{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:01:48Z","timestamp":1791223308178,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K08 DK110429-01"],"award-info":[{"award-number":["K08 DK110429-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX003025"],"award-info":[{"award-number":["BX003025"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK110871"],"award-info":[{"award-number":["R01 DK110871"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Impaired musculoskeletal health in individuals with CKD reduces their ability to participate in activities and quality of life, and increases the risk of illness, injury, and death. Exercise studies in animals or people with CKD have produced inconsistent results about the potential benefits on the musculoskeletal system and few studies have examined the systemic effects of exercise in CKD. The authors show that 10 weeks of voluntary wheel running in rats with CKD improved multiple systems, including mineral metabolism, left ventricular mass, physical function, and bone health. The results suggest physical activity may help patients with CKD, but further studies are needed to establish the most efficacious modalities and optimal dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy\/+\n                      <jats:sub>IU<\/jats:sub>\n                      ) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2\u20133 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO\n                      <jats:sub>2max<\/jats:sub>\n                      ), body composition and bone micro-CT and mechanics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Wheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO\n                      <jats:sub>2max<\/jats:sub>\n                      ), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Voluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2019040349","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T13:45:14Z","timestamp":1568036714000},"page":"1898-1909","source":"Crossref","is-referenced-by-count":21,"title":["Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)"],"prefix":"10.1681","volume":"30","author":[{"given":"Keith G.","family":"Avin","sequence":"first","affiliation":[{"name":"Division of Nephrology and"},{"name":"Department of Physical Therapy, Indiana University School of Health and Human Sciences, Indianapolis, Indiana; and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Allen","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Anatomy and Cell Biology, and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal X.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalisha D.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley D.","family":"Troutman","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Indiana University School of Health and Human Sciences, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrison","family":"Mast","sequence":"additional","affiliation":[{"name":"Anatomy and Cell Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Swallow","sequence":"additional","affiliation":[{"name":"Anatomy and Cell Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Indiana University School of Health and Human Sciences, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Anatomy and Cell Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0540","authenticated-orcid":false,"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Medicine and General Surgery, Indiana University School of Medicine, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Warden","sequence":"additional","affiliation":[{"name":"Anatomy and Cell Biology, and"},{"name":"Department of Physical Therapy, Indiana University School of Health and Human Sciences, Indianapolis, Indiana; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon M.","family":"Moe","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"},{"name":"Anatomy and Cell Biology, and"},{"name":"Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ki.2008.456","article-title":"A rat model of chronic kidney disease-mineral bone disorder","volume":"75","author":"Moe","year":"2009","journal-title":"Kidney Int"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/ndt\/gfn613","article-title":"Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease","volume":"24","author":"Covic","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.2215\/CJN.09500916","article-title":"Fractures in patients with CKD: Time for action","volume":"11","author":"Moe","year":"2016","journal-title":"Clin J Am Soc Nephrol"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1681\/ASN.2012070702","article-title":"Association between physical performance and all-cause mortality in CKD","volume":"24","author":"Roshanravan","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/cphy.c110025","article-title":"Lack of exercise is a major cause of chronic diseases","volume":"2","author":"Booth","year":"2012","journal-title":"Compr Physiol"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1053\/j.ajkd.2014.03.020","article-title":"Exercise training in adults with CKD: A systematic review and meta-analysis","volume":"64","author":"Heiwe","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000156715","article-title":"Effect of exercise