Jenni Miettinen1, Heikki Helin2, Mikko Pakarinen3, Hannu Jalanko4, Jouni Lauronen5. 1. Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland. Electronic address: jenni.v.miettinen@helsinki.fi. 2. Division of Pathology and Genetics, HUSLAB, Helsinki University Central Hospital, PL 400, 00029 HUS, Helsinki, Finland. 3. Department of Pediatric Surgery, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland. 4. Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland. 5. Histocompatibility Laboratory, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland.
Abstract
BACKGROUND: Early detection of chronic allograft injury is a major challenge after kidney transplantation (RTx) in adults and children. We correlated the expression of four immunohistochemical biomarkers, P-selectin glycoprotein ligand-1 (PSGL-1), vimentin, α-smooth muscle actin (α-SMA) and collagen IV, to the kidney graft histology and function in pediatric RTx patients. METHODS: We analyzed the histopathology and immunohistochemical stainings of 165 biopsies from 56 patients. Histopathology was scored according to Banff '05 classification and biomarker expression semiquantitatively. Glomerular filtration rate (GFR) was measured annually by (51)Cr-EDTA clearance. RESULTS: In protocol biopsies, the expression of all four biomarkers correlated with the interstitial fibrosis and tubular atrophy (IF/TA) changes, which increased during the first 36months after RTx. At the time of 18month biopsy, we observed the deterioration of GFR in patients with high (≥2) IF/TA score (50 vs. 68ml/min/1.73m(2), p=0.004) or collagen IV expression (45 vs. 65ml/min/1.73m(2), p=0.016). Intense stainings of IF/TA, collagen IV and vimentin are also associated with poor GFR at 36 and 48months, however, the biomarker scores revealed no additional predictive value for concomitant or late GFR compared to IF/TA score. Patients with high and low biomarker expressions showed no significant differences in annual deterioration of GFR, which declined on average 2.2ml/min/1.73m(2)/year over the 7years follow-up. CONCLUSIONS: Overall, the results suggest that traditional histopathology is a sufficient predictor for graft function, and the routine use of these histochemical markers as surrogates for graft function deterioration is questioned.
BACKGROUND: Early detection of chronic allograft injury is a major challenge after kidney transplantation (RTx) in adults and children. We correlated the expression of four immunohistochemical biomarkers, P-selectin glycoprotein ligand-1 (PSGL-1), vimentin, α-smooth muscle actin (α-SMA) and collagen IV, to the kidney graft histology and function in pediatric RTxpatients. METHODS: We analyzed the histopathology and immunohistochemical stainings of 165 biopsies from 56 patients. Histopathology was scored according to Banff '05 classification and biomarker expression semiquantitatively. Glomerular filtration rate (GFR) was measured annually by (51)Cr-EDTA clearance. RESULTS: In protocol biopsies, the expression of all four biomarkers correlated with the interstitial fibrosis and tubular atrophy (IF/TA) changes, which increased during the first 36months after RTx. At the time of 18month biopsy, we observed the deterioration of GFR in patients with high (≥2) IF/TA score (50 vs. 68ml/min/1.73m(2), p=0.004) or collagen IV expression (45 vs. 65ml/min/1.73m(2), p=0.016). Intense stainings of IF/TA, collagen IV and vimentin are also associated with poor GFR at 36 and 48months, however, the biomarker scores revealed no additional predictive value for concomitant or late GFR compared to IF/TA score. Patients with high and low biomarker expressions showed no significant differences in annual deterioration of GFR, which declined on average 2.2ml/min/1.73m(2)/year over the 7years follow-up. CONCLUSIONS: Overall, the results suggest that traditional histopathology is a sufficient predictor for graft function, and the routine use of these histochemical markers as surrogates for graft function deterioration is questioned.
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