Table 4.
Summary of papers dealing with posttransplantation kidney graft biopsy
| Author, year | Type of digital pathology | Number of patients/biopsies | Type of biopsy | Intervention | Controls or comparisons | Outcomes/Aim of the study | Results |
|---|---|---|---|---|---|---|---|
| Ito etal., 1994 | Static LM | 22 | Graft liver and kidney biopsy | Telepathology diagnosis | Direct LM diagnosis | Descriptive results | Agreement in 10/12 kidney biopsies and in 9/10 liver biopsies |
| Gandaliano etal., 1997 | LM plus DIA | 20 | Graft kidney biopsy | DIA assessment of IHC staining for CD68 and MCP-1 in acute rejection biopsies | DIA assessment of IHC staining for CD68 and MCP-1 in tubular damage and control biopsies | Descriptive differences in expression between groups and correlation with graft outcome | MCP-1 expression significantly higher in acute rejection biopsies |
| Grimm etal., 1999 | LM plus DIA | 32 | Graft kidney biopsy | DIA assessment of IHC staining of cellular infiltrate in clinical and subclinical rejection biopsies | DIA assessment of IHC staining of cellular infiltrate in normal controls | Descriptive differences in IHC staining among the groups | Significantly higher infiltration of CD8 and CD68 positive cells in clinical rejection |
| Nicholson etal., 1999 | LM plus DIA | 52 | Graft kidney biopsy | Semiautomatic DIA assessment of interstitial fibrosis with IHC | None | Descriptive correlation of interstitial fibrosis with graft outcome | Positive correlation of interstitial fibrosis as stained area with eGFR |
| Bonsib etal., 2000 | LM plus DIA | 14 (42 biopsies) | Graft kidney biopsy | Tubular membrane breaks with methenamine silver assessed on digital images | None | Descriptive correlation with clinical parameters | Correlation of tubular membrane breaks with creatinine level |
| Furukuwa etal., 2001 | LM plus DIA | 21 | Graft kidney biopsy | DIA software assessment of interstitial fibrosis | None | Descriptive correlation of degree of interstitial fibrosis with graft outcome | Usefulness of the computerized imaging diagnosis for quantitative evaluation of interstitial fibrosis in predicting graft failure |
| Ishimura etal., 2001 | LM plus DIA | 21 | Graft kidney biopsy | DIA software assessment of interstitial fibrosis | None | Descriptive correlation between interstitial fibrosis and TGF=beta IHC staining | Strong association between extracellular TGF beta expression and long-term decline in graft function and increased interstitial fibrosis |
| Ito etal., 2001 | Static LM | 31 (37 biopsies) | Graft kidney biopsy | Telepathology diagnosis | Direct LM diagnosis | Descriptive results | Agreement on diagnosis in 30/37cases |
| Minervini etal., 2001 | Static LM | 102 | Various case types, among which 9 kidney graft biopsies | Consultant telepathology review | Referring pathologist original diagnosis | Agreement rates, descriptive | 86% agreement and 14%(only 3% major) disagreement between referring and consultant pathologist |
| Danilewicz etal., 2003 | LM plus DIA | 34 | Graft kidney biopsy | DIA assessment of IHC staining and glomerular area in biopsies with acute rejection | DIA assessment of IHC staining and glomerular area in normal controls | Descriptive differences in IHC staining between the two groups | Significantly higher cellular infiltrate, glomerular area and interstitial area in acute rejection biopsies |
| Encarnacion etal., 2003 | LM plus DIA | 49 | Graft kidney biopsy | Different computerized strategies of DIA | Expert pathologist with LM | Correlation of tubulointerstitial fibrosis with graft function | Different degree of correlation with graft function of tubulointerstitial fibrosis scored with different strategies |
| Grimm etal., 2003 | LM plus DIA | NA | Graft kidney biopsy | Automated DIA software assessment of interstitial fibrosis | None | Correlation of interstitial fibrosis with graft outcome | Cortical fractional interstitial fibrosis volume can be a surrogate for time to graft failure |
| Mui etal., 2003 | LM plus DIA | 30 | Graft kidney biopsy | DIA assessment of IHC staining in ischemic injury | DIA assessment of IHC staining in normal controls | Descriptive | Different pattern of expression of markers in ischemic injury biopsies |
| Pape etal., 2003 | LM plus DIA | 56 | Graft kidney biopsy | DIA assessment of interstitial fibrosis | None | Correlation of interstitial fibrosis with graft outcome | Quantitative measurement of fibrosis by picrosirius red staining is a prognostic indicator for estimating long-term graft function |
| Sugiyama etal., 2003 | LM plus DIA | 25 | Graft kidney biopsy | DIA assessment of mean glomerular area and interstitial area | None | Descriptive differences in recipients with or without focal segmental glomerulosclerosis | No significant difference in mean glomerular area nor interstitial area between the two groups |
| Bains etal., 2004 | LM plus DIA | 112 | Graft kidney biopsy | DIA software assessment of fibrosis in DCD and DBD graft biopsies | None | Difference of fibrosis in the two groups | No significant differences in level of fibrosis |
| Danilewicz etal., 2004 | LM plus DIA | 35 | Graft kidney biopsy | DIA quantification of mast cells and leukocytes with IHC staining in acute rejection biopsies | DIA quantification of mast cells and leukocytes with IHC staining in normal controls | Descriptive differences between the groups | Significantly higher number of mast cells and leukocytes in acute rejection; positive correlation between inflammatory infiltrate and interstitial area |
| Pape etal., 2004 | LM plus DIA | 56 | Graft kidney biopsy | Renal resistance index with Doppler | Interstitial fibrosis assessment with DIA | Correlation between the two measurements and with graft outcome | Positive correlation between the two measures and of the combination of the two with graft outcome |
| Sarioglu etal., 2004 | LM plus DIA | 15 | Graft kidney biopsy | Automated quantification of stained area | None | Descriptive | Strong correlation between stained area and serum creatinine(r=0.64) |
| Sund etal., 2004 | LM plus DIA | 33 | Graft kidney biopsy | DIA automated quantification | Pathologist with LM | Descriptive | Significant correlation between the two modalities and with graft outcome |
| Nishi etal., 2005 | LM plus DIA | 14 | Graft kidney biopsy | DIA software assessment of the peritubular capillary network in recipients with rejection | DIA software assessment of the peritubular capillary network in recipients without rejection | Descriptive | Significant differences in surface areas of tubulin and glomerular diameter between the groups |
| Sis etal., 2005 | LM plus DIA | 57 (75 biopsies) | Graft kidney biopsy | DIA software assessment of stained area | None | Descriptive correlation among stained areas for fibrosis, Banff scores and rejection | No significant association between serum creatinine at time of biopsy and percentage of stained areas for fibrosis; no predictive value for rejection |
| Danilewicz etal., 2006 | LM plus DIA | 33 | Graft kidney biopsy | DIA of IHC staining in acute rejection recipients | DIA of IHC staining in recipients with no rejection | Differences in IHC staining in the two groups | Higher expression of TGF beta, CD3, CD8 in acute rejection |
| Hoffman etal., 2006 | LM plus DIA | 138 | Graft kidney biopsy | DIA of IHC staining | None | Descriptive expression of CXCR3 | Higher expression of CXCR3 in acute rejection |
| Lauronen etal., 2006 | LM plus DIA | 35 | Graft kidney biopsy | DIA software scoring | Pathologist with LM | Descriptive | No significant difference in scoring between the modalities |
| Roos-van- Groningen etal., 2006 | LM plus DIA | 54 (108 biopsies) | Graft kidney biopsy | Cyclosporine | Tacrolimus | Fibrosis and IHC staining assessed by automated DIA software | No quantitative differences in fibrosis and IHC staining between cyclosporine and tacrolimus |
