svetlana V et al. (2014) Incidental findings on cardiac computed tomography in incident hemodialysis patients: the predictors of arrhythmic and cardiovascular events in end-stage renal disease (PACE) study. BMC Nephrol 15:68
Crews, Deidra C; Scialla, Julia J; Liu, Jiannong et al. (2014) Predialysis health, dialysis timing, and outcomes among older United States adults. J Am Soc Nephrol 25:370-9
Scialla, Julia J; Kao, W H Linda; Crainiceanu, Ciprian et al. (2014) Biomarkers of vascular calcification and mortality in patients with ESRD. Clin J Am Soc Nephrol 9:745-55
Miskulin, Dana C; Tangri, Navdeep; Bandeen-Roche, Karen et al. (2014) Intravenous iron exposure and mortality in patients on hemodialysis. Clin J Am Soc Nephrol 9:1930-9
Shafi, Tariq; Waheed, Sana; Zager, Philip G (2014) Hypertension in hemodialysis patients: an opinion-based update. Semin Dial 27:146-53
Shafi, Tariq; Sozio, Stephen M; Bandeen-Roche, Karen J et al. (2014) Predialysis systolic BP variability and outcomes in hemodialysis patients. J Am Soc Nephrol 25:799-809
Shafi, Tariq; Sozio, Stephen M; Plantinga, Laura C et al. (2013) Serum fructosamine and glycated albumin and risk of mortality and clinical outcomes in hemodialysis patients. Diabetes Care 36:1522-33

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