Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease.

Background: Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. Methods: We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. Results: A total of 329 CKD patients (243 men, mean age 60.3 ± 14.6 years) were included. Among them, 301 with an mGFR >15 ml/min/1.73 m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61 years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Conclusion: Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.

Conversion From Intravenous In-Hospital Belatacept Injection to Subcutaneous Abatacept Injection in Kidney Transplant Recipients During the First COVID-19 Stay-at-Home Order in France.

The first COVID-19 stay-at-home order came into effect in France on 17 March 2020. Immunocompromised patients were asked to isolate themselves, and outpatient clinic visits were dramatically reduced. In order to avoid visits to the hospital by belatacept-treated kidney transplant recipients (KTRs) during the initial period of the pandemic, we promptly converted 176 KTRs at two French transplant centers from once-monthly 5 mg/kg in-hospital belatacept infusion to once-weekly 125 mg subcutaneous abatacept injection. At the end of follow-up (3 months), 171 (97.16%) KTRs survived with a functioning graft, 2 (1.14%) had died, and 3 (1.70%) had experienced graft loss. Two patients (1.1%) experienced acute T cell-mediated rejection. Nineteen patients (10.80%) discontinued abatacept; 47% of the KTRs found the use of abatacept less restrictive than belatacept, and 38% would have preferred to continue abatacept. Mean eGFR remained stable compared to baseline. Seven patients (3.9%) had COVID-19; among these, two developed severe symptoms but survived. Only one patient had a de novo DSA. Side effects of abatacept injection were uncommon and non-severe. Our study reports for the first time in a large cohort that once-weekly injection of abatacept appears to be feasible and safe in KTRs previously treated with belatacept.

Impact of DSA and immunosuppression minimization on rejection, graft, and patient survival after simultaneous liver-kidney transplantation.

Background: Acute rejection rate is low after simultaneous liver-kidney transplantation (SLKT), leading some groups to minimize immunosuppressive (IS) regimens. However, the impact of preformed (pDSA) or de novo donor-specific antibodies (dnDSA) on the graft remains unclear. Methods: We performed a retrospective analysis of 102 consecutive SLKT patients to study the impact of anti-HLA antibodies. Results: Anti-HLA antibodies were detected in 75 recipients (class I 23.8%, both classes I and II 23.8%, and class II 14.3%). In total, 42.8% of the patients had pDSA and 21.7% developed dnDSA. Overall patient survival at 1-3 and 5 years, was respectively 88, 84, and 80%. Acute rejection occurred respectively in 3 (2.9%) liver and 6 kidney (5.9%) recipients. pDSA with titers over 10,000 mean fluorescence intensity (14.3%) was associated with lower patient survival (40 vs. 82%) but not with acute rejection. In a multivariable Cox regression analysis, the risk of death was associated with maleness, the highest titer of pDSA (p < 0.0007) or the sum of pDSA >10,000. Renal function did not differ between patients with class I pDSA (p = 0.631) and those with class II pDSA (p = 0.112) or between patients with and without a positive cross-match (p = 0.842). dnDSA were not associated with acute rejection, graft dysfunction or patient survival. IS minimization was not associated with rejection, graft dysfunction or death. Conclusion: In SLKT, high levels of pDSA >10,000 were associated with lower patient survival, but not rejection or graft survival. Minimization of maintenance immunosuppression regimen was not associated with a poorer outcome.

Co-stimulation Blockade Plus T-Cell Depletion in Transplant Patients: Towards a Steroid- and Calcineurin Inhibitor-Free Future?

Long-term survival of solid allografts depends on both immunosuppressive efficacy and reducing the side effects associated with these therapies. Immunotherapies developed over the past 15 years to prevent organ rejection have greatly improved cardiovascular and renal function compared with classical therapies, such as calcineurin inhibitors and corticosteroids. Immunotherapies that target T cells through the co-stimulation blockade (CTLA-4-Ig) improve renal function and the survival of grafts and patients, but are associated with higher rates of T-cell-mediated acute rejection. Improvements to safe and efficacious therapeutic options could combine a co-stimulation blockade with a depleting immunotherapy. Herein, we describe the clinical outcomes and the likely causes of defects in the co-stimulation blockade, and comment on new therapeutic strategies to overcome these. Great progress has been made to optimize immunotherapy using the co-stimulation blockade, but the therapeutic combinations should be assessed further.