Assessment of active tubulointerstitial nephritis in non-scarred renal cortex improves prediction of renal outcomes in patients with IgA nephropathy.

BACKGROUND: The addition of tubulointerstitial inflammation to the existing pathological classification of IgA nephropathy (IgAN) is appealing but was previously precluded due to reportedly wide inter-observer variability. We report a novel method to score percentage of non-atrophic renal cortex containing active tubulointerstitial inflammation (ATIN) in patients with IgAN and assess its utility to predict clinical outcomes. METHODS: All adult patients with a native renal biopsy diagnosis of IgAN between 2010 and 2015 in a unit serving 1.5 million people were identified. Baseline characteristics, biopsy reports and outcome data were collected. ATIN was calculated by subtracting the percentage of atrophic cortex from the percentage of total cortex with tubulointerstitial inflammation, with ≥10% representing significant ATIN. The primary outcome was a composite of requiring renal replacement therapy or doubling of serum creatinine. RESULTS: In total 153 new cases of IgAN were identified, of which 111 were eligible for inclusion. Of these, 76 (68%) were male and 54 (49%) had ATIN on biopsy. During a median follow-up of 2.3 years, 34 (31%) reached the primary outcome. On univariable Cox regression analysis, ATIN was associated with a five-fold increase in the primary outcome [hazard ratio (HR) (95% confidence interval) 4.9 (95% confidence interval (CI) 2.1-11.3)]. On multivariable analysis, mesangial hypercellularity, tubular atrophy and interstitial fibrosis and ATIN independently associated with renal outcome (P = 0.02 for ATIN). Inter-observer reproducibility revealed fair agreement in the diagnosis of ATIN (κ=0.43, P = 0.05). CONCLUSIONS: Within our centre, ATIN was significantly associated with renal outcome in patients with IgAN, independently of established histological features and baseline clinical characteristics.

Early measurement of pulsatility and resistive indexes: correlation with long-term renal transplant function.

PURPOSE: To correlate pulsatility index (PI) and resistive index (RI) measured at early specific intervals after transplantation with 1-year estimated glomerular filtration rate (eGFR) and death-censored transplant survival to assess the long-term prognostic value of these Doppler indexes. MATERIALS AND METHODS: The local ethics committee was consulted, and no formal approval was required. This retrospective review included 178 consecutive patients (111 male, 67 female; mean age, 43.9 years ± 13.4 [standard deviation]; age range, 16-72 years) undergoing first deceased-donor renal transplantation between 1997 and 2000. All patients were identified from a prospectively maintained database. Spectral Doppler analysis was performed within 1 week after transplantation in all patients and between 1 week and 3 months after transplantation in 124 patients. Average PI and RI were determined from measurements obtained in the upper, lower, and interpolar regions. For statistical analysis, the χ(2) test, analysis of variance, the Student t test, Kaplan-Meier survival plots, and Cox proportional hazards models were used. RESULTS: Within 1 week after transplantation, there was a significant association between PI and 1-year eGFR when analyzed as tertiles (P = .02). Between 1 week and 3 months after transplantation, there was a significant relationship between 1-year eGFR and both PI and RI when comparing the lowest and highest tertiles (47.5 mL/min/1.73 m(2) for PI <1.26 vs 32.7 mL/min/1.73 m(2) for PI >1.49 [P = .01], 42.8 mL/min/1.73 m(2) for RI <0.69 vs 32.3 mL/min/1.73 m(2) for RI >0.74 [P = .03]). Both PI and RI were independent predictors of death-censored transplant survival (hazard ratio, 1.68 per unit [P < .001] and 260.4 per unit, respectively [P = .02]). CONCLUSION: PI and RI in the early posttransplantation period correlate with long-term transplant function and can potentially be used as prognostic markers to aid risk stratification for future transplant dysfunction.

Management of cytomegalovirus infection by weekly surveillance after renal transplant: analysis of cost, rejection and renal function.

BACKGROUND: Recently published guidelines recommend anti-viral prophylaxis as the best method of preventing cytomegalovirus (CMV) disease in the post-transplant period, but some authors have suggested that surveillance strategies may be as effective and less costly. The aim of the present study was to analyse the effectiveness and cost of a deferred treatment strategy using weekly CMV polymerase chain reaction (PCR) surveillance in high risk renal transplant recipients. METHODS: We used weekly surveillance for plasma CMV PCR positivity for the first 3 months in consecutive renal transplants between CMV seropositive donors and seronegative recipients, and analysed incidence of CMV infection, timing of infection, acute rejection and renal function at 1 year. RESULTS: There was evidence of CMV infection in 27/41 (65.9%) patients and of CMV disease in 20/41 (48.8%). Only 8/20 (40%) patients were PCR positive before disease onset. Patients were treated on the basis of clinical evidence of CMV disease (deferred strategy), but we used the data to compare the potential costs of a pre-emptive strategy (all patients PCR positive before the onset of clinical features of disease treated with intravenous ganciclovir) and prophylaxis (oral ganciclovir for 3 months in all patients). The deferred strategy cost pound 1159 per patient (excluding the cost of hospitalization) while a pre-emptive strategy would cost pound 1381 per patient. Prophylaxis costs pound 1500- pound 2213 per patient depending on published estimates of relative risk reduction. Mean estimated creatinine clearance at 1 year was 70.0 ml/min in patients who experienced no infection, 47.7 ml/min in patients who experienced infection but no disease, and 39.6 ml/min in patients who experienced CMV disease (P < 0.001). The incidence of acute rejection in these groups was 7.1, 14.3 and 35%, respectively (P = 0.13). CONCLUSIONS: CMV surveillance strategies may cost slightly less but may have a deleterious effect on long-term outcome compared with prophylaxis.