Background and objectivesActivation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease.MethodsWe conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival.ResultsOf the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26–64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298–977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr).ConclusionIn patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p < 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.

Immune checkpoint inhibitors (CPIs) have opened a new era in the treatment of cancer, and their indications are increasing rapidly. To date, these CPIs include anti-CTLA4 (ipilimumab), anti-Programmed Death 1 (PD1) (nivolumab, pembrolizumab) and anti-Programmed Death-Ligand 1 (PD-L1) (atezolizumab, avelumab, durvalumab) antibodies (Abs). Solid organ transplant recipients have a higher risk of neoplastic complications because of immunosuppressive treatments and oncogenic viral infections [ [1] Engels E.A. Pfeiffer R.M. Fraumeni Jr., J.F. Kasiske B.L. Israni A.K. Sydner J.J. et al. Spectrum of cancer risk among US solid organ transplant recipients. J Am Med Assoc. 2011; 306: 1891-1901 Crossref PubMed Scopus (985) Google Scholar ]. Thus, cancer has now become the second cause of death among transplant patients [ [2] Buell J.F. Gross T.G. Woodle E.S. Malignancy after transplantation. Transplantation. 2005; 80: S254-S264 Crossref PubMed Scopus (477) Google Scholar ]. However, data are lacking regarding the use of CPI in these transplant patients because they were excluded from clinical trials because of the theoretical risk of organ rejection [ 3 Postow M.A. Chesney J. Pavlick A.C. Robert C. Grossman K. McDermott C. et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2010; 372: 2006-2017 Crossref Scopus (2098) Google Scholar , 4 Borghaei H. Paz-Ares L. Horn L. Spigel D.R. Steins M. Ready N.E. et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015; 373: 1627-1639 Crossref PubMed Scopus (6769) Google Scholar , 5 Ansell S.M. Lesokhin A.M. Borrello I. Halwani A. Scott E.C. Gutierrez M. et al. PD 1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015; 372: 311-319 Crossref PubMed Scopus (2635) Google Scholar ]. Only a few isolated cases of CPI use in transplant recipients have been reported in the literature so far (reviewed in [ [6] Kittai A.S. Oldham H. Cetnar J. Taylor M. Immune checkpoint Inhibitors in organ transplant patients. J Immunother. 2017; 40: 277-281 Crossref PubMed Scopus (94) Google Scholar ]). Therefore, although there is a clear medical need, the possibility of using these new therapies in transplant patients with cancer remains largely unknown. Here, we report a series of seven kidney allograft recipients treated with CPI for cancer.

Checkpoint inhibitors as anti-Cytotoxic T Lymphocyte-Associated protein 4 (CTLA-4) and anti-Programmed Cell Death Protein 1 (PD-1) agents are proven effective in metastatic melanoma, non-small-cell lung cancer and renal cell carcinoma.1 However their efficacy and safety in solid organ transplant recipients are not defined. We report an ex-smoker 64-years-old white male who developed a end-stage chronic kidney disease due to acute renal ischemia in 2006. He underwent deceased-donor kidney transplantation (KT) in 2009 (HLA-mismatches : A1, B1, DR2, DQ2). Initial immmunosuppresive therapies included tacrolimus (FK), mycophenolate mofetil (MMF) and prednisone. He had no history of rejection episode. This article is protected by copyright. All rights reserved.