title: Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study.
abstract: CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum solubleα-klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m2and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.
authors.affiliation: Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, Massachusetts; ddrew@tuftsmedicalcenter.org.
authors.forename: David A
authors.initials: DA
authors.lastname: Drew
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kritchevsky
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA and Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California.
authors.forename: Joachim
authors.initials: J
authors.lastname: Ix
authors.affiliation: Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, San Francisco, California; Departments of.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
authors.affiliation: Medicine and.|Epidemiology, University of Alabama School of Medicine, Birmingham, Alabama.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
authors.forename: Anne
authors.initials: A
authors.lastname: Newman
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
authors.forename: Andy
authors.initials: A
authors.lastname: Hoofnagle
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.|Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.|Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.|Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania and.
authors.forename: Linda
authors.initials: L
authors.lastname: Fried
authors.affiliation: Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.affiliation: Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Sarnak
mesh_terms: D000368:Aged; D000375:Aging; D001823:Body Composition; D005260:Female; D005966:Glucuronidase / Q000097:blood* / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D000090265:Klotho Proteins; D008297:Male; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: chronic kidney disease; kidney dysfunction; klotho; risk factors