Morphometric and Visual Evaluation of Fibrosis in Renal Biopsies

Abstract

Interstitial fibrosis is an outcome measure of increasing importance in clinical trials of both renal transplantation and native disease, but data on the comparative advantages of fibrosis measurement methods are limited. We compared four morphometric techniques and contrasted these with two visual fibrosis-scoring methods on trichrome-stained slides. Two morphometric methods included whole-slide digital images: collagen III immunohistochemistry and a new technique using trichrome and periodic acid-Schiff subtraction morphometry; the other two methods included Sirius Red with and without polarization on multiple digital fields. We evaluated 10 serial sections from 15 renal biopsies with a range of fibrosis extent and diagnoses on duplicate sections with each method on separate days. Three pathologists performed visual scoring on whole-slide images. Visual and morphometric techniques had good to excellent interassay reproducibility (R 2 ϭ 0.62 to 0.96) and interobserver reproducibility (R 2 ϭ 0.75 to 0.99, all P Ͻ 0.001). Morphometry showed less variation between observers than visual assessment (mean of 1% to 5% versus 11% to 13%). Collagen III, Sirius Red unpolarized, and visual scores had the strongest correlations (R 2 ϭ 0.78 to 0.89), the greatest dynamic range, and the best correlation with estimated GFR (R 2 ϭ 0.38 to 0.50, P Ͻ 0.01 to 0.001). Considering efficiency, reproducibility, and functional correlation, two current techniques stand out as potentially the best for clinical trials: collagen III morphometry and visual assessment of trichrome-stained slides.

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…At least one study offers reassurance that this is not the case (361). Protocol biopsies of the renal allograft may also provide important sequential information on renal fibrosis, in particular when evaluated quantitatively (362)(363)(364). Thus, biopsies obtained from renal transplant recipients at day 0 and month 3 and 12 showed a rapid progression of IF scores from 19% to 27% at month 3 and 32% at month 12 (363).…”

B lymphocytes in renal interstitial fibrosis

“…In renal allograft studies, the extent of interstitial fibrosis is used to prognosticate the life of an allograft (Farris et al 2011). Though it is not clear whether a causal relationship between fibrosis and chronic renal function loss exists (Mack and Yanagita 2015), a reciprocal correlation lies between kidney function and interstitial fibrosis extent (Farris et al 2011).…”

“…In renal allograft studies, the extent of interstitial fibrosis is used to prognosticate the life of an allograft (Farris et al 2011). Though it is not clear whether a causal relationship between fibrosis and chronic renal function loss exists (Mack and Yanagita 2015), a reciprocal correlation lies between kidney function and interstitial fibrosis extent (Farris et al 2011). In the past decade, the supposition that fibrosis is irreversible was challenged by a study that showed, in patients with diabetic nephropathy, the progression of chronic lesions could be repaired on pancreas transplantation (Fioretto et al 2006).…”

The Role of Glomerulosclerosis and Tubular Atrophy as Determining Factor for Reduced Kidney Function in Kidney Stone Disease

“…Those techniques are recommended and widely applied in the clinical setting. 18 Evaluation of renal function with estimated GFR are very important for the diagnosis and treatment of patients with CKD. Fomula Cockcroft -Gault and modification of diet renal disease formula (MDRD) are most commonly used with some limitations.…”