on cardiac tissue oxidative and inflammatory mediators in chronic kidney disease","volume":"29","author":"Bai","year":"2009","journal-title":"Am J Nephrol"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1152\/japplphysiol.00344.2014","article-title":"Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease","volume":"117","author":"Kuczmarski","year":"2014","journal-title":"J Appl Physiol (1985)"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1249\/01.MSS.0000159006.87769.67","article-title":"Voluntary exercise during chronic renal failure in rats","volume":"37","author":"Adams","year":"2005","journal-title":"Med Sci Sports Exerc"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"F418","DOI":"10.1152\/ajprenal.00014.2014","article-title":"Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease","volume":"307","author":"Martens","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"B11-20231016","first-page":"19","article-title":"Effects of treadmill running in a rat model of chronic kidney disease","volume":"16","author":"Organ","year":"2018","journal-title":"Biochem Biophys Rep"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/ng.2681","article-title":"ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3","volume":"45","author":"Hoff","year":"2013","journal-title":"Nat Genet"},{"key":"B13-20231016","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ki.2015.122","article-title":"The SAM domain of ANKS6 has different interacting partners and mutations can induce different cystic phenotypes","volume":"88","author":"Bakey","year":"2015","journal-title":"Kidney Int"},{"key":"B14-20231016","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/ki.1993.79","article-title":"Autosomal-dominant polycystic kidney disease in the rat","volume":"43","author":"Cowley","year":"1993","journal-title":"Kidney Int"},{"key":"B15-20231016","doi-asserted-by":"crossref","first-page":"e0159411","DOI":"10.1371\/journal.pone.0159411","article-title":"Skeletal muscle regeneration and oxidative stress are altered in chronic kidney disease","volume":"11","author":"Avin","year":"2016","journal-title":"PLoS One"},{"key":"B16-20231016","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/jbmr.2372","article-title":"Anti-sclerostin antibody treatment in a rat model of progressive renal osteodystrophy","volume":"30","author":"Moe","year":"2015","journal-title":"J Bone Miner Res"},{"key":"B17-20231016","doi-asserted-by":"crossref","first-page":"H1301","DOI":"10.1152\/ajpheart.2001.280.3.H1301","article-title":"Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy","volume":"280","author":"Wisl\u00f8ff","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.coph.2015.04.003","article-title":"Cachexia and sarcopenia: Mechanisms and potential targets for intervention","volume":"22","author":"Argil\u00e9s","year":"2015","journal-title":"Curr Opin Pharmacol"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/jbmr.2089","article-title":"A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD","volume":"29","author":"Moe","year":"2014","journal-title":"J Bone Miner Res"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000347031","article-title":"Transglutaminase 2 accelerates vascular calcification in chronic kidney disease","volume":"37","author":"Chen","year":"2013","journal-title":"Am J Nephrol"},{"key":"B21-20231016","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J Bone Miner Res"},{"key":"B22-20231016","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1007\/s00198-012-2103-x","article-title":"Skeletal effects of zoledronic acid in an animal model of chronic kidney disease","volume":"24","author":"Allen","year":"2013","journal-title":"Osteoporos Int"},{"key":"B24-20231016","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1249\/01.mss.0000183179.86594.4f","article-title":"Training effects in mice after long-term voluntary exercise","volume":"38","author":"Davidson","year":"2006","journal-title":"Med Sci Sports Exerc"},{"key":"B25-20231016","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1152\/jappl.1995.79.3.902","article-title":"Metabolic responses of rat respiratory muscles to voluntary exercise training","volume":"79","author":"Halseth","year":"1995","journal-title":"J Appl Physiol (1985)"},{"key":"B26-20231016","first-page":"E337","article-title":"Muscle protein turnover: Effects of exercise training and renal insufficiency","volume":"248","author":"Davis","year":"1985","journal-title":"Am J Physiol"},{"key":"B27-20231016","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/ki.1987.281","article-title":"Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy","volume":"32","author":"Heifets","year":"1987","journal-title":"Kidney Int"},{"key":"B28-20231016","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0272-6386(95)90119-1","article-title":"The impact of gender on the progression of chronic renal disease","volume":"25","author":"Silbiger","year":"1995","journal-title":"Am J Kidney Dis"},{"key":"B29-20231016","doi-asserted-by":"crossref","first-page":"H2768","DOI":"10.1152\/ajpheart.00292.2004","article-title":"Sex modifies exercise and cardiac adaptation in mice","volume":"287","author":"Konhilas","year":"2004","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B30-20231016","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1053\/j.ajkd.2013.02.368","article-title":"Trends in hip fracture rates in US hemodialysis patients, 1993-2010","volume":"62","author":"Arneson","year":"2013","journal-title":"Am J Kidney Dis"},{"key":"B31-20231016","doi-asserted-by":"crossref","first-page":"0108021","DOI":"10.1115\/1.4029176","article-title":"Biomechanics and mechanobiology of trabecular bone: A review","volume":"137","author":"Oftadeh","year":"2015","journal-title":"J Biomech Eng"},{"key":"B32-20231016","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/jbm4.10117","article-title":"Rethinking bone disease in kidney disease","volume":"2","author":"Damasiewicz","year":"2018","journal-title":"JBMR Plus"},{"key":"B33-20231016","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1007\/s00774-011-0278-4","article-title":"Soy protein diet and exercise training increase relative bone volume and enhance bone microarchitecture in a mouse model of uremia","volume":"29","author":"Tomayko","year":"2011","journal-title":"J Bone Miner Metab"},{"key":"B34-20231016","doi-asserted-by":"crossref","first-page":"F90","DOI":"10.1152\/ajprenal.00356.2018","article-title":"Aerobic interval exercise improves renal functionality and affects mineral metabolism in obese Zucker rats","volume":"316","author":"Mart\u00ednez","year":"2019","journal-title":"Am J Physiol Renal Physiol"},{"key":"B35-20231016","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/ndt\/gfv373","article-title":"Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats","volume":"31","author":"Troib","year":"2016","journal-title":"Nephrol Dial Transplant"},{"key":"B36-20231016","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1053\/j.jrn.2017.04.009","article-title":"Effect of aerobic exercise on markers of bone metabolism of overweight and obese patients with chronic kidney disease","volume":"27","author":"Gomes","year":"2017","journal-title":"J Ren Nutr"},{"key":"B37-20231016","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s11255-014-0662-9","article-title":"Positive association of vigorous and moderate physical activity volumes with skeletal muscle mass but not bone density or metabolism markers in hemodialysis patients","volume":"46","author":"Morishita","year":"2014","journal-title":"Int Urol Nephrol"},{"key":"B38-20231016","doi-asserted-by":"crossref","first-page":"e4134","DOI":"10.1097\/MD.0000000000004134","article-title":"Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients","volume":"95","author":"Liao","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"B39-20231016","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1093\/ndt\/gfp078","article-title":"R-568 reduces ectopic calcification in a rat model of chronic kidney disease-mineral bone disorder (CKD-MBD)","volume":"24","author":"Moe","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B40-20231016","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000444423","article-title":"Calcitriol suppression of parathyroid hormone fails to improve skeletal properties in an animal model of chronic kidney disease","volume":"43","author":"Newman","year":"2016","journal-title":"Am J Nephrol"},{"key":"B41-20231016","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bone.2012.10.013","article-title":"Mechanosensation and transduction in osteocytes","volume":"54","author":"Klein-Nulend","year":"2013","journal-title":"Bone"},{"key":"B42-20231016","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/j.cell.2018.10.025","article-title":"Irisin mediates effects on bone and fat via \u03b1V integrin receptors","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"B43-20231016","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41574-018-0151-9","article-title":"Irisin receptor in osteocytes identified","volume":"15","author":"Greenhill","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B44-20231016","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3390\/biomedicines5040062","article-title":"Muscle-bone crosstalk: Emerging opportunities for novel therapeutic approaches to treat musculoskeletal pathologies","volume":"5","author":"Maurel","year":"2017","journal-title":"Biomedicines"},{"key":"B45-20231016","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000101827","article-title":"Kidney function and sarcopenia in the United States general population: NHANES III","volume":"27","author":"Foley","year":"2007","journal-title":"Am J Nephrol"},{"key":"B46-20231016","doi-asserted-by":"crossref","first-page":"e0176230","DOI":"10.1371\/journal.pone.0176230","article-title":"Sarcopenia in patients with chronic kidney disease not yet on dialysis: Analysis of the prevalence and associated factors","volume":"12","author":"Souza","year":"2017","journal-title":"PLoS One"},{"key":"B47-20231016","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2019040349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:30:56Z","timestamp":1786131056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2019040349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,9]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2019040349","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,9]]}}}