Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had DSA. Compared with patients with preexisting DSA ABMR, patients with DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. DSA ABMR was characterized by increased expression of IFN-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the DSA ABMR (63% versus 34% at 8 years after rejection, respectively;<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identified DSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08;=0.03); low eGFR (<30 ml/min per 1.73 m) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23; <0.001); ≥0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09; <0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79; =0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients for DSA.

BackgroundTransplant glomerulopathy, a common glomerular lesion observed after kidney transplant that is associated with poor prognosis, is not a specific entity but rather the end stage of overlapping disease pathways. Its heterogeneity has not been precisely characterized to date.MethodsOur study included consecutive kidney transplant recipients from three centers in France and one in Canada who presented with a diagnosis of transplant glomerulopathy (Banff cg score ≥1 by light microscopy), on the basis of biopsies performed from January of 2004 through December of 2014. We used an unsupervised archetype analysis of comprehensive pathology findings and clinical, immunologic, and outcome data to identify distinct groups of patients.ResultsAmong the 8207 post-transplant allograft biopsies performed during the inclusion period, we identified 552 biopsy samples (from 385 patients) with transplant glomerulopathy (incidence of 6.7%). The median time from transplant to transplant glomerulopathy diagnosis was 33.18 months. Kidney allograft survival rates at 3, 5, 7, and 10 years after diagnosis were 69.4%, 57.1%, 43.3%, and 25.5%, respectively. An unsupervised learning method integrating clinical, functional, immunologic, and histologic parameters revealed five transplant glomerulopathy archetypes characterized by distinct functional, immunologic, and histologic features and associated causes and distinct allograft survival profiles. These archetypes showed significant differences in allograft outcomes, with allograft survival rates 5 years after diagnosis ranging from 88% to 22%. Based on those results, we built an online application, which can be used in clinical practice on the basis of real patients.ConclusionsA probabilistic data-driven archetype analysis approach applied in a large, well defined multicenter cohort refines the diagnostic and prognostic features associated with cases of transplant glomerulopathy. Reducing heterogeneity among such cases can improve disease characterization, enable patient-specific risk stratification, and open new avenues for archetype-based treatment strategies and clinical trials optimization.

BackgroundAustralia has unrestricted access to direct-acting antivirals (DAA) for hepatitis C virus (HCV) treatment. In order to increase access to treatment, primary care providers are able to prescribe DAA after fibrosis assessment and specialist consultation. Transient elastography (TE) is recommended prior to commencement of HCV treatment; however, TE is rarely available outside secondary care centres in Australia and therefore a requirement for TE could represent a barrier to access to HCV treatment in primary care.ObjectivesIn order to bridge this access gap, we developed a community-based TE service across the Sunshine Coast and Wide Bay areas of Queensland.DesignRetrospective analysis of a prospectively recorded HCV treatment database.InterventionsA nurse-led service equipped with two mobile Fibroscan units assesses patients in eight locations across regional Queensland. Patients are referred into the service via primary care and undergo nurse-led TE at a location convenient to the patient. Patients are discussed at a weekly multidisciplinary team meeting and a treatment recommendation made to the referring GP. Treatment is initiated and monitored in primary care. Patients with cirrhosis are offered follow-up in secondary care.Results327 patients have undergone assessment and commenced treatment in primary care. Median age 48 years (IQR 38–56), 66% male. 57% genotype 1, 40% genotype 3; 82% treatment naïve; 10% had cirrhosis (liver stiffness >12.5 kPa). The majority were treated with sofosbuvir-based regimens. 26% treated with 8-week regimens. All patients had treatment prescribed and monitored in primary care. Telephone follow-up to confirm sustained virological response (SVR) was performed by clinic nurses. 147 patients remain on treatment. 180 patients have completed treatment. SVR data were not available for 19 patients (lost to follow-up). Intention-to-treat SVR rate was 85.5%. In patients with complete data SVR rate was 95.6%.ConclusionCommunity-based TE assessment facilitates access to HCV treatment in primary care with excellent SVR rates.

Background Little is known about clinical characteristics and kidney outcome in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). Methods We conducted a retrospective multicenter study with centralized histological review, to analyze the presentation, therapeutic management and outcome of 24 patients suffering from IBD associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. Results Crohn’s disease and ulcerative colitis accounted for 75% and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. Urinary protein-to-creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean: 254 mg/mmol). Estimated glomerular filtration rate (eGFR) exceeded 60 ml/min/1.73m2 in 13/24 patients and only one patient required dialysis. In the Oxford MEST-C classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1+T2 and 38% C1+C2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, four patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a &gt; 50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN. Conclusions This first case series suggests that IBD-associated IgAN have frequent inflammatory lesions at onset and variable long-term outcome.