Aleksandar Denic, Andrew D Rule, Walter D Park, Byron H Smith, Mateo Velasquez Meija, Aleksandra Kukla, Joseph P Grande, Mark D Stegall
{"title":"IFTA Foci Density: An Unrecognized Highly Prognostic Measurement of Fibrosis in Kidney Transplant Biopsies.","authors":"Aleksandar Denic, Andrew D Rule, Walter D Park, Byron H Smith, Mateo Velasquez Meija, Aleksandra Kukla, Joseph P Grande, Mark D Stegall","doi":"10.34067/KID.0000000000000514","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Contraction of interstitial fibrosis/tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive chronic kidney disease in native kidneys independent of %IFTA.</p><p><strong>Methods: </strong>We studied kidney transplant recipients transplanted between 2000-2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density.</p><p><strong>Results: </strong>There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 vs 0.7, p<0.0001), %IFTA (22.2% vs 7.0%, p<0.0001), and IFTA foci density (1.3 vs. 0.4 per mm2, p<0.001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (HR=1.56, p<0.0001) and higher IFTA foci density (HR=2.34, p<0.001) did. All but 4 allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure.</p><p><strong>Conclusions: </strong>Morphometric characterization of IFTA foci density is a strong predictor of death censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney360","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34067/KID.0000000000000514","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Contraction of interstitial fibrosis/tubular atrophy (IFTA) may cause %IFTA to under-represent the severity of nephron loss. Higher density of IFTA foci is an important predictor of progressive chronic kidney disease in native kidneys independent of %IFTA.
Methods: We studied kidney transplant recipients transplanted between 2000-2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff ci score (interstitial fibrosis) was obtained from the pathology reports. After digitizing the biopsies, we traced cortex area and each distinct IFTA focus on a single trichrome-stained section. Percent IFTA area and IFTA foci density (count of IFTA foci/cortex area) were calculated. Cox models assessed the risk of death-censored graft failure after the 5-year biopsy with Banff ci score, morphometric %IFTA, and IFTA foci density.
Results: There were 58 death-censored allograft failures among 835 kidney recipients during the 5 years of follow-up. Biopsies from grafts that failed had higher mean Banff ci score (1.5 vs 0.7, p<0.0001), %IFTA (22.2% vs 7.0%, p<0.0001), and IFTA foci density (1.3 vs. 0.4 per mm2, p<0.001). After adjusting for other Banff scores or clinical variables, Banff ci did not correlate with allograft failure, but both higher %IFTA (HR=1.56, p<0.0001) and higher IFTA foci density (HR=2.34, p<0.001) did. All but 4 allograft failures by 10 years had biopsies in the top quartile of either %IFTA or IFTA foci density at 5 years. A model using just these two morphometric measures without clinical characteristics resulted in a c-statistic of 0.891 with respect to allograft failure.
Conclusions: Morphometric characterization of IFTA foci density is a strong predictor of death censored allograft failure not captured in current Banff classification for grading of kidney fibrosis.