The question of screening organ donors for hepatitis e virus: a case report of transmission by kidney transplantation in France and a review of the literature.

BACKGROUND: Hepatitis E is a potentially serious infection in organ recipients, with an estimated two-thirds of cases becoming chronic, and with a subsequent risk of cirrhosis and death. In Europe, transmission occurs most often through the consumption of raw or undercooked pork, more rarely through blood transfusion, but also after solid organ transplantation. Here we describe a case of Hepatitis E virus (HEV) infection transmitted following kidney transplantation and review the literature describing cases of HEV infection transmitted by solid organ transplantation. CASE PRESENTATION: Three weeks after kidney transplantation, the patient presented with an isolated minimal increase in GGT and hepatic cytolysis 6 months later, leading to the diagnosis of genotype 3c hepatitis E, with a plasma viral load of 6.5 log10IU/mL. In retrospect, HEV RNA was detected in the patient's serum from the onset of hepatitis, and in the donor's serum on the day of donation, with 100% identity between the viral sequences, confirming donor-derived HEV infection. Hepatitis E had a chronic course, was treated by ribavirin, and relapsed 10 months after the end of treatment. DISCUSSION: Seven cases of transmission of HEV by solid organ transplantation have been described since 2012 without systematic screening for donors, all diagnosed at the chronic infection stage; two patients died. HEV organ donor transmission may be underestimated and there is insufficient focus on immunocompromised patients in whom mild liver function test impairment is potentially related to hepatitis E. However, since HEV infection is potentially severe in these patients, and as evidence accumulates, we believe that systematic screening of organ donors should be implemented for deceased and living donors regardless of liver function abnormalities, as is already the case in the UK and Spain. In January 2024, the French regulatory agency of transplantation has implemented mandatory screening of organ donors for HEV RNA.

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges.

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.

Rheopheresis for severe peripheral arterial disease in hemodialysis patients: A clinical series.

BACKGROUND: Rheopheresis is a double-filtration plasmapheresis that removes high-molecular-weight molecules from the plasma and thereby lowers blood viscosity. This treatment has been proposed in hemodialysis (HD) patients for chronic limb-threatening ischemia (CLTI), but very few studies have evaluated the usefulness of this technique. PRINCIPAL OBJECTIVE: To assess 1-year amputation-free survival (AFS) of HD patients suffering from CLTI treated by rheopheresis. MATERIAL AND METHOD: We conducted a retrospective study of 28 consecutive HD patients treated by rheopheresis in three French dialysis centers between 1 February 2017 and 30 April 2019 in two indications resulting from CLTI, namely chronic ulceration or recent minor amputation with delayed healing. RESULTS: One-year AFS rate reached 53.6 (-19.8; +16.3)%. One-year overall survival rate reached 67.9 (-20.5; +13.1)%. Main causes of death were infections and related to palliative care implying reduction or withdrawal of regular dialysis treatment. Hypotension episodes were the main rheopheresis adverse events with a prevalence rate of 13.5%. Rheopheresis sessions significantly reduced fibrinogen, C-reactive protein, α2-macroglobulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, IgM, and estimated plasma viscosity (P < .0001). CONCLUSION: Rheopheresis may improve clinical outcomes of CLTI in HD patients. The assessment of rheopheresis effectiveness needs to be confirmed by a multicenter randomized controlled trial, such as the ongoing project in France (RHEO-PAD, NCT: 03975946).

Twenty years of the French Renal Epidemiology and Information Network.

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.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients.

Rheopheresis Performed in Hemodialysis Patients Targets Endothelium and Has an Acute Anti-Inflammatory Effect.

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.

Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients.

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.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients.