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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Rankin, Tracy L
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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Shafi, Tariq; Sirich, Tammy L; Meyer, Timothy W et al. (2017) Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes. Kidney Int 92:1484-1492
Banerjee, Tanushree; Meyer, Timothy W; Shafi, Tariq et al. (2017) Free and total p-cresol sulfate levels and infectious hospitalizations in hemodialysis patients in CHOICE and HEMO. Medicine (Baltimore) 96:e5799
Michels, Wieneke M; Jaar, Bernard G; Ephraim, Patti L et al. (2017) Intravenous iron administration strategies and anemia management in hemodialysis patients. Nephrol Dial Transplant 32:173-181
Shafi, Tariq; Powe, Neil R; Meyer, Timothy W et al. (2017) Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients. J Am Soc Nephrol 28:321-331
Shafi, Tariq; Hostetter, Thomas H; Meyer, Timothy W et al. (2017) Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients. Am J Kidney Dis 70:48-58
Inker, Lesley A; Tighiouart, Hocine; Coresh, Josef et al. (2016) GFR Estimation Using ?-Trace Protein and ?2-Microglobulin in CKD. Am J Kidney Dis 67:40-8
Kruzan, Rachel M; Herzog, Charles A; Wu, Aozhou et al. (2016) Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study. BMC Nephrol 17:18
Shafi, Tariq; Michels, Wieneke M; Levey, Andrew S et al. (2016) Estimating residual kidney function in dialysis patients without urine collection. Kidney Int 89:1099-1110
Meyer, Timothy W; Sirich, Tammy L; Fong, Kara D et al. (2016) Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study. J Am Soc Nephrol 27:3469-3478
Shafi, Tariq; Levey, Andrew S; Inker, Lesley A et al. (2015) Plasma Iohexol Clearance for Assessing Residual Kidney Function in Dialysis Patients. Am J Kidney Dis 66:728-30

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