Conversion From Belatacept to Another Immunosuppressive Regimen in Maintenance Kidney-Transplantation Patients.

INTRODUCTION: During the coronavirus disease 2019 (Covid-19) pandemic, several physicians have questioned pursuing belatacept in kidney-transplant patients in order to reduce the risk of nosocomial transmission during the monthly infusion. The effect of the conversion from belatacept to another immunosuppressive regimen is underreported. The aim of the present retrospective study was to assess the effect on kidney function and the clinical outcome of the conversion from belatacept to another regimen. METHODS: We have identified 44 maintenance kidney transplantation patients from five French kidney transplantation centers who were converted from belatacept to another regimen either because of a complication (n = 28) or another reason (patients' request or belatacept shortage, n = 13). The follow-up after the conversion from belatacept was 27.5 ± 25.3 months. RESULTS: Overall, mean estimated glomerular filtration rate (eGFR) decreased from 44.2 ± 16 ml/min per 1.73 m2 at conversion from belatacept to 35.7 ± 18.4 ml/min per 1.73 m2 at last follow-up (P = 0.0002). eGFR significantly decreased in patients who had been given belatacept at transplantation as well as in those who had been converted to belatacept earlier. The decrease was less significant in patients who had stopped belatacept without having experienced any complications. Finally, eGFR decreased more severely in patients who were converted to calcineurin inhibitors (CNIs), compared to those who received mammalian target of rapamycin inhibitor (mTORi). Few patients also developed diabetes and hypertension. CONCLUSIONS: Thus, transplantation physicians should avoid stopping belatacept when not clinically required.

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

BACKGROUND: Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies. METHODS: This prospective pilot randomized French multicenter study aimed to compare anti-T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included. RESULTS: Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%-37.1%) and 18.8% (95% CI, 8.9%-37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%-34.8%) and 28.2% (95% CI, 14.2%-51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell-mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups. CONCLUSION: This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution.

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis.

BACKGROUND: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency. OBJECTIVES: To describe the various presentations and identify predictive factors of death in patients with CPX. METHODS: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days). RESULTS: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes. CONCLUSIONS: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.

Conversion to Belatacept in Maintenance Kidney Transplant Patients: A Retrospective Multicenter European Study.

BACKGROUND: The use of belatacept is not yet approved for maintenance in kidney transplant patients. This retrospective multicenter European study aimed to assess the efficacy and safety of conversion to belatacept in a large cohort of patients in a real-life setting and to identify the predictive factors for improved kidney function after the switch. METHODS: Two hundred nineteen maintenance kidney transplant patients from 5 European kidney transplant centers were converted to belatacept at 21.2 months (0.1-337.1 months) posttransplantation, mainly because of impaired kidney function. Thirty-two patients were converted to belatacept within the first 3 months posttransplantation. The mean duration of follow-up was 21.9 ± 20.2 months. RESULTS: The actuarial rate of patients still on belatacept-based therapy was 77.6%. Mean estimated glomerular filtration rate increased from 32 ± 16.4 at baseline to 38 ± 20 mL/min per 1.73 m (P < 0.0001) at last follow-up. Conversion to belatacept before 3 months posttransplantation was the main predictive factor for a significant increase in estimated glomerular filtration rate (of 5 and 10 mL/min per 1.73 m at 3 and 12 months after the switch, respectively). Eighteen patients (8.2%) presented with an acute rejection episode after conversion; 3 developed a donor-specific antibody. Overall efficacy and safety were good, including for the 35 patients that had a donor-specific antibody at conversion. CONCLUSIONS: The conversion to belatacept was effective, especially when performed early after transplantation.