IFTA Foci Density: An Unrecognized Highly Prognostic Measurement of Fibrosis in Kidney Transplant Biopsies.

Key Points: Morphometry allows for a more prognostic multidimensional quantification of interstitial fibrosis and tubular atrophy (IFTA) in kidneys than does visual inspection. The density of IFTA foci is determined by dividing the number of contiguous IFTA patches in the kidney cortex by the area of cortex. Higher density of IFTA foci significantly predicted renal allograft failure beyond %IFTA and other biopsy and clinical characteristics.

Background: Contraction of interstitial fibrosis and 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 CKD in native kidneys independent of %IFTA.

Methods: We studied kidney transplant recipients transplanted between 2000 and 2013 who had a 5-year surveillance kidney biopsy and subsequent follow-up. Banff 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 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 score (1.5 versus 0.7, < 0.0001), %IFTA (22.6% versus 7.0%, < 0.0001), and IFTA foci density (1.3/mm versus 0.4/mm, < 0.0001). After adjusting for other Banff scores or clinical variables, Banff did not correlate with allograft failure, but both higher %IFTA (hazard ratio = 1.56, < 0.0001) and higher IFTA foci density (hazard ratio = 2.34, < 0.0001) did. All but four 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.