Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.

Atypical hemolytic uremic syndrome is a prototypic thrombotic microangiopathy attributable to complement dysregulation. Hypertensive emergency, characterized by elevation of systolic (>180mmHg) or diastolic (>120mmHg) blood pressure together with end-organ damage, can cause thrombotic microangiopathy which may mimic atypical hemolytic uremic syndrome. We sought to retrospectively evaluate the clinical, biological and complement genetic characteristics of 76 and 61 atypical hemolytic uremic syndrome patients with and without hypertensive emergency, respectively. Patients with hypertensive emergency-hemolytic uremic syndrome were more frequently males, with neurological involvement, and a slightly higher hemoglobin level. At least one complement rare variant was identified in 51.3% (39/76) and in 67% (41/61) patients with or without hypertensive emergency, respectively (p=0.06). In both group, renal prognosis was severe with 23% and 40% of patients reaching end stage renal disease after a 5-year follow-up (p=0.1). The 5-year renal survival was 77% in patients without hypertensive emergency nor complement variant, and below 25% in the three groups of patients with hypertensive emergency and/or complement variant (p=0.02). In patients without hypertensive emergency, 5-year renal survival was 100% vs 40% with or without Eculizumab, respectively (p<0.001). Conversely, the 5-year renal survival of patients with hypertensive emergency was 46% vs 23% with or without Eculizumab, respectively (p=0.18). In conclusion, hypertensive emergency and complement rare variants are essential to stratify atypical hemolytic uremic syndrome long-term renal prognosis.

Background and objectives: Dialysis patients have a high mortality risk after coronavirus disease 2019 (COVID-19) and an altered immunologic response to vaccines, but vaccine clinical effectiveness remains unknown in this population. Design, setting, participants, & measurements: Using Bayesian multivariable spatiotemporal models, we estimated the association between vaccine exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severe infections (with hospital admission) in dialysis patients from simultaneous incidence in the general population. For dialysis patients, cases were reported within the French end-stage kidney disease REIN registry from March 11, 2020, to April 29, 2021, and vaccine exposure (first dose) was reported in weekly national surveys since January 2021. Cases in the general population were obtained from the national exhaustive inpatient surveillance system (SI-VIC database), and vaccination coverage (first dose) was obtained from the national surveillance system (VAC-SI database). Results: During the first wave, incidence in dialysis patients was approximately proportional to the general population. However, we showed a lower relative incidence for dialysis patients during the second wave (compared with that observed in nondialysis patients), suggesting an effect of prevention measures. Moreover, from the beginning of the vaccination rollout, incidence in dialysis patients was lower compared with predictions based on the first and second waves. Adding vaccination coverages in dialysis and nondialysis patients as predictors allowed the reported cases to be fit correctly (3685 predicted cases, 95% confidence interval, 3552 to 3816, versus 3620 reported). Incidence rate ratios were 0.37 (95% confidence interval, 0.18 to 0.71) for vaccine exposure in dialysis patients and 0.50 (95% confidence interval, 0.40 to 0.61) per 10% higher in vaccination coverage in the same-age general population, meaning that vaccine exposure in dialysis patients and the general population was independently associated with lower hospitalization rate of dialysis patients. Conclusions: Our findings suggest that vaccination may yield a protective effect against severe forms of COVID-19 in dialysis patients, despite altered immunologic vaccine responses.

Little is known about clinical characteristics and kidney outcome in patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in a context of inflammatory bowel disease (IBD). We conducted a retrospective multicenter study with centralized histological review, to analyze the presentation, therapeutic management and outcome of 24 patients suffering from IBD associated IgAN relative to a cohort of 134 patients with primary IgAN without IBD. Crohn’s disease and ulcerative colitis accounted for 75% and 25% of IBD-associated IgAN cases, respectively. IBD was diagnosed before IgAN in 23 cases (a mean of 9 years previously) and was considered active at IgAN onset in 23.6% of patients. Hypertension was present in 41.7% of patients. Urinary protein-to-creatinine ratio exceeded 100 mg/mmol in 70.8% of patients (mean: 254 mg/mmol). Estimated glomerular filtration rate (eGFR) exceeded 60 ml/min/1.73m² in 13/24 patients and only one patient required dialysis. In the Oxford MEST-C classification of renal biopsies, 57% were M1, 48% E1, 76% S1, 57% T1+T2 and 38% C1+C2. Steroids were administered in 50% of cases. After a mean follow-up of 7.2 years, four patients (16.7%) had a poor kidney outcome: end-stage renal disease (n = 3) or a > 50% decrease in eGFR from initial values (n = 1). A similar evolution was observed in patients with primitive IgAN. This first case series suggests that IBD-associated IgAN have frequent inflammatory lesions at onset and variable long-term outcome.

Background and objectives: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti–SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2–recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking. Design, setting, participants, & measurements: We evaluated the dynamics of antireceptor binding domain IgG titers and antireceptor binding domain memory B cells until 6 months after two and three doses (administered within 6 months after the second dose) of mRNA vaccine in SARS-CoV-2–recovered and virus-naive dialysis populations. Results were analyzed by ordinary one-way ANOVA, the Kruskal–Wallis test, or the Wilcoxon matched-pairs test as appropriate. Results: In total, 108 individuals (59 patients on dialysis and 49 controls) were included. In virus-naive patients on dialysis, antireceptor binding domain IgG response was quantitatively lower after two doses compared with healthy controls, but IgG titers increased by three-fold after three doses (P=0.008). In SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain IgG titers after two doses were significantly higher compared with virus-naive patients on dialysis but did not significantly increase after a third dose. Regarding memory B cell response, we detected receptor binding domain–specific memory B cells at similar proportions in virus-naive patients on dialysis and vaccinated controls after two doses. Moreover, a strong receptor binding domain–specific memory B cell expansion was observed after the third dose in virus-naive patients on dialysis (5.5-fold; P<0.001). However, in SARS-CoV-2–recovered patients on dialysis, antireceptor binding domain memory B cells remained unchanged after the third dose. Conclusions: The third dose of mRNA vaccine given within 6 months after the second dose boosts serologic and memory response in virus-naive patients but not in SARS-CoV-2–recovered patients on dialysis. Clinical Trial registry name and registration number: COVID-19: SARS-CoV-2 Specific Memory B and T-CD4+ Cells (MEMO-COV2), NCT04402892