| Rowshani etal., 2006 | LM plus DIA | 126 | Graft kidney biopsy | Cyclosporine | Tacrolimus | Fibrosis with Sirius red assessed by automated DIA software | No difference in the degree of interstitial stained area between the two treatment groups |
| Sarioglu etal., 2006 | LM plus DIA | 37 (44 biopsies) | Graft kidney biopsy | DIA assessment of periodic acid methenamine silver staining | None | Descriptive relation of stained area to Banff scores and creatinine values | Strong association of stained area with increased interstitial fibrosis and tubular atrophy Banff scores |
| Scholten etal., 2006 | LM plus DIA | 126 | Graft kidney biopsy | Cyclosporine | Tacrolimus | Subacute rejection assessed by pathologist and automated fibrosis quantification | No quantitative differences in fibrosis between cyclosporine and tacrolimus; higher prevalence of subacute rejection in the cyclosporine group but no difference in graft survival |
| Servais etal., 2007 | LM plus DIA | 26 | Graft kidney biopsy | DIA automated quantification of interstitial fibrosis in recipients treated with cyclosporine | None | Descriptive correlation of interstitial fibrosis with graft outcome | Correlation of higher grade of automated interstitial fibrosis with a higher creatinine |
| Servais etal., 2007 | LM plus DIA | 26 | Graft kidney biopsy | DIA automated quantification of interstitial fibrosis in recipients treated with cyclosporine | None | Descriptive correlation of interstitial fibrosis with graft outcome | Association between high grade of automated interstitial fibrosis and worsening of creatinine clearance |
| Birk etal., 2010 | LM plus DIA | 29 (105 biopsies) | Graft kidney biopsy | DIA software quantification of interstitial fibrosis | None | Descriptive correlation of interstitial fibrosis and graft outcome | Significant correlation of interstitial fibrosis assessed by DIA software with graft outcome |
| Yan etal., 2010 | LM plus DIA | 46 | Graft kidney biopsy | DIA quantification of IHC staining | None | Correlation of IHC staining with Banff score for interstitial fibrosis and tubular atrophy | Higher IHC staining expression in higher Banff score classes for interstitial fibrosis and tubular atrophy |
| Brazdziute etal., 2011 | WSI plus DIA | 32 (34 biopsies) | Graft kidney biopsy | Automated software on WSI | Pathologist on LM | Correlation and interobserver variability in C4d scoring | Good-to-high correlation between pathologist and automated software; good manual-automated interobserver agreement |
| Meas-Yedid etal., 2011 | WSI plus DIA | 90 biopsies | Graft kidney biopsy | Automated software on WSI | Expert pathologist on LM | Correlation and interobserver variability in interstitial fibrosis scoring | Good agreement between the two methods(κ=0.75) |
| Miura etal., 2011 | LM plus DIA | 109 | Graft kidney biopsy | DIA software assessment of interstitial fibrosis | None | Correlation of interstitial fibrosis different tacrolimus regimens and cytochrome polymorphism | Higher increase in interstitial fibrosis in absence of cytochrome polymorphism |
| Servais etal., 2011 | LM plus DIA | 140 | Graft kidney biopsy | Automated DIA software assessment of interstitial fibrosis | None | Correlation of interstitial fibrosis with graft outcome | Correlation between interstitial fibrosis at different time points and eGFR |
| Becker etal., 2012 | LM plus DIA | 40 | Graft kidney biopsy | IHC staining in cellular infiltrate of clinical, operational tolerance recipients | IHC staining in cellular infiltrate of rejection recipients | Descriptive expression of IHC staining in inflammatory infiltrate | Different IHC staining in the two groups |
| Ozluk etal., 2012 | WSI | 40 | Graft kidney biopsy | Pathologists with WSI | Pathologists with LM | Intra- and inter-observer reproducibility | Comparable intraobserver reproducibility for both modalities; higher interobserver reproducibility with WSI |
| Yan etal., 2012 | LM plus DIA | 28 | Graft kidney biopsy | DIA software quantification of IHC staining of GSK3 beta at different levels of inflammation | None | Descriptive correlation between GSK3 beta staining and inflammation | Stronger GSK3 beta expression with increasing grade of inflammation or interstitial fibrosis/tubular atrophy |
| Yan etal., 2012 | LM plus DIA | 61 | Graft kidney biopsy | DIA software quantification of IHC staining in recipients with AMR | DIA software quantification of IHC staining in recipients without AMR | Descriptive relationship of IHC staining of extracellular matrix cytokines with interstitial fibrosis and creatinine | Higher expression in grafts with AMR; increasing expression with higher Banff scores of interstitial fibrosis and positive correlation with creatinine |
| Caplin etal., 2013 | LM plus DIA | 246 | Graft kidney biopsy | Serial posttransplant biopsies | No serial biopsies | Descriptive correlation of index of chronic damage with graft function | No significant differences between the two groups; index of chronic damage not predictive of graft function |
| Jen etal., 2013 | WSI | 25 | Graft kidney biopsy | Expert pathologists with WSI | Expert pathologist with LM | Intra- and inter-observer concordance | Substantial intraobserver concordance between modalities (κ=0.60), moderate interobserver concordance (κ=0.41-0.45) |
| Farris etal., 2014 | WSI plus DIA | 30 | Graft kidney biopsies | Pathologists scoring interstitial fibrosis on WSI slides with different stains | Computerized DIA of collagen IHC staining | Interobserver reproducibility and correlation of visual assessment on WSI with DIA assessment and with graft outcome | Poor reproducibility between pathologists; moderate correlation of visual assessment with DIA assessment of collagen-IHC; moderate correlation with graft outcome with no significant differences between the modalities |
| Vuiblet etal., 2015 | LM plus DIA plus spectroscopy (FTIR) | 106 (166 biopsies) | Graft kidney biopsy | Spectroscopy | Pathologist with LM and DIA | Quantification of interstitial fibrosis and inflammation | Poor agreement between scoring LM versus DIA and LM versus FTIR, good agreement in percentages between DIA and FTIR; good correlation between fibrosis with FTIR and graft function |
| Hara etal., 2016 | LM plus DIA | 934 | Graft and native kidney biopsy | 426 graft biopsy | 508 native kidney biopsy | Quantification of GSECs | Prevalence of GSECs slightly increased with posttransplant duration but not statistically significant |
| Yan etal., 2016 | LM plus DIA | 50 | Graft kidney biopsy | DIA software assessment of IHC staining in graft with chronic dysfunction | DIA software assessment of IHC staining in graft with no dysfunction | Difference in markers expression and correlation with Banff scores for interstitial fibrosis/tubular atrophy | Higher expression in grafts with dysfunction; positive correlation between marker expression and Banff scores |
| Bräsens etal., 2017 | WSI plus DIA | 67 | Graft kidney biopsy | Automated software on WSI | None | Correlation of different cellular types digitally quantified with graft function | Predictive value of digitally quantified CD68 cell density for graft function |
| Moon etal., 2017 | WSI plus DIA | 45 | Graft kidney biopsy | DIA automated software assessment of interstitial inflammation with different algorithms | Visual assessment of interstitial inflammation | Descriptive correlation among the modalities | Quantitation algorithms correlated between each other and also with visual assessment |
AMR: Antibody-mediated rejection, DBD: Donor after brain death, DCD: Donor after cardiac death, DIA: Digital image analysis, eGFR: Estimated glomerular filtration rate, FTIR: Fourier-transformed infrared spectroscopy, GSECs: Granular swollen epithelial cells, IHC: Immunohistochemistry, LM: Light microscopy, WSI: Whole-slide imaging, MCP-1: Monocyte chemotactic peptide-1, TGF: Transforming growth factor