RACE/ETHNIC MINORITY POPULATION
Effects of Age and Race on GFR Estimation in a Population-based Cohort
Principal Investigator: Michael G. Shlipak and Andrew Levey
Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK087961)
Project Summary: Chronic kidney disease is a public health problem that disproportionately affects racial and ethnic minorities in the US. The normal levels of kidney function and the accuracy of equations to estimate kidney function are not known in racial and ethnic minorities, which represent barriers to effective clinical practice, research and public health efforts for CKD in these groups. The goals of the proposed project are to characterize the usual levels of kidney function in racial and ethnic minorities; to develop more accurate ways to estimate kidney function in racial and ethnic groups.
HIV POPULATION
The Aging Kidney in HIV-Infection: biomarkers for early detection of injury
Principal Investigator: Michael G. Shlipak
Funding Source: National Institute of Aging (R01AG034853)
Project Summary: This grant adds novel biomarkers of injury to the microvasculature, tubules, and interstitium of the kidney and of bone mineral metabolism to the ongoing Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS). The objectives of this project include: to compare kidney injury markers among HIV-infected and uninfected participants cross-sectionally, and their association with age, tenofovir use, and GFR; to examine the link between HIV-infection, advancing age, declining GFR, and tenofovir use with the disorders of mineral metabolism and reduced bone mineral density; and to evaluate longitudinally whether baseline and follow-up markers of kidney injury are independently associated with accelerated declines in kidney function.
Kidney Health Biomarker Panels for Drug Toxcity and Prognosis in HIV-Infection
Principal Investigator: Michael Shlipak
Funding Source: National Institute of Aging (2R01AG034853-06A1)
Project Summary: We will evaluate 15 candidate urine biomarkers that quantify damage and dysfunction within distinct compartments of the kidney, and we will select the optimal combinations to maximize: 1) detection of kidney abnormalities at their earliest stages; 2) discernment of TDF specific damage; and 3) prognosis of kidney disease risk. To accomplish both development and validation stages for our biomarker combinations, we will conduct our research across five multi-center studies that have available biological specimens and that have welcomed our collaboration on this proposal: the Preexposure Prophylaxis Initiative trial (iPrEx), the Women's Interagency HIV Study (WIHS), the Multicenter AIDS Cohort Study (MACS), the Biopsy Examination of AIDS Nephropathy (BEANS), and the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN).
ELDERLY POPULATION
Impact of Exercise on Kidney Function and Injury among Elders in the LIFE Trial
Principal Investigator: Michael Shlipak and Steve Coca
Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases(1R01DK115562)
Project Summary: Chronic Kidney Disease (CKD) is increasingly recognized as a major comorbid condition in older adults. The burden of CKD is predominantly due to its adverse physiological effects that promote cardiovascular disease, heart failure, physical and cognitive functional declines, bone disease, and death. However, no large, randomized controlled trial (RCT) has ever been attempted with the objective of preventing or treating age-related kidney disease. The LIFE trial offers an ideal and efficient opportunity to test whether a physical activity intervention can improve kidney health in elders in an RCT setting. Our study proposes to transform LIFE into the first large trial among elders to evaluate the impact of exercise on kidney health. In summary, the LIFE study will allow determination of whether age-related kidney disease can be prevented in sedentary elders by a structured exercise intervention, and to evaluate the optimal exercise intensity and target population.
Role of Mitochondrial Health in Acute and Chronic Kidney Disease in Older Adults
Principal Investigator: Michael Shlipak
Funding Source: National Institute on Aging
Project Summary: Over the past decade of this award, we have made substantial progress toward understanding the adverse impact of chronic kidney disease (CKD) on the health of older adults. Kidney function declines steadily with age, even in the absence of any clinical risk factors, and reduced kidney function is strongly associated with myriad cardiovascular and non-cardiovascular morbidities. These results suggest that kidney tubular health is pivotal for understanding the development and progression of kidney disease. We will aim to evaluate whether mtDNA quantity and quality are associated with risk for acute kidney injury in persons undergoing cardiac surgery, evaluate associations of the same mtDNA measures with development of CKD and with progression to kidney failure, and utilize a suite of validated techniques to investigate mitochondrial health in situ using archived kidney tissue from older adults with and without kidney disease. We will compare measures of mitochondrial biogenesis, mitochondrial quantity, oxidative phosphorylation capacity, and ultrastructural appearance, and then evaluate their associations with histopathology and clinical status. These Aims will translate the emerging renal biology of mitochondria into human kidney disease in older adults.
The Aging Kidney: Chronic Injury, Impaired Functions and Clinical Outcomes
Principal Investigator: Michael G. Shlipak and Mark J. Sarnak
Funding Source: National Institute of Aging (5R01AG027002)
Project Summary: Chronic kidney disease, particularly prevalent in the elderly, is a growing public health problem with enormous impact on morbidity, mortality and resource utilization. In this proposal we evaluate novel urinary biomarkers and their relationship to aging, decline in kidney function and clinical outcomes. We plan to develop: a novel paradigm to define the kidney’s aging process; a potential method for the early detection of chronic injury to the kidney; and ultimately novel targets for therapies to reduce the burden of chronic kidney disease in the elderly.