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.

Assisted PD throughout Europe: advantages, inequities, and solution proposals.

BACKGROUND: Peritoneal dialysis provides several benefits for patients and should be offered as first line kidney replacement therapy, particularly for fragile patients. Limitation to self-care drove assisted peritoneal dialysis to evolve from family-based care to institutional programs, with specialized care givers. Some European countries have mastered this, while others are still bound by the availability of a volunteer to become responsible for treatment. METHODS: A group of leading nephrologists from 13 European countries integrated real-life application of such therapy, highlighting barriers, lessons learned and practical solutions. The objective of this work is to share and summarize several different approaches, with their intrinsic difficulties and solutions, which might helpperitoneal dialysis units to develop and offer assisted peritoneal dialysis. RESULTS: Assisted peritoneal dialysis does not mean 4 continuous ambulatory peritoneal dialysis exchanges, 7 days/week, nor does it exclude cycler. Many different prescriptions might work for our patients. Tailoring PD prescription to residual kidney function, thereby maintaining small solute clearance, reduces dialysis burden and is associated with higher technique survival. Assisted peritoneal dialysis does not mean assistance will be needed permanently, it can be a transitional stage towards individual or caregiver autonomy. Private care agencies can be used to provide assistance; other options may involve implementing PD training programs for the staff of nursing homes or convalescence units. Social partners may be interested in participating in smaller initiatives or for limited time periods. CONCLUSION: Assisted peritoneal dialysis is a valid technique, which should be expanded. In countries without structural models of assisted peritoneal dialysis, active involvement by the nephrologist is needed in order for it to become a reality.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis.

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Prevalence of anti-neutrophil cytoplasmic antibody-associated vasculitis in the south of France, using the capture-recapture method.

OBJECTIVES: This study aimed to estimate the prevalence of ANCA-associated vasculitis (AAV), ie granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), in Southern France in 2018, and evaluate differences among Europeans and non-Europeans. METHODS: This population-based, cross-sectional study used four sources (hospitals, community-based physicians, laboratories, National Health Insurance) to identify adults ≥ 15 years diagnosed with GPA, MPA or EGPA, living in Hérault and Gard in 2018. Cases were defined using the ACR/EULAR classification criteria, and if necessary, the European Medicines Agency algorithm. Prevalence estimates were standardised to the world population and capture-recapture analysis was used to assess the comprehensiveness of the estimation. The influence of geographical origin was evaluated. RESULTS: 202 patients were selected, with 86 cases of GPA (42.6%), 85 cases of MPA (42.1%), and 31 cases of EGPA (15.3%). The standardised prevalence estimates per million inhabitants for 2018 were: 103 (95%CI 84 - 125) for AAV, 48 (95%CI 35 - 64) for GPA, 39 (95%CI 28 - 53) for MPA and 16 (95%CI 9 - 26) for EGPA, 36 (95%CI 25 - 50) for anti-PR3 positive AAV, 46 (95%CI 34 - 61) for anti-MPO positive AAV, and 16 (95%CI 9 - 26) for ANCA-negative AAV. The global estimation of comprehensiveness by capture-recapture analysis was 80.5%. The number of AAV cases was higher for non-European residents (P=0.001), particularly for MPA (P<0.0001). CONCLUSION: We provide a new estimate of AAV prevalence in France and show a higher prevalence of MPA in non-European patients.

Treatment trajectories of patients with End Stage Kidney Disease / Trajectoires des patients en suppléance

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of trajectory of ESKD patients, the following key messages were retained. Apart from a few rare, absolute or relative contraindications, till date, there is no medical consensus on the indications of one treatment modality as compared to another, and therefore, no recommendations allowing defining criteria for guiding patients, based on their characteristics, to a technique/treatment modality. In addition, the patients' choices and their changing needs over time must be taken into account. Thus, due to the limitations of each of these modalities, a good number of patients with stage 5 renal failure treated with kidney replacement therapy will move between these different modalities. For many years, the REIN registry has endeavoured to represent the patient flows between the different treatment modalities. In order to better understand and then optimise the trajectories followed by patients who have reached stage 5 of their chronic renal failure, it was necessary to develop tools to model these complex trajectories where the treatment modalities are considered as complementary.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question de la trajectoire des patients avec une maladie rénale stade 5, les messages clés suivants ont été retenus. En dehors de quelques rares contre-indications absolues ou relatives, à ce jour, il n'existe pas de consensus médical sur les indications d'une modalité de traitement par rapport à une autre, et par conséquent, de recommandations permettant de définir des critères d'orientation des patients en fonction de leurs caractéristiques vers une technique/modalité de traitement. Par ailleurs, les choix des patients et l'évolution de leurs besoins au cours du temps doivent être pris en compte. Ainsi, du fait des limites de chacune de ces modalités, un bon nombre de patients en insuffisance rénale stade 5 traités par suppléance rénale vont transiter entre ces différentes modalités. Depuis de nombreuses années, le registre REIN s'est attaché à représenter les flux de patients entre les différentes modalités de traitement. Afin de mieux connaître puis d'optimiser les trajectoires suivies par les patients arrivés au stade 5 de leur insuffisance rénale chronique, il a été nécessaire de mettre au point des outils permettant de modéliser ces trajectoires complexes où les modalités de traitement sont considérées comme complémentaires.

REIN: a tool to evaluate pratices / REIN : un outil au service de l'évaluation des pratiques

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its role in practices evaluation, the following key messages were retained. The evaluation of our practices allows improving them as proposed by the concept of the Edward Deming wheel (Plan, Do, Check, Act). Measurement also allows setting goals and targets. Where there are recommendations available, the REIN indicators allow comparison with the identified targets. The REIN registry is an interesting tool to observe the deployment and impact of the recommendations in dialysis units and to evaluate the professional practices taking into account the patients' characteristics and the changes in the recommendations. Finally, the treatment indicators analysed using REIN data show the great diversity of practices from one region to another, the result of habits, training of nephrologists, the history of the care offered and sometimes the geography of the region and its population.

À l'occasion des 20 ans du REIN (Réseau Épidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question de REIN comme outil pour l'évaluation des pratiques, les messages clés suivants ont été retenus. L'évaluation de nos pratiques permet de les améliorer comme proposé par le concept de la roue d'Edward Deming (Plan, Do, Check, Act). Se mesurer permet également de fixer des objectifs et des cibles. Lorsque des recommandations sont disponibles, les indicateurs REIN permettent de se comparer aux cibles identifiées. Le registre REIN est un outil intéressant pour observer le déploiement et l'impact des recommandations dans les unités de dialyse et évaluer les pratiques professionnelles en tenant compte des caractéristiques des patients et de l'évolution des recommandations. Enfin, les indicateurs de prise en charge analysés à l'aide des données REIN montrent la grande diversité des pratiques d'une région à l'autre, fruit des habitudes, de la formation des néphrologues, de l'historique de l'offre de soins et parfois de la géographie de la région et de sa population.

REIN: a tool to highlight inequalities in health / REIN : un outil au service de l'éclairage des inégalités en santé

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of Social Inequalities in Health, the following key messages were retained. Social inequalities in health exist throughout the journey of a patient with chronic kidney disease and manifest as territorial inequalities in access to home-based or independent dialysis treatment and to transplant, whether preemptive or otherwise. SIH are observed in adults as well as in the paediatric population. The female gender appears to be associated with a disparity in access to kidney transplant.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question des inégalités sociales de santé, les messages clés suivants ont été retenus. Les inégalités sociales de santé existent tout au long du parcours du patient atteint d'une maladie rénale chronique et se traduisent par des inégalités territoriales d'accès au traitement par dialyse au domicile ou autonome, à la greffe qu'elle soit préemptive ou non. Les ISS sont retrouvées chez l'adulte mais aussi dans la population pédiatrique. Le genre féminin semble associé à une disparité d'accès à la greffe rénale.

REIN: a tool at the service of the elderly patients / REIN : un outil au service des patients âgés

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of elderly CKD patients, the following key messages were retained. The population of elderly dialysis patients continues to grow. These patients have multiple comorbidities including pathologies specific to the elderly like undernutrition, walking and cognitive disorders. The data from the REIN registry has been the subject of numerous studies pertaining to this group showing heterogeneous prognosis and treatment, requiring to be better evaluated to target an individualised treatment. Decision support tools have been developed using the registry data to help nephrologists and patients in deciding whether to start replacement therapy and whether to refer elderly patients for assessment for a renal transplant. Finally, the risk-benefit evaluation of the different replacement therapies in this population should be monitored at the registry level and on a case-by-case basis in clinical practice.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question des patients âgées, les messages clés suivants ont été retenus. La population des patients âgés en dialyse ne cesse de croître. Ces patients ont de multiples comorbidités dont des pathologies spécifiques aux personnes âgées comme la dénutrition, les troubles de la marche et de la cognition. Les données du registre REIN ont fait l'objet de nombreuses études portant sur ce groupe montrant un pronostic et une prise en charge hétérogènes, nécessitant d'être mieux évalués pour cibler une prise en charge individualisée. Des outils d'aide à la décision ont été développés à l'aide des données du registre pour aider les néphrologues et les patients dans la décision de démarrer ou non un traitement de suppléance et d'orienter ou non les patients âgés vers un bilan d'évaluation en vue d'une transplantation rénale. Enfin, l'évaluation du bénéficerisque des différents traitements de suppléance dans cette population doit être poursuivie à l'échelle du registre et au cas par cas en pratique clinique.

Feasibility, Efficacy, and Safety of Peripheral Venous Access for Chronic Double-Filtration Plasmapheresis with Regional Citrate Anticoagulation.

INTRODUCTION: Peripheral venous access (PVA) is recommended as a first-line vascular approach for therapeutic plasmapheresis with centrifugation methods but not filtration, which usually requires high blood flow. We evaluated the feasibility, efficacy, and safety of double-filtration plasmapheresis (DFPP) with PVA, using ultrasound guidance and regional citrate anticoagulation (RCA), i.e., PVA-RCA-DFPP in patients undergoing chronic DFPP. Secondly, we assessed the number of central venous catheters (CVCs) avoided. METHODS: A single-center retrospective study evaluated 22 adult patients on chronic DFPP to perform PVA-RCA-DFPP. They were classified into 3 groups: successful (i.e., completion of sessions with PVA), primary failure (i.e., no sessions completed), secondary failure (i.e., ≥1 session with PVA completed but secondary return with CVC or arteriovenous fistula). RESULTS: Among the 22 patients included (64% men), 7 patients (32%) were classified as primary failures (2 patient refusals, 5 inadequate PVAs), 1 patient (5%) as a secondary failure (due to uncomfortable venipunctures), and 14 patients (64%) as successful. In the successful group including 12 patients treated for chronic inflammatory demyelinating polyneuropathy (CIDP) and 2 patients for familial hypercholesterolemia (FH) (2 patients), 116 sessions were performed, with a median treated plasma volume of 4.3 L [IQR 3.6-4.6] (45 mL/kg) for a median duration of 134 min [IQR 122-144], and a median blood flow of 94 mL/min [IQR 87-103]. For the CIDP group, 90% of sessions achieved a plasma volume >1 TPV, and for the FH group 91% of sessions achieved an LDLc reduction >60%. Eleven sessions out of 116 (9%) were interrupted, mostly due to PVA dysfunction (5/11) and circuit clotting (4/11). Session interruptions decreased significantly between each patient's first and following sessions (29% to 7%, p = 0.009). CONCLUSION: Chronic PVA-RCA-DFPP can be performed safely and efficiently, avoiding the use of CVCs.

Pregnancy in women on chronic dialysis in the last decade (2010-2020): a systematic review.

Background: Pregnant women with end-stage renal disease on chronic dialysis are at a high risk of maternal and foetal complications. Over the years, the prognosis of their pregnancies has improved with advances in dialysis treatments and maternal and neonatal care. We conducted this systematic review to examine the recent data on maternal and foetal outcomes in pregnant women with end-stage renal failure on chronic dialysis over the last decade. Methods: We made a systematic review of studies on pregnant women on chronic dialysis published between 1 January 2010 and 31 December 2020. We searched the following electronic databases: Medline via PubMed, Embase and the Cochrane Library, with search strategies for each database. We checked the titles and abstracts identified by the search equation, and two independent reviewers assessed the articles retrieved. For each study, the two reviewers separately recorded the data from each selected article on a standardized data extraction form. For each article, we recorded relevant general information on the study, patient demographic characteristics, dialysis schedule, pregnancy complications and outcomes, maternal complications, and foetal and neonatal outcomes. Results: The literature search yielded 1668 potentially relevant abstracts. After reviewing the titles, abstracts and full text, we identified 14 studies according to the inclusion criteria. All studies were observational, nine of them were retrospective and eight were from a single-centre experience. The total number of women included in these studies was 2364 (range 8-2008) and the total number of pregnancies was 2754 (range 8-2352). The patients' ages ranged from 15 to 45 years. Obesity was observed in 808 (34.2%) women and ranged from 1 to 778. Haemodialysis was the predominant modality with 2551 (92.6%) pregnancies, and 203 (7.4%) on peritoneal dialysis. Overall, 68 out of 402 (16.9%) spontaneous miscarriages, 21 out of 402 (5.2%) therapeutic abortions and 26 (8.3%) stillbirths among 313 (stillbirths and live births) were recorded. The mean or median gestational age at delivery ranged from 25.2 to 36 weeks. The main maternal complications were preeclampsia 11.9%, hypertension 7.7% and anaemia 3.9%. Live births represented 287 (71.4%) out of 402 pregnancies, birth weight ranged from 590 to 3500 g and preterm birth was the main, most common complication in all studies, ranging from 50% to 100%. Intrauterine growth restriction was present in