{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:18:25Z","timestamp":1783487905222,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Interstitial fibrosis and tubular atrophy (IFTA) is an important pathological feature of diabetic kidney disease (DKD). Its prognostic value in biopsy-proven DKD remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study, 164 patients with type 2 diabetes and biopsy-confirmed pure DKD were followed for a median of 38 months. The primary composite kidney endpoint was initiation of kidney replacement therapy or kidney-related death. Predictors were selected using LASSO Cox regression. Random survival forest was used as an exploratory complementary analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-four patients reached the composite kidney endpoint. After LASSO selection and multivariable adjustment, IFTA score 2\/3 (vs. IFTA score 1, HR 3.96, 95%, CI 1.71\u20139.16,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.001), 24-hour proteinuria (per 1 g\/day increase; HR 1.52, 95%, CI 1.19\u20131.94,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;\u00a00.001), and lower serum calcium (per 1 mmol\/L increase; HR 0.140, 95% CI 0.041\u20130.481,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.002) were independently associated with the composite kidney endpoint. In the random survival forest analysis, serum calcium, baseline eGFR, and IFTA were among the most important variables. Patients with IFTA 2\/3 had significantly lower kidney survival than those with IFTA 1 (log-rank\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.0056).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In biopsy-proven DKD, IFTA 2\/3 was associated with the composite kidney endpoint. Higher 24-hour proteinuria and lower serum calcium were associated with poor kidney outcomes. Further studies are needed to confirm these findings and clarify their clinical implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1854787","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:53Z","timestamp":1783486433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic significance of interstitial fibrosis and tubular atrophy in biopsy-proven diabetic kidney disease: a single-center retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Key Laboratory of Kidney Disease Pathogenesis Research and Transformation Application, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The People\u2019s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture","place":["Kaili, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The People\u2019s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture","place":["Kaili, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Key Laboratory of Kidney Disease Pathogenesis Research and Transformation Application, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Key Laboratory of Kidney Disease Pathogenesis Research and Transformation Application, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Key Laboratory of Kidney Disease Pathogenesis Research and Transformation Application, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Key Laboratory of Kidney Disease Pathogenesis Research and Transformation Application, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","volume-title":"IDF Diabetes Atlas. 11th Edition","year":"2025"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2005.01.008","article-title":"Tubular changes in early diabetic nephropathy","volume":"12","author":"Thomas","year":"2005","journal-title":"Adv Chronic Kidney Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2021.07.001","article-title":"Targeting the pathobiology of diabetic kidney disease","volume":"28","author":"Thomas","year":"2021","journal-title":"Adv Chronic Kidney Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"15018","DOI":"10.1016\/j.mpmed.2022.08.002","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2016.11.011","article-title":"The tubulointerstitial pathophysiology of progressive kidney disease","volume":"24","author":"Schnaper","year":"2017","journal-title":"Adv Chronic Kidney Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199811123392007","article-title":"Pathophysiology of progressive nephropathies","volume":"339","author":"Remuzzi","year":"1998","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.70098","article-title":"Tubular injury in diabetic kidney disease: Early diagnosis and intervention strategies","volume":"41","author":"Lv","year":"2025","journal-title":"Diabetes Metab Res Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1232790","article-title":"Advances in understanding and treating diabetic kidney disease: Focus on tubulointerstitial inflammation mechanisms","volume":"14","author":"Xu","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7860\/jcdr\/2024\/74216.20277","article-title":"Predictive ability of interstitial fibrosis and tubular atrophy scoring in determining the severity of diabetic kidney disease: A cross-sectional study","volume":"18","author":"Gopichand","year":"2024","journal-title":"J Clin Diagn Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s500992","article-title":"Development of predictive models for progression from diabetic kidney disease to end-stage renal disease in type 2 diabetes mellitus: A retrospective cohort study","volume":"18","author":"Hu","year":"2025","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016333","article-title":"Histologic predictors of renal outcome in diabetic nephropathy: Beyond renal pathology society classification","volume":"98","author":"Stefan","year":"2019","journal-title":"Med (Baltimore)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.12.002","article-title":"Validation of the interstitial fibrosis and tubular atrophy on the new pathological classification in patients with diabetic nephropathy: A single-center study in China","volume":"30","author":"Zhu","year":"2016","journal-title":"J Diabetes Complications"},{"key":"B14","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s12882-021-02510-y","article-title":"Impact of the relationship between hemoglobin levels and renal interstitial fibrosis on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy","volume":"22","author":"Shimizu","year":"2021","journal-title":"BMC Nephrol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-023-02433-y","article-title":"Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy","volume":"28","author":"Fukata","year":"2024","journal-title":"Clin Exp Nephrol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1177\/09612033231151597","article-title":"Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation","volume":"32","author":"Rodelo","year":"2023","journal-title":"Lupus"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/txd.0000000000001375","article-title":"The progression of interstitial fibrosis and tubular atrophy at 6 months is an independent predictor of poor graft outcomes in kidney transplant recipients","volume":"8","author":"Ouellet","year":"2022","journal-title":"Transplant Direct"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/s41419-018-1157-x","article-title":"Renal tubular epithelial cells: The neglected mediator of tubulointerstitial fibrosis after injury","volume":"9","author":"Qi","year":"2018","journal-title":"Cell Death Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.350","article-title":"Chronic hypoxia as a mechanism of progression of chronic kidney diseases: From hypothesis to novel therapeutics","volume":"74","author":"Fine","year":"2008","journal-title":"Kidney Int"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-017-0423-9","article-title":"A more tubulocentric view of diabetic kidney disease","volume":"30","author":"Zeni","year":"2017","journal-title":"J Nephrol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12237349","article-title":"Pathomechanisms of diabetic kidney disease","volume":"12","author":"Sinha","year":"2023","journal-title":"J Clin Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00721.x","article-title":"The tubulointerstitium in progressive diabetic kidney disease: More than an aftermath of glomerular injury","volume":"56","author":"Gilbert","year":"1999","journal-title":"Kidney Int"},{"key":"B23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41574-025-01171-3","article-title":"Mechanisms of diabetic kidney disease and established and emerging treatments","volume":"22","author":"Martinez Leon","year":"2026","journal-title":"Nat Rev Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/jci72271","article-title":"Molecular mechanisms of diabetic kidney disease","volume":"124","author":"Reidy","year":"2014","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1020443","article-title":"Early renal structural changes and potential biomarkers in diabetic nephropathy","volume":"13","author":"Liu","year":"2022","journal-title":"Front Physiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2006","article-title":"Properties of the glomerular barrier and mechanisms of proteinuria","volume":"88","author":"Haraldsson","year":"2008","journal-title":"Physiol Rev"},{"key":"B27","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1042\/cs20210625","article-title":"Mechanisms of podocyte injury and implications for diabetic nephropathy","volume":"136","author":"Barutta","year":"2022","journal-title":"Clin Sci (Lond)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5148","DOI":"10.1038\/s41598-018-23500-5","article-title":"Lower serum calcium is independently associated with CKD progression","volume":"8","author":"Janmaat","year":"2018","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1186\/s40001-025-03277-w","article-title":"Dysregulation of mineral metabolism: Association of albumin-corrected calcium and vitamin D with diabetic kidney disease in type 2 diabetes-a cross-sectional study","volume":"30","author":"Ma","year":"2025","journal-title":"Eur J Med Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"21513","DOI":"10.1038\/s41598-024-72747-8","article-title":"Association of serum calcium levels with diabetic kidney disease in normocalcemic type 2 diabetes patients: A cross-sectional study","volume":"14","author":"Yu","year":"2024","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcdhc.2022.826383","article-title":"Effects of smoking on diabetic nephropathy","volume":"3","author":"Gundogdu","year":"2022","journal-title":"Front Clin Diabetes Healthc"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00194.2020","article-title":"Nicotine, smoking, podocytes, and diabetic nephropathy","volume":"320","author":"Jaimes","year":"2021","journal-title":"Am J Physiol Renal Physiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-018-1197-9","article-title":"The association between cigarette smoking and diabetic nephropathy in Chinese male patients","volume":"55","author":"Han","year":"2018","journal-title":"Acta Diabetol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1854787\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:54:07Z","timestamp":1783486447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1854787\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":33,"alternative-id":["10.3389\/fendo.2026.1854787"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1854787","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1854787"}}