The primary objective of this research proposal, entitled """"""""Urinary biomarkers for recovery after acute kidney injury and prognosis in hospitalized patients,"""""""" is to evaluate the relationship between early urinary biomarker levels and subsequent recovery patterns as well as other patient outcomes (e.g. length of stay and in-hospital mortality) in a prospective cohort of 200 general hospitalized patients with acute kidney injury (AKI). AKI in the hospital is frequently unpredictable and most often diagnosed by an increase in serum creatinine (Scr) concentrations on routine daily blood draws. Scoring systems to predict patient outcomes based on demographic and other clinical information have been proposed, but are rarely used by clinicians in everyday practice. Several novel biomarkers of kidney tissue damage have been validated in humans and have the potential, at the earliest sign of injury, to differentiate between patients who will recover kidney function quickly with little to no lasting effects and those who will not. The methods of the proposed study are as follows. Two urine samples will be collected from patients 18 years of age or older admitted to Yale-New Haven Hospital, one on the same morning that a rise in Scr of at least 0.3 mg/dL is noted by routine labs and another on the following morning. Relevant clinical data will be collected prospectively. Urines samples will be processed and frozen for later blinded, batched measurement of biomarkers such as interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C. The cohort will be grouped by levels of urinary biomarkers to compare rates of subsequent dialysis, time to return to baseline kidney function, and in-hospital mortality. Mann-Whitney U tests, receiver-operating characteristic curve analysis, logistic regression, and tests for the net reclassification index will be used to assess the prognostic utility of the biomarkers in this cohort of general hospitalized patients. There is a known association between the development of AKI and mortality, and data suggest an association between AKI and subsequent chronic kidney disease. The burdens of this illness are substantial and worthy of continued research. The prognostic value that accurate and early biomarkers could have with regard to hospital resource allocation, patient follow-up, chronic kidney disease surveillance, and decisions about continued use of nephrotoxic medications would be of profound importance in hospitalized patients. This proposal is directly in line with the mission of the NIH to improve understanding of living systems and apply that knowledge to reduce the burdens of illness and disability.

Public Health Relevance

Approximately five percent of all patients and two-thirds of those in intensive care units develop kidney injury at some point during their hospitalization. While the majority of patients improve with no apparent short-term consequences, a certain proportion progress to overt kidney failure, which leads to multiple complications and requires dialysis for life support. This study aims to identify, at the earliest possible time point, which patients are most likely to have complications related to kidney injury in order to provide safer care and reduce the potential for greater injury in the hospital.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-G (J1))
Program Officer
Rankin, Tracy L
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Hall, Isaac E; Stern, Edward P; Cantley, Lloyd G et al. (2014) Urine YKL-40 is associated with progressive acute kidney injury or death in hospitalized patients. BMC Nephrol 15:133
Hall, Isaac E; Doshi, Mona D; Reese, Peter P et al. (2012) Association between peritransplant kidney injury biomarkers and 1-year allograft outcomes. Clin J Am Soc Nephrol 7:1224-33
Hall, Isaac E; Koyner, Jay L; Doshi, Mona D et al. (2011) Urine cystatin C as a biomarker of proximal tubular function immediately after kidney transplantation. Am J Nephrol 33:407-13
Hall, Isaac E; Coca, Steven G; Perazella, Mark A et al. (2011) Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis. Clin J Am Soc Nephrol 6:2740-9
Hall, Isaac E; Doshi, Mona D; Poggio, Emilio D et al. (2011) A comparison of alternative serum biomarkers with creatinine for predicting allograft function after kidney transplantation. Transplantation 91:48-56
Perazella, Mark A; Coca, Steven G; Hall, Isaac E et al. (2010) Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 5:402-8