It is well known that acute kidney injury (AKI) has a marked impact on clinical outcomes, including short-term mortality. Futhermore, the incidence of AKI has increased over the past several years. At the same time, the prevalence of chronic kidney disease is high and results in a major burden for patients and for the health care system in the United States. It is unclear if AKI is a completely reversible disease, or whether it leads to permanent kidney damage and thus CKD and death. This proposal will utilize a prospective cohort design that will add a long-term follow-up component to an ongoing multi-center 5-day study of urinary biomarkers for the detection of AKI after cardiac surgery. We will longitudinally study the patients with AKI as defined by at least a 25% increase in peri-operative serum creatinine and an equal number of patients without AKI that survive cardiac surgery at three academic centers. We will determine if AKI results in an increase in the decline in glomerular filtration rate and in increase in the protein excretion rate over time. We will compare the incidence of doubling of serum creatinine, dialysis or death in patients with and without AKI. In addition, we will examine if newly discovered biomarkers of acute kidney injury (urinary IL-18 and NGAL) are associated with CKD and death. As troponin has shown tremendous value in the setting of myocardial infarction, our hope is that these urinary biomarkers will possess long-term prognostic value for patients with AKI. Currently, AKI is viewed by most physicians as a reversible phenomenon that has little consequence after the acute phase. If, however, AKI is truly associated with long-term morbidity and mortality, then post-AKI care of these patients should involve closer vigilance and more aggressive treatments in order to improve long-term outcomes. My hope is to obtain R01 grants in the future with the goal of improving risk- stratification of AKI and I also hope to participate in multi-center trials of therapies for AKI and its associated complications.

Public Health Relevance

The relationship between acute kidney injury and long-term outcomes remains unclear. These studies will attempt to determine the association between both traditional kidney exposure variables (e.g., acute change in serum creatinine) and novel kidney exposure variables (e.g., urinary biomarkers) and long-term kidney and mortality outcomes in a cohort of cardiac surgery 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 #
5K23DK080132-04
Application #
8119718
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2008-08-01
Project End
2013-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
4
Fiscal Year
2011
Total Cost
$195,286
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G et al. (2017) Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery. J Am Soc Nephrol 28:3699-3707
Park, Meyeon; Shlipak, Michael G; Thiessen-Philbrook, Heather et al. (2016) Association of Peak Changes in Plasma Cystatin C and Creatinine With Death After Cardiac Operations. Ann Thorac Surg 101:1395-401
Coca, Steven G; Nadkarni, Girish N; Garg, Amit X et al. (2016) First Post-Operative Urinary Kidney Injury Biomarkers and Association with the Duration of AKI in the TRIBE-AKI Cohort. PLoS One 11:e0161098
Coca, Steven G; Zabetian, Azadeh; Ferket, Bart S et al. (2016) Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials. J Am Soc Nephrol 27:2529-42
Belley-Côté, Emilie P; Parikh, Chirag R; Shortt, Colleen R et al. (2016) Association of cardiac biomarkers with acute kidney injury after cardiac surgery: A multicenter cohort study. J Thorac Cardiovasc Surg 152:245-251.e4
Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather et al. (2016) Methodological issues in current practice may lead to bias in the development of biomarker combinations for predicting acute kidney injury. Kidney Int 89:429-38
Zhang, William R; Garg, Amit X; Coca, Steven G et al. (2015) Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery. J Am Soc Nephrol 26:3123-32
Koyner, Jay L; Coca, Steven G; Thiessen-Philbrook, Heather et al. (2015) Urine Biomarkers and Perioperative Acute Kidney Injury: The Impact of Preoperative Estimated GFR. Am J Kidney Dis 66:1006-14
Moledina, Dennis G; Parikh, Chirag R; Garg, Amit X et al. (2015) Association of Perioperative Plasma Neutrophil Gelatinase-Associated Lipocalin Levels with 3-Year Mortality after Cardiac Surgery: A Prospective Observational Cohort Study. PLoS One 10:e0129619
Zappitelli, Michael; Greenberg, Jason H; Coca, Steven G et al. (2015) Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery. JAMA Pediatr 169:583-91

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