Table 2.
Interstitial Fibrosis Evaluation
| Method | Description | Measure | Ref.(s) |
|---|---|---|---|
| VA; “routine” | IF, inflammation, and glomerulopathy correlated with poor allograft outcome | By multivariate analysis, IF and inflammation lead to poorer survival (HR = 8.5, p < 0.0001); IF alone had less effect (HR = 4.8, p = not significant) | [200] |
| IA; TC (Masson), SR, and SMA IHC | IA and semi-quantitative assessments (VA) were performed on late allograft biopsies | IF by VA predicted Banff ’97 ci scores (p < 0.0001) and correlated with GFR, Cr, and urine total protein (r = − 0.48, p = 0.0007; r = 0.46, p = 0.0009; r= 0.51, 0.0009, respectively). Of IA methods, only SR- nonpolarized score correlated with GFR and urine total protein (r = −0.29, p = 0.05; r = 0.29, p = 0.05, respectively) | [14] |
| IA; TC (Masson) | IF IA correlates with serum Cr in IgA nephropathy and MPGN | IF occupied > 10% of the interstitium in all 10 cases and > 20% in 6 and IF IA correlated with serum Cr | [201] |
| IA; TC (Masson) | IA of IF in patients receiving cyclosporine | IF grade by IA correlated with worsened Cr clearance between 1 and 3 years | [10] |
| IA; TC (Light Green) | IF IA in patients randomized to cyclosporine or conversion to sirolimus | No difference in groups with respect to fibrosis but GFR improved significantly in the conversion group | [202] |
| IA; TC (Light green) | Quantitative IF in sequential renal biopsies | IF evolution correlated with eGFR | [11] |
| IA; SR and collagen | Renal IF correlates with presence of TGF-β, decorin, SMA, and interstitial collagens | In all samples with IF, TGF-β up-regulation was observed in combination with reduced decorin expression | [169, 203– 205] |
| IA; SR | SR IA predicted long-term renal allograft function | Cortical IF correlated with time to graft failure (r = 0.64, P < 0.001) at 6 months post transplant | [24] |
| IA; SR | SR IA predicted long-term renal allograft function | Positive correlation (r = 0.62, P<0.001) between SR fibrosis and decreased GFR | [7] |
| IA; SR | SR IA corresponded to light microscopic semiquantitative measurements (r = 0.439, P = 0.0003 overall and r = 0.704, P < 0.0001 for just baseline specimens) in kidney allografts | Semiquantitative methods correlated best with long-term graft function (serum Cr at 8 – 10 years (P = 0.010) and late graft loss (P = 0.0445) | [206] |
| IA; SR | IF in non-heart-beating donor kidneys and conventional heart-beating donor kidneys | No significant difference in IF between the two groups | [207] |
| IA; SR | IF scoring predicts survival in lupus nephritis | Fibrillary collagen was predictive of Cr doubling (P = 0.01) and relapse (P = 0.06) | [208] |
| IA; SR | IA-based application (Fibrosis HR) for IF and glomerular morphometry | Intra- and interoperator variability was present in manual segmentation of IF, mesangial matrix, and glomerular areas but interactive identification didn’t have this variability | [209] |
| IA; SR | IF measurements using digital imaging coupled with point counting correlated with GFR | Direct relationship between interstitial volume fraction and renal function (r2 = 0.54) | [8] |
| IA; SR | SR IF measurement combined with ultrasound measurements of renal artery resistance index helped predict “chronic allograft nephropathy” | Positive correlation (r = 0.62, P <0.001) between picroSR-stained cortical fractional IF volume and decreased GFR | [9] |
| IA; CIII IHC | IF measurements by a semiautomatic system correlate with GFR in protocol renal transplant biopsy specimens | Area fraction of collagen III IHC of > 40% @ 6 months associated with decreased GFR @ 24 months compared with ≤ 40% (r=−0.32, P=0.03) | [12] |
| IA; CIII IHC | IF measurements by a semiautomatic system correlate with GFR in protocol renal transplant biopsies | GFR correlated negatively with interstitial volume fraction @ 6 months (P = 0.05) | [13] |
| IA and VA; TC (Masson) | Cyclosporine (CsA) therapy effects on fibrosis IA | IF measured by IA was significantly higher in the CsA group only in renal allografts 6 months posttransplant (P < 0.04) | [210, 211] |
| IA and VA; CII IHC, TC, and SR | Comparison of CII IHC, TC, and SR IA | Collagen III IHC and VA of TC-stained slides correlated best with each other and with GFR | [6] |
CIII: Collagen III, Cr: creatinine, eGFR: estimated GFR, GFR: glomerular filtration rate, IHC: immunohistochemistry, IF: interstitial fibrosis, IA: Image analysis, MPGN: membranoproliferative glomerulonephritis, SMA: smooth muscle actin, SR: Sirius red, Ref(s): References, TC: Trichrome, TGF-β: transforming growth factor, VA: visual analysis.