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.

Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review.

Our aim was to describe the main features of amyloid goiter in adults with amyloidosis secondary to familial Mediterranean fever. Therefore, we analyzed cases from a French cohort of familial Mediterranean fever patients with amyloidosis and from literature review. Forty-two cases were identified: 9 from the French cohort and 33 from literature review. Ninety percent of patients were on hemodialysis for renal amyloidosis before the development of goiter. The goiter grew up rapidly in 88% of cases; 75.6% of patients were euthyroid, 58% displayed dyspnea, and 44.8% dysphagia. Various features were seen on ultrasound, from diffuse to multinodular goiter. When it was performed, fine-needle aspiration biopsy almost always revealed amyloidosis. Thirty-one patients underwent thyroidectomy: to manage compressive symptoms (72%) or rule out malignancy (27%). Histology showed mature adipose tissue in 64% of cases and lymphocytic infiltration in 21.4%. In conclusion, amyloid goiter in familial Mediterranean fever preferentially occurs in patients with end stage renal failure. Fine-needle aspiration biopsy seems to be a sensitive exam for diagnosis, but thyroidectomy remains sometimes necessary to rule out malignancy or release compressive symptoms.

Rituximab alone as induction therapy for membranous lupus nephritis: A multicenter retrospective study.

The optimal treatment for pure membranous lupus nephritis (MLN) remains undetermined. Rituximab constitutes a promising therapeutic option for lupus nephritis and is currently being evaluated for use in idiopathic membranous nephritis. We retrospectively analysed the efficacy and tolerance of rituximab as a monotherapy in the induction treatment of pure MLN.We retrospectively investigated SLE patients with biopsy-proven pure class V lupus nephritis presenting with a protein-to-creatinine ratio of at least 2 g/g and treated with rituximab as monotherapy. A background low dose of corticosteroids (≤20 mg/day) was allowed, as was hydroxychloroquine; higher doses of steroids and/or immunosuppressive drugs fell under the exclusion criteria. Remission status was evaluated at baseline and 6, 12, and 24 months after rituximab.The study included 15 patients (13 women, median age 37 years, 27% with extra-renal manifestations, median SLE duration 1.5 years). The median protein-to-creatinine ratio was 4.9 g/g, 80% of the patients had nephrotic-range proteinuria, the median serum albumin was 24 g/L, the median serum creatinine was 0.7 mg/dL, and the median eGFR was 122 mL/min/1.73 m. The median follow-up was 29 months (6-112 months). Treatment failure occurred in 2 patients. However, remission was recorded in the remaining 13 (87%, complete remission in 8 patients) with a median time to remission of 5 months. Median proteinuria decreased from 4.9 g/g to 0.16 g/g at month 12 and to 0.11 g/g at month 24. Median serum albumin increased to 36.5 g/L at month 24, and all patients had serum albumin levels greater than 30 g/L at month 12. Renal function remained stable in all patients. Relapse of proteinuria was recorded in 3 patients (at 12, 29, and 34 months). No patients experienced serious adverse events.Rituximab as monotherapy may represent an effective treatment for pure MLN with an excellent tolerance profile.

Rituximab treatment for membranous nephropathy: a French clinical and serological retrospective study of 28 patients.

The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA(2)R antibodies in serum and PLA(2)R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27-50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate <45/ml/min/1.73 m(2)) is an independent factor that predicts lack of response to rituximab. Anti-PLA(2)R antibodies were detected in the serum of 10 patients, and PLA(2)R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.

A 59-kD renal antigen as a new target for rapidly progressive glomerulonephritis.

Anti-glomerular basement membrane (anti-GBM) antibodies are the hallmark of anti-GBM disease, which is characterized by rapidly progressive glomerulonephritis. We describe the case of a 58-year-old woman who presented with rapidly progressive glomerulonephritis with typical anti-GBM staining found by means of direct immunofluorescence microscopy, associated with linear immunoglobin G deposits on tubules. Serum analysis showed circulating anti-tubular basement membrane antibodies, but failed to detect anti-GBM antibodies. Immunoblotting showed that serum antibodies reacted with a 59-kd antigen found along both the GBM and tubular basement membrane.

Risk factors and outcome of focal and segmental glomerulosclerosis recurrence in adult renal transplant recipients.

BACKGROUND: Recurrence of nephrotic syndrome (NS) after renal transplantation for primary focal segmental glomerulosclerosis (FSGS) is a frequent and still unpredictable complication. However, risk factors for recurrence have not yet been clearly identified. METHODS: Data from 33 patients who underwent 35 renal transplantations for FSGS in two French centres are reported. RESULTS: Recurrent NS occurred in 12 transplant recipients (34%). A significantly higher number of patients in the group with recurrence (R group) compared with the group without recurrence (NR group) received cyclosporine for FSGS treatment before transplantation (83.3% vs 43.4%, P<0.02). Donors of R group recipients were significantly older than those of the non-NR group recipients (42.8 years vs 35 years, P<0.05). A higher number of patients from the R group required post-transplantation dialysis (33.3% vs 17.4%, P = 0.002). Surprisingly, acute rejection occurred more frequently in patients of the NR group compared with the R group, although the difference was not significant. Among the 12 patients with NS relapse, 9 were treated with plasmapheresis. Graft loss related to recurrence occurred in 6 cases. The 5-year graft survival was significantly lower in patients with recurrent NS compared with patients without recurrence (57% vs 82%, P<0.001). CONCLUSION: This study confirms the benefit to identify in the future clinical or biological predictive risk factors for NS recurrence after renal transplantation. It also indicates that donor age is a reliable risk factor for recurrence in adult recipients and suggests for the first time a possible opposite relationship between recurrent FSGS and acute rejection.

Acute graft pyelonephritis: a potential cause of acute rejection in renal transplant.

Acute graft pyelonephritis is a common complication in renal transplant recipients. The consequences of this complication on kidney allograft survival remain controversial. Bacterial infection is likely to activate the immune system, potentially leading to acute or chronic rejection. Here, we report for the first time two documented cases of acute rejection occurring shortly after acute graft pyelonephritis, suggesting that pyelonephritis can initiate acute rejection. The immunologic process leading to the alloimmune response is discussed. These reports suggest that acute rejection should be questioned in case of atypical graft outcome in the context of acute graft pyelonephritis.

Long-term benefit of mycophenolate mofetil in renal transplantation.

The results of clinical trials of mycophenolate mofetil (MMF) and the analysis of numerous data from renal transplant registries have shown that MMF reduces the incidence of early and late rejection (even in the black population), is protective against long-term deterioration of renal function, and reduces late renal allograft loss independently of acute rejection without increasing the risk for malignancies.