Pregnancy Among Women Receiving Chronic Dialysis in France (2006-2020).

Introduction: In women receiving chronic dialysis, fertility is impaired. The objectives of this study were to estimate the incidence rate of pregnancies among women of childbearing age (15-50 years) receiving chronic dialysis from 2006 to 2020 in France, to describe the pregnancy outcomes and renal management during pregnancy. Methods: This national observational, retrospective study was based on data from the French REIN registry matched with the National Health Data System. Results: Over the period 2006 to 2020 in France, 348 pregnancies were identified in 240 women receiving chronic dialysis. The overall incidence of pregnancy was 11.1, 95% confidence interval (CI) (9.9-12.3) cases per 1000 person-years. Hemodialysis was the predominant modality during pregnancy. Main maternal complications were preeclampsia (n = 19) and gestational diabetes (n = 11). The most obstetric complications were premature rupture of membranes (n = 14) and polyhydramnios (n = 5). These pregnancies resulted in 174 (50%) abortions (<22 weeks), including 104 elective abortions (29.9%), 44 miscarriages (12.6%), 17 therapeutic abortions (4.9%), 5 ectopic pregnancies (1.4%), and 4 hydatidiform moles (1.2%). The remaining 174 (50%) pregnancies with deliveries (≥22 weeks) resulted in 166 live births (70 full-term [42.2%], 96 preterm births [57.8%]), and 8 stillbirths. Median gestational age was 36 weeks (32-38) for 174 deliveries. Conclusion: There have been improvements in maternal and fetal outcomes regarding pregnancy on chronic dialysis. However, our study shows a significant proportion of elective abortions. Better fertility management of women receiving chronic dialysis is advised by contraception or by pregnancy planning and early multidisciplinary follow-up.

A randomized crossover trial of regional anticoagulation modalities for intermittent hemodialysis.

INTRODUCTION: The optimal regional anticoagulation (RA) of dialysis filters in patients at risk of bleeding remains elusive. Inducing hypocalcemia within the filter by using a calcium-free dialysate has emerged as an easy-to-use heparin-free RA, including in critically ill patients, but comparative studies are lacking. METHODS: We conducted a multicentre, randomized, crossover trial to compare the efficacy and tolerance of two RAs (heparin-coated membrane (HCM) or calcium free dialysate with calcium reinjection according to ionic dialysance (CFD)) in patients requiring hemodialysis and at risk of bleeding. During the study period, each patient received two dialysis sessions (one with each RA in a randomly assigned order). The primary endpoint was the proportion of dialysis sessions completed (≥ 240 min). RESULTS: 94 patients were included in the intention-to-treat analysis, including 16 critically ill patients (17.0%). Coagulation and inflammation parameters, as well as hemodynamic status at baseline, were balanced between groups. Premature coagulation of the filter occurred in 19 HCM (20.9%) compared to 3 (3.2%) CFD sessions. In half of the sessions with premature termination, coagulation occurred before 180 minutes. The proportion of patients who completed the CFD session while failing to complete the HCM session (n = 17) was significantly higher than the proportion of patients who completed the HCM session while failing to complete the CFD session (n = 1; p < 0.001). Hemodynamic and metabolic tolerance were not different between groups. CONCLUSIONS: In individuals at risk of bleeding, RA with calcium-free dialysate significantly reduces the incidence of premature dialysis termination compared to heparin-coated membrane without safety concerns. Trial registration and statistical analysis plan: ClinicalTrials.gov identifier: NCT03842657.

Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicenter real-world study.

OBJECTIVES: Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in ANCA-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement. METHODS: In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form. RESULTS: Among the 31 patients (median age 72 years), 10 had a relapsing AAV, twenty had anti-myeloperoxidase antibodies, and thirty had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2), or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favorable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73m2 [23; 45] at month 12 (p< 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration). CONCLUSIONS: The GCs' sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.

Immunogenicity of SARS-CoV-2 vaccines in patients treated with chronic double filtration plasmapheresis.

BACKGROUND: The impact of chronic therapeutic plasmapheresis on humoral response following COVID-19 vaccination is poorly documented, especially among patients treated with double filtration plasmapheresis (DFPP). OBJECTIVES: This retrospective single-center study evaluated the humoral response after SARS-CoV-2 vaccination and studied anti-SPIKE seropositivity and antibody dynamics in patients with chronic DFPP at our institution. METHOD: All patients undergoing chronic DFPP at a tertiary center in France from December 2020 to November 2022 were included. We defined one patient subgroup as Group 1 to evaluate anti-SPIKE seropositivity after vaccination, with three groups based on their anti-SPIKE titers: (Group 1A) nonresponders (<0.8 UI/mL), (Group 1B) weak responders (0.8 to <250 binding antibody unit [BAU]/mL), and (Group 1C) strong responders (>250 BAU/mL). Group 2 served to evaluate antibody dynamics with anti-SPIKE levels measured 3 months after initial vaccination, Group 2A having a sustained level and Group 2B a declining pattern. RESULTS: The 21 patients included had a median age of 63 years, and 13 (56%) were male. The indications for chronic DFPP mainly included dysimmune pathologies (15; 71%) and familial dyslipidemia (6; 29%). For the humoral response to vaccination in Patient Group 1, the only nonresponder was a patient who had undergone kidney transplantation 30 months earlier and was on immunosuppressive medication. For Patient Group 2, the median follow-up of antibody titers was 13 months [12-13]. Two distinct patterns of anti-SPIKE dynamics were observed: a rapid decline in anti-SPIKE antibody titers within 6 months following the initial vaccination or booster dose (n = 10 [71.4%] Group 2A) and stable anti-SPIKE levels above 250 BAU/mL over >6 months (n = 4 [28.6%] Group 2B) with more patients with familial dyslipidemia in the former. CONCLUSIONS: Humoral response to SARS-CoV-2 vaccination appears robust in patients undergoing chronic DFPP and may be linked to patients' immune status rather than DFPTP itself. Our results support current recommendations for administering three doses of vaccine with a booster every 6 months.

Interest of therapeutic plasmapheresis in a chronic hemodialysis patient with severe bullous pemphigoid.

Bullous pemphigoid is the most common autoimmune blistering disease induced by autoantibodies against basement membrane anchoring proteins (anti-BP-180 and anti-BP-230). The disease generally appears after the age of 70 and is associated with a 23.5% 1-year mortality, especially in diabetics, or in the presence of ischemic heart disease and high anti-BP-180. Treatment starts with topical steroids but some patients may require oral steroids and systemic immunosuppression. We, hereby, discuss a diabetic patient on chronic hemodialysis, with severely relapsed bullous pemphigoid under biotherapy with omalizumab, who was successfully treated with five sessions of double filtration plasmapheresis, thus avoiding the need for systemic steroids.

Prevalence of chronic kidney disease in France: methodological considerations and pitfalls with the use of Health claims databases.

Background: Health policy-making require careful assessment of chronic kidney disease (CKD) epidemiology to develop efficient and cost-effective care strategies. The aim of the present study was to use the RENALGO-EXPERT algorithm to estimate the global prevalence of CKD in France. Methods: An expert group developed the RENALGO-EXPERT algorithm based on healthcare consumption. This algorithm has been applied to the French National Health claims database (SNDS), where no biological test findings are available to estimate a national CKD prevalence for the years 2018-2021. The CONSTANCES cohort (+219 000 adults aged 18-69 with one CKD-EPI eGFR) was used to discuss the limit of using health claims data. Results: Between 2018 and 2021, the estimated prevalence in the SNDS increased from 8.1% to 10.5%. The RENALGO-EXPERT algorithm identified 4.5% of the volunteers in the CONSTANCES as CKD. The RENALGO-EXPERT algorithm had a positive predictive value of 6.2% and negative predictive value of 99.1% to detect an eGFR<60 ml/min/1.73 m². Half of 252 false positive cases (ALGO+, eGFR > 90) had been diagnosed with kidney disease during hospitalization, and the other half based on healthcare consumption suggestive of a 'high-risk' profile; 95% of the 1661 false negatives (ALGO-, eGFR < 60) had an eGFR between 45 and 60 ml/min, half had medication and two-thirds had biological exams possibly linked to CKD. Half of them had a hospital stay during the period but none had a diagnosis of kidney disease. Conclusions: Our result is in accordance with other estimations of CKD prevalence in the general population. Analysis of diverging cases (FP and FN) suggests using health claims data have inherent limitations. Such an algorithm can identify patients whose care pathway is close to the usual and specific CKD pathways. It does not identify patients who have not been diagnosed or whose care is inappropriate or at early stage with stable GFR.

Anti-GBM antibody in a patient with diabetic nephropathy; all that glitters is not gold.

We present the case of a 58-year-old male diabetic patient admitted to our department for a slight decrease in kidney function, with nephrotic range proteinuria, hematuria (16,000/ml) and positive anti-glomerular basement membrane antibodies. Kidney biopsy revealed diabetic nephropathy with no evidence of crescent formation or linear immunoglobulin deposits along the basement membrane. We discuss the various clinical settings involving positive anti-glomerular basement membrane in the absence of crescentic glomerulonephritis.

Successful pregnancy after 10 consecutive failures in a liver transplant patient with advanced kidney failure.

We report a successful, albeit complicated pregnancy with a live-born healthy baby at 28 weeks' gestation, after 10 pregnancy failures, in a 39-year-old patient with a history of liver transplantation and chronic kidney disease with hypertension and proteinuria. Multidisciplinary management (obstetrician, nephrologist and hepatology transplant specialist) allowed close monitoring, adaptation of immunosuppressive treatments and strict control of fetal growth. The onset of preeclampsia at 28 weeks' gestation led to a cesarean section, resulting in the birth of a healthy 830 g boy, with subsequent normal development. Following pregnancy, the patient experienced liver transplant rejection, which resolved after adapting immunosuppressive drugs. No deterioration in kidney function was observed in the year following delivery.

Hot Spot of Complement Factor I Rare Variant p.Ile357Met in Patients With Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease due to a dysregulation of the complement alternative pathway. Complement factor I (CFI) negatively regulates the alternative pathway and CFI gene rare variants have been associated to aHUS with a low disease penetrance. We report 10 unrelated cases of HUS associated to a rare CFI variant, p.Ile357Met (c.1071T>G). All patients with isolated p.Ile357Met CFI missense variant were retrospectively identified among patients included between January 2007 and January 2022 in the French HUS Registry. We identified 10 unrelated patients (70% women; median age at HUS diagnosis, 36.5 years) who carry the same rare variant p.Ile357Met in the CFI gene. Seven patients (cases 1-7) presented with aHUS in the native kidney associated with malignant hypertension in 5 patients. None received a C5 inhibitor. Two of these cases occurred in the peripartum period with complete recovery of kidney function, while 5 of these patients reached kidney failure requiring replacement therapy (KFRT). Four patients with KFRT subsequently underwent kidney transplantation. Three later developed C3 glomerulopathy in their kidney graft, but none had aHUS recurrence. Three other patients (cases 8-10) experienced de novo thrombotic microangiopathy after kidney transplantation, precipitated by various triggers. The rare CFI variant p.Ile357Met appears to be a facilitating genetic factor for HUS and for some forms of secondary HUS.

General practitioners' representation of early-stage CKD is a barrier to adequate management and patient empowerment: a phenomenological study.

BACKGROUND: In high-income countries, chronic kidney disease (CKD) affects over 10% of the population. Identifying these patients early is a priority, especially as new treatments are available to reduce the risk of cardiovascular and renal morbidity. We aimed at understanding the management and care pathway of patients with early-to-moderate CKD defined as an estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 (CKD-EPI), by analyzing the experience of general practitioners in a region in France. METHODS: This qualitative semiopragmatic phenomenological study analyzed in-depth interviews held with a purposive sample (age, gender, training, type of practice, rural/urban context) of 24 general practitioners, with triangulation of research until data saturation. RESULTS: From diagnostic, etiological and prognostic viewpoints, the general practitioners enrolled in our study perceived CKD as a complex, poorly-defined clinical entity in asymptomatic and multimorbid patients. They distinguished it from a rare condition they considered as 'mainly renal'. The fact that they did not perceive early-stage CKD as a disease was a hindrance to patient care, which should protect the kidneys with a preventive approach. Indeed, general practitioners perceived CKD patient management as a pathway requiring a personalized, integrative model, common to all chronic diseases, without necessarily involving a nephrologist, at least in the early stages. CONCLUSIONS: This study shows how the general practitioners' representations influence their attitudes and interventions. Clarifying the concept of early-stage CKD by taking factors like age and etiology into account would facilitate personalized management of this heterogeneous, often multimorbid, population. Finally, organizational models to support patient empowerment in an integrative care pathway must be established and validated.

Adverse Events and Infectious Complications in the Critically Ill Treated by Plasma Exchange: A Five-Year Multicenter Cohort Study.

OBJECTIVES: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors. DESIGN: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not. SETTING: Four ICUs of French university hospitals. PATIENTS: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies (n = 32, 26%), myasthenia gravis (n = 25, 20%), and acute polyradiculoneuropathy (n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001). CONCLUSIONS: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection.