Nephrology Dialysis Transplantation

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ISSN / EISSN : 09310509 / 14602385
Current Publisher: Oxford University Press (OUP) (10.1093)
Total articles ≅ 29,234
Google Scholar h5-index: 66
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Laura S Van Dam, Ebru Dirikgil, Edwin W Bredewold, Argho Ray, Jaap A. Bakker, Cees Van Kooten, Ton J Rabelink, Yoe K Onno Teng
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa066

Abstract:
Background The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI). Methods This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19+ B-cell status and relapses were assessed >2 years. Results Patients (31/110) relapsed within 2 years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n = 29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n = 49) and reappearance of PR3-ANCAs (n = 10) associated significantly with more relapses (37%, P = 0.002 and 50%, P = 0.002). Patients with incomplete B-cell depletion (n = 11) had significantly more relapses (54%) as compared with patients with B-cell depletion [n = 76 (26%), P = 0.02]. Also, patients with repopulation of B cells (n = 58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [n = 27 (15%), P = 0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation. Conclusions Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX.
Anthony Bonavia, Gregory Vece, Kunal Karamchandani
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa061

The publisher has not yet granted permission to display this abstract.
Naoki Takahashi, Haruyoshi Yoshida, Hideki Kimura, Kazuko Kamiyama, Tomomi Kurose, Hidehiro Sugimoto, Toshio Imura, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, et al.
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa074

The publisher has not yet granted permission to display this abstract.
Elisabet Van Loon, Evelyne Lerut, Henriette De Loor, Dirk Kuypers, Marie-Paule Emonds, Dany Anglicheau, Wilfried Gwinner, Marie Essig, Pierre Marquet, Maarten Naesens
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa096

The publisher has not yet granted permission to display this abstract.
Rasmus Dreier, Bahareh Abdolalizadeh, Camilla L Asferg, Lisbet R Hölmich, Niels H Buus, Julie L Forman, Ulrik B Andersen, Martin Egfjord, Majid Sheykhzade, Jørgen L Jeppesen
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa114

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Pascale Khairallah, Thomas L Nickolas
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa068

Marcelo Barreto Lopes, Angelo Karaboyas, Brian Bieber, Ronald L Pisoni, Sebastian Walpen, Masafumi Fukagawa, Anders Christensson, P. Evenepoel, Marisa Pegoraro, Bruce M Robinson, et al.
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa054

Abstract:
Background Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain. Methods We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion. Results Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90–1.40] for AUC > 0–0.5, 1.26 (95% CI 0.99–1.62) for AUC > 0.5–1, 1.44 (95% CI 1.11–1.86) for AUC > 1–2 and 2.03 (95% CI 1.53–2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target). Conclusions We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO’s recommendation of serial assessment of phosphorus to guide clinical decisions.
Nicholas C Chesnaye, Friedo W Dekker, Marie Evans, Fergus J Caskey, Claudia Torino, Maurizio Postorino, Maciej Szymczak, Chava L Ramspek, Christiane Drechsler, Christoph Wanner, et al.
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa095

The publisher has not yet granted permission to display this abstract.
Tineke Kraaij, Eline J Arends, Laura S Van Dam, Sylvia W A Kamerling, Paul L A Van Daele, Obbo W Bredewold, Argho Ray, Jaap A Bakker, Hans U Scherer, Tom J W Huizinga, et al.
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa117

Abstract:
Background Anti-CD20 B-cell depletion has not shown superior efficacy to standard immunosuppression in patients with systemic lupus erythematosus (SLE). Besides trial design, potential explanations are incomplete B-cell depletion in relation to substantial surges in B-cell-activating factor (BAFF). To improve B-cell targeting strategies, we conducted the first study in SLE patients aimed at investigating immunological effects and feasibility of combining rituximab (RTX; anti-CD20) and belimumab (BLM; anti-BAFF). Methods Reported is the long-term follow-up of a Phase 2 proof-of-concept study in 15 patients with SLE including 12 (80%) with lupus nephritis (LN). Results In 10/15 (67%) patients, a clinical response was observed by achievement of lupus low disease activity state, of which 8 (53%) continued treatment (BLM + ≤7.5 mg prednisolone) for the complete 2 years of follow-up. Five patients (33%) were referred to as ‘non-responders’ due to persistent LN, major flare or repetitive minor flares. Out of 12 LN patients, 9 (75%) showed a renal response including 8 (67%) complete renal responders. All anti-dsDNA+ patients converted to negative, and both anti-C1q and extractable nuclear antigen autoantibodies showed significant reductions. CD19+ B cells showed a median decrease from baseline of 97% at 24 weeks, with a persistent reduction of 84% up to 104 weeks. When comparing responders with non-responders, CD20+ B cells were depleted significantly less in non-responders and double-negative (DN) B cells repopulated significantly earlier. Conclusions Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. The observed immunological and clinical benefits in a therapy-refractory SLE population prompt further studies on RTX + BLM.
Carlos K H Wong, Tingting Wu, Simon K H Wong, Betty T T Law, Eleanor Grieve, Enders K W Ng, Olivia Wu, Cindy L K Lam
Nephrology Dialysis Transplantation; doi:10.1093/ndt/gfaa075

The publisher has not yet granted permission to display this abstract.
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