Background: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. Methods: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). Results: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (−15.9%; 95% CI, −29.4 to −2.5) compared with the PLEX not recommended group (−4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. Conclusions: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

Background: Hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. Methods: We conducted a retrospective study describing the kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed up in two university hospitals from the South of France between June 2011 and June 2021. Results: A total of 103 patients were included, among whom 79 were symptomatic and 24 were presymptomatic carriers. Patients carried 21 different ATTR mutations and 54% carried the V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.3% had a urinary protein:creatinine ratio ≥0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. The median CKD-free survival in symptomatic patients was estimated at 81.0 years (interquartile range 77.1–84.9). It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of the onset of CKD was 69.3 ± 13.0 years. In one 38-year-old V30M female who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. Conclusion: CKD affects almost one-third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.

Background: The French Renal Epidemiology and Information Network (REIN) is 20 years old. It is not just a national data registry, but rather an epidemiological and informational network serving patients with chronic kidney disease, nephrology teams and health services. Methods: The past 10-year trends of the incidence and prevalence of renal replacement therapy by dialysis or kidney transplantation and waitlist activity are presented. To detect potential significant changes in trends from 2012 and 2021, a Joinpoint regression model was used. Results: The overall incidence of treated end-stage kidney disease (ESKD) was 169 per million population (pmp) in 2021. It was stable despite an increase in the incidence of diabetes. We found a decreasing trend in the proportion of patients starting dialysis in an emergency but an increase in those starting haemodialysis (HD) with a temporary catheter. Peritoneal dialysis decreased by 1.7% each year, whereas home HD, although involving only 1% of dialysis patients, increased by 10% each year. For patients not treated at home, the median time to drive from the patient's home to the dialysis unit was 17 min. The proportion of patients on the transplantation waitlist at the start of dialysis increased from 7% to 12%. Among the 111 263 new ESKD patients from 2012 to 2021, 8% received a first transplant at 1 year and 20% at 5 years. Among kidney transplant recipients, the mean time on the waitlist increased from 13.8 to 22.6 months. Living donor transplants increased in frequency, representing 15% of kidney transplants. Conclusions: Data from the REIN registry allow for the evaluation of needs and provide a planning tool for French authorities. The progressive implementation of automatic data retrieval from dialysis informatics charts might alleviate the burden of data collection. Furthermore, the research activity the REIN engenders, resulting in renewed confidence by health authorities in the dynamism of French nephrology, allows for an optimistic outlook for the REIN.

Arteriovenous (AV) access complications remain a major cause of morbidity in hemodialysis patients, influenced by multiple factors, including endothelial inflammation induced by uremia. In this study, we investigated the mechanisms underlying the upregulation of endothelial chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) by indolic uremic toxins, as well as their association with AV access complications in hemodialysis patients. In cultured human endothelial cells, IL-8 and MCP-1 were upregulated by indolic uremic toxins through activation of their receptor, the aryl hydrocarbon receptor (AHR), and non-canonical TGF-β pathway involving TAK1/p38 MAPK/AP-1 signaling. In a retrospective observational study of 204 hemodialysis patients, baseline serum IL-8 or MCP-1 were positively correlated with indolic uremic toxins and TGFβ1. Additionally, serum IL-8 ≥ 40.26 pg/mL and serum MCP-1 were independently associated with an increased risk of AV access complications over a 2-year period. In conclusion, we demonstrated that indolic uremic toxins promote endothelial inflammation by inducing IL-8 and MCP-1 expression via AHR activation and non-canonical TGF-β signaling. Clinically, elevated serum IL-8 and MCP-1 were independently associated with an increased risk of AV access complications in hemodialysis patients.

Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) patients with severe microischemia. Interestingly, some studies showed that rheopheresis sessions improve endothelial function. Methods: Our study evaluated the inflammatory and endothelial biomarker evolution in 23 HD patients treated or not with rheopheresis. A p value ≤ 0.001 was considered statistically significant. Results: Thirteen HD patients treated by rheopheresis either for a severe peripheral arterial disease (N = 8) or calciphylaxis (N = 5) were analyzed. Ten control HD patients were also included in order to avoid any misinterpretation of the rheopheresis effects in regard to the HD circuit. In the HD group without rheopheresis, the circulating endothelial adhesion molecules, cytokines, angiogenic factor concentrations, and circulating levels were not modified. In the HD group with rheopheresis, the circulating endothelial adhesion molecules (sVCAM-1, sP-selectin, and sE-selectin) experienced a significant reduction, except sICAM-1. Among the pro-inflammatory cytokines, TNF-α was significantly reduced by 32.6% [(−42.2)–(−22.5)] (p < 0.0001), while the anti-inflammatory cytokine IL-10 increased by 674% (306–1299) (p < 0.0001). Among the angiogenic factors, only sEndoglin experienced a significant reduction. The CEC level trended to increase from 13 (3–33) cells/mL to 43 (8–140) cells/mL (p = 0.002). We did not observe any difference on the pre-session values of the molecules of interest between the first rheopheresis session and the last rheopheresis session. Conclusion: Rheopheresis immediately modified the inflammation balance and the endothelial injury biomarkers. Further studies are needed to understand the mechanisms underlying these biological observations.