{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:37:42Z","timestamp":1792823862813,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background and hypothesis<\/jats:title>\n Pentoxifylline is an inexpensive anti-inflammatory agent tested in diabetic kidney disease for four decades; prior meta-analyses report reduced albuminuria. Whether it is secure, extends to kidney function, or reaches hard outcomes is unclear; we hypothesized the surrogate evidence might be conclusive and the hard-outcome evidence not.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We reviewed randomized trials of oral pentoxifylline in diabetic kidney disease to June 2026, without language restriction. Co-primary surrogate outcomes were albuminuria (ratio of means) and glomerular filtration rate (GFR) change (mean difference); the primary hard outcome was end-stage kidney disease or death (risk ratio). We pooled with random-effects models, assessed risk of bias with RoB 2, and report a prediction interval and trial sequential analysis with every estimate.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Thirty-four studies were included, 32 contributing data. Albuminuria fell by about a third (ratio of means 0.69, 95% CI 0.50\u20130.94; 22 studies contributing 23 comparisons), but heterogeneity was extreme (I2 97%), the prediction interval 0.15\u20133.10, and only 53% of the required information had accrued, with no boundary crossed. Over\u00a0\u2265\u00a012 months, GFR changed 4.49 mL\/min\/1.73 m2 more favorably with pentoxifylline than with control (0.84\u20138.14; 5 studies contributing 5 comparisons); in two trials at low or some-concerns risk of bias it was 2.96 (-15.34 to 21.26), with 11% of the required information accrued. For end-stage kidney disease or death, 29 events in 6 studies contributing 7 comparisons gave a risk ratio of 0.90 (0.46\u20131.77), 3% of that required. Gastrointestinal adverse events were three times as common (3.00, 1.94\u20134.64); serious ones were not (0.83, 0.56\u20131.22).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Pentoxifylline reduces albuminuria, but the effect is heterogeneous, depends on which trials are counted, and may not reappear in a new trial. Kidney failure and death have scarcely been tested. The priority is an adequately powered, long-term trial reporting hard endpoints; gastrointestinal intolerance should be anticipated.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/ndt\/gfag244","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:42:59Z","timestamp":1792496579000},"source":"Crossref","is-referenced-by-count":0,"title":["Pentoxifylline for chronic kidney disease in people with diabetes: a meta-analysis of randomized trials"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"first","affiliation":[{"name":"Richard L. Roudebush VA Medical Center and Indiana University School of Medicine , Indianapolis ,","place":["IN"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-9948","authenticated-orcid":false,"given":"David J","family":"Leehey","sequence":"additional","affiliation":[{"name":"Edward Hines, Jr VA Hospital , Hines ,","place":["IL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4953-7795","authenticated-orcid":false,"given":"Sankar D","family":"Navaneethan","sequence":"additional","affiliation":[{"name":"Michael E. DeBakey VA Medical Center , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M","family":"Utzschneider","sequence":"additional","affiliation":[{"name":"VA Puget Sound Health Care System , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xing","sequence":"additional","affiliation":[{"name":"Hines VA Cooperative Studies Program Coordinating Center , Hines ,","place":["IL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Carlson","sequence":"additional","affiliation":[{"name":"Hines VA Cooperative Studies Program Coordinating Center , Hines ,","place":["IL"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,22]]},"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag244\/72303350\/gfag244.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfag244\/72303350\/gfag244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:52:20Z","timestamp":1792821140000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article\/doi\/10.1093\/ndt\/gfag244\/8971940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfag244","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"article-number":"gfag244"}}