Trial of Pirfenidone to Prevent Progression in Chronic Kidney Disease

Summary

Kidney disease is a global health problem, affecting more than 10% of the world's population and more than half of adults over 70 years of age in the United States. Persons with kidney disease are at higher risk for cardiovascular disease, heart failure, physical function decline, and mortality. Kidney scarring is a dominant factor in the development of kidney disease. Our group has evaluated several tests to determine the severity of scarring without requiring kidney biopsies, using MRI imaging scans and evaluating markers of scarring that we can measure in the urine. In this study we will use these measures to evaluate pirfenidone as a promising potential new treatment for patients with kidney disease.

Timeline

Start

2020-10-26

Primary completion

2024-05

Completion

2024-12

Publications

• Background Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012 Jan 14;379(9811):165-80. doi: 10.1016/S0140-6736(11)60178-5. Epub 2011 Aug 15.
• Background Fried LF, Biggs ML, Shlipak MG, Seliger S, Kestenbaum B, Stehman-Breen C, Sarnak M, Siscovick D, Harris T, Cauley J, Newman AB, Robbins J. Association of kidney function with incident hip fracture in older adults. J Am Soc Nephrol. 2007 Jan;18(1):282-6. doi: 10.1681/ASN.2006050546. Epub 2006 Dec 13.
• Background Shlipak MG, Stehman-Breen C, Fried LF, Song X, Siscovick D, Fried LP, Psaty BM, Newman AB. The presence of frailty in elderly persons with chronic renal insufficiency. Am J Kidney Dis. 2004 May;43(5):861-7. doi: 10.1053/j.ajkd.2003.12.049.
• Background Kurella M, Chertow GM, Fried LF, Cummings SR, Harris T, Simonsick E, Satterfield S, Ayonayon H, Yaffe K. Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study. J Am Soc Nephrol. 2005 Jul;16(7):2127-33. doi: 10.1681/ASN.2005010005. Epub 2005 May 11.
• Background Molsted S, Prescott L, Heaf J, Eidemak I. Assessment and clinical aspects of health-related quality of life in dialysis patients and patients with chronic kidney disease. Nephron Clin Pract. 2007;106(1):c24-33. doi: 10.1159/000101481.
• Background Odden MC, Whooley MA, Shlipak MG. Depression, stress, and quality of life in persons with chronic kidney disease: the Heart and Soul Study. Nephron Clin Pract. 2006;103(1):c1-7. doi: 10.1159/000090112. Epub 2005 Dec 7.
• Background Hailpern SM, Melamed ML, Cohen HW, Hostetter TH. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol. 2007 Jul;18(7):2205-13. doi: 10.1681/ASN.2006101165. Epub 2007 Jun 6.
• Background King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18.
• Background Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010 Feb;19(2):275-83. doi: 10.1517/13543780903501539.
• Background Sharma K, Ix JH, Mathew AV, Cho M, Pflueger A, Dunn SR, Francos B, Sharma S, Falkner B, McGowan TA, Donohue M, Ramachandrarao S, Xu R, Fervenza FC, Kopp JB. Pirfenidone for diabetic nephropathy. J Am Soc Nephrol. 2011 Jun;22(6):1144-51. doi: 10.1681/ASN.2010101049. Epub 2011 Apr 21.
• Background Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007 Sep;2(5):906-13. doi: 10.2215/CJN.01050207. Epub 2007 Aug 16.
• Background Kline JA, Jimenez D, Courtney DM, Ianus J, Cao L, Lensing AW, Prins MH, Wells PS. Comparison of Four Bleeding Risk Scores to Identify Rivaroxaban-treated Patients With Venous Thromboembolism at Low Risk for Major Bleeding. Acad Emerg Med. 2016 Feb;23(2):144-50. doi: 10.1111/acem.12865. Epub 2016 Jan 14.
• Background Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
• Background Malhotra R, Craven T, Ambrosius WT, Killeen AA, Haley WE, Cheung AK, Chonchol M, Sarnak M, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT. Am J Kidney Dis. 2019 Jan;73(1):21-30. doi: 10.1053/j.ajkd.2018.07.015. Epub 2018 Oct 2.
• Background Ix JH, Biggs ML, Mukamal K, Djousse L, Siscovick D, Tracy R, Katz R, Delaney JA, Chaves P, Rifkin DE, Hughes-Austin JM, Garimella PS, Sarnak MJ, Shlipak MG, Kizer JR. Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study. J Am Soc Nephrol. 2015 Oct;26(10):2494-503. doi: 10.1681/ASN.2014070696. Epub 2015 Feb 5.
• Background Zhang WR, Craven TE, Malhotra R, Cheung AK, Chonchol M, Drawz P, Sarnak MJ, Parikh CR, Shlipak MG, Ix JH; SPRINT Research Group. Kidney Damage Biomarkers and Incident Chronic Kidney Disease During Blood Pressure Reduction: A Case-Control Study. Ann Intern Med. 2018 Nov 6;169(9):610-618. doi: 10.7326/M18-1037. Epub 2018 Oct 23.
• Background Kahan BC, Morris TP. Analysis of multicentre trials with continuous outcomes: when and how should we account for centre effects? Stat Med. 2013 Mar 30;32(7):1136-49. doi: 10.1002/sim.5667. Epub 2012 Oct 30.

Drugs

Indications