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Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosistubular atrophy (IFTA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IFTA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n 80), SCR (n 17), IFTA (n 42) and IFTA SCR (n 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IFTA SCR; normal (137 ± 117), SCR (202 ± 145), IFTA (208 ± 151) and IFTA SCR (307 ± 180 cellsmm2), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95 confidence interval: 1.23-7.35; p 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 ± 117), SCR (202 ± 145), IF/TA (208 ± 151) and IF/TA + SCR (307 ± 180 cells/mm2), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23–7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death‐censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 μmol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow‐up was 91 ± 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11–3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38–3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long‐term graft survival is modulated by SCR.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 μmol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 ± 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11–3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38–3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 μmol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 ± 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11–3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38–3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

Long-term consequences of glomerular enlargement after transplantation are not well understood. The aim is to evaluate the relationship between glomerular volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg and Banff chronic damage score were evaluated in protocol biopsies at 4 months. Creatinine clearance (CrCl) was estimated by the Cockroft-Gault formula. Vg estimated in 144 patients was 4.8 ± 2.0 × 106μ3. It was associated with donor age (r = 0.23, p < 0.01), recipient body mass index (r = 0.17, p = 0.04), delayed graft function (Vg = 5.9 ± 2.3 vs. 4.6 ± 1.9 × 106μ3, p < 0.01) and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score and CrCl was determined by Cox regression analysis, being 5.0 × 106μ3 for Vg (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03–5.6), >2 for chronic damage score (RR: 3.4, 95% CI: 1.03–8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI: 1.04–11.9). These variables were independent predictors of death-censored graft survival. According to Vg and CrCl, four groups of patients were defined. Patients with small glomeruli and high CrCl had a 95% graft survival while patients with large glomeruli and low CrCl had a 45% graft survival at 15 years (p < 0.01). Large glomerular volume, high Banff chronic score and poor early renal function in stable grafts are independently associated with death-censored graft survival.

Long‐term consequences of glomerular enlargement after transplantation are not well understood. The aim is to evaluate the relationship between glomerular volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg and Banff chronic damage score were evaluated in protocol biopsies at 4 months. Creatinine clearance (CrCl) was estimated by the Cockroft‐Gault formula. Vg estimated in 144 patients was 4.8 ± 2.0 × 106μ3. It was associated with donor age (r = 0.23, p < 0.01), recipient body mass index (r = 0.17, p = 0.04), delayed graft function (Vg = 5.9 ± 2.3 vs. 4.6 ± 1.9 × 106μ3, p < 0.01) and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score and CrCl was determined by Cox regression analysis, being 5.0 × 106μ3for Vg (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03–5.6), >2 for chronic damage score (RR: 3.4, 95% CI: 1.03–8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI: 1.04–11.9). These variables were independent predictors of death‐censored graft survival. According to Vg and CrCl, four groups of patients were defined. Patients with small glomeruli and high CrCl had a 95% graft survival while patients with large glomeruli and low CrCl had a 45% graft survival at 15 years (p < 0.01). Large glomerular volume, high Banff chronic score and poor early renal function in stable grafts are independently associated with death‐censored graft survival.