SARS-CoV-2 Antibody Response After a Third Dose of the BNT162b2 Vaccine in Patients Receiving Maintenance Hemodialysis or Peritoneal Dialysis.

RATIONALE & OBJECTIVE: Recent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared with the general population, suggesting the possible value of a third booster dose. We characterized the humoral response after 3 doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD). STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 69 French patients (38 HD and 31 PD) treated at a single center who received 3 doses of the BNT162b2 vaccine. FINDINGS: Humoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least 3 weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 years [interquartile range (IQR), 53-76 years], 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7,554 [IQR, 2,268-11,736] AU/mL after the third dose. Three patients were nonresponders (anti-S1 antibody level < 0.8 AU/mL), and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, 1 of the 3 initial nonresponders produced anti-spike antibody, and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe after a third vaccine dose. LIMITATIONS: Observational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood. CONCLUSIONS: A third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

Epithelial phenotypic changes detect cyclosporine in vivo nephrotoxicity at a reversible stage.

BACKGROUND: A widely used immunosuppressant, cyclosporine A (CsA), conveys long-term nephrotoxicity in some patients. However, no specific marker is presently available. In both native and transplanted human kidneys, epithelial phenotypic changes (EPCs) suggestive of epithelial to mesenchymal transition (EMT) are expressed in various diseases and are prognostic with respect to progression of interstitial fibrosis. We hypothesized that CsA is able to trigger these EPCs in tubular cells in vivo. METHODS: We studied the kinetics of the EMT markers ß-catenin, snail, vimentin, collagen III, and HSP47 at the messenger RNA and protein levels in the kidneys from rats injected with 15 mg/kg/day of CsA or its vehicle. We investigated several therapeutic strategies available to block EMT in this model. RESULTS: By 2 weeks, CsA had induced histological changes (tubular dilatation and vacuoles) and overexpression of EMT-related genes. This up-regulation of the EMT program was associated with tubular, not interstitial, overexpression of mesenchymal markers. Angiotensin II and endothelin receptor antagonists failed to prevent this CsA-induced EMT. Interestingly, CsA withdrawal led to the gradual regression of histological lesions and EMT, demonstrating that it not only prevents progression but also allows healing of renal injury. CONCLUSION: Our study suggests that detecting EPC could help to identify ongoing renal CsA-induced toxicity at an early and reversible stage.