The Assessing Long Term Outcomes in Living Kidney Donors (ALTOLD) multicenter/multisite study successfully enrolled 200 pairs of living kidney donors and equally healthy two-kidney controls starting in July 2006. ALTOLD measured iohexol glomerular filtration rate (GFR) and traditional cardiovascular disease (CVD) risk factors pre- and 6, 12, 24 and 36 months post-donation. ALTOLD continues to answer important questions regarding the safety and the science of living kidney donation not addressed in previous uncontrolled cross- sectional studies. Important preliminary short-term results include the fact that GFR (slopes) increased between 6 and 36 months in donors v. controls, and that serum parathyroid hormone and uric acid levels have increased in donors v. controls. It is critically important to maintain these valuable cohorts to continue measuring trends in GFR and traditional CVD risk factors, and address new questions. The current proposal will conduct 6-year and begin 9-year follow-up visits. Long-term follow up will allow us to confirm the safety of kidney donation, and allow us to address a number of important scientific questions that have broad implications in our understanding of chronic kidney disease (CKD). ALTOLD will help determine whether the abnormalities associated CKD in observational studies are the cause or the result of the CKD. ALTOLD will test the hypothesis that GFR declines with age in normal, healthy individuals, and that unilateral nephrectomy accelerates this decline (Aim 1). It will also test the hypothesis that mild reductions in kidney function lead to chronic changes in mineral and bone disorders and other key CKD biomarkers in kidney donors (Aim 2). Finally, ALTOLD will test the hypothesis that mild declines in GFR affect arterial compliance (Aim 3). Specifically ALTOLD will measure aortic pulse wave velocity, which has been shown to correlate with CVD in patients with CKD, as well as small and large artery elasticity using applanation tonometry at the 6-year visit in both donors and controls. In summary, it is critical to capitalize on the short term investment in ALTOLD with uninterrupted long-term follow up that will minimize participant dropout and maximize the knowledge we will gain from this valuable cohort.

Public Health Relevance

Previous studies have examined the effects of living kidney donation on donors, but have failed to compare donors to individuals with two kidneys who are equally healthy. As a result, some important effects of kidney donation could have gone undetected. The current study proposes to continue testing kidney function and heart disease risk in a group of kidney donors who have been paired with healthy two-kidney controls over an extended period of time.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
4U01DK066013-10
Application #
9135319
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Kimmel, Paul
Project Start
2003-12-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
10
Fiscal Year
2016
Total Cost
$671,091
Indirect Cost
$84,807
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Ryan, Zachary C; Craig, Theodore A; Wang, Xuewei et al. (2018) 1?,25-dihydroxyvitamin D3 mitigates cancer cell mediated mitochondrial dysfunction in human skeletal muscle cells. Biochem Biophys Res Commun 496:746-752
Tebben, Peter J; Singh, Ravinder J; Kumar, Rajiv (2016) Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment. Endocr Rev 37:521-547
Ryan, Zachary C; Craig, Theodore A; Folmes, Clifford D et al. (2016) 1?,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells. J Biol Chem 291:1514-28
Kasiske, Bertram L; Anderson-Haag, Teresa; Israni, Ajay K et al. (2015) A prospective controlled study of living kidney donors: three-year follow-up. Am J Kidney Dis 66:114-24
Ahearn, Aaron J; Parekh, Justin R; Posselt, Andrew M (2015) Islet transplantation for Type 1 diabetes: where are we now? Expert Rev Clin Immunol 11:59-68
Ryan, Zachary C; Craig, Theodore A; Filoteo, Adelaida G et al. (2015) Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3. Biochem Biophys Res Commun 467:152-6
Lam, Ngan N; Lentine, Krista L; Levey, Andrew S et al. (2015) Long-term medical risks to the living kidney donor. Nat Rev Nephrol 11:411-9
Kumar, Rajiv; Vallon, Volker (2014) Reduced renal calcium excretion in the absence of sclerostin expression: evidence for a novel calcium-regulating bone kidney axis. J Am Soc Nephrol 25:2159-68
Kasiske, Bertram L; Anderson-Haag, Teresa; Ibrahim, Hassan N et al. (2013) A prospective controlled study of kidney donors: baseline and 6-month follow-up. Am J Kidney Dis 62:577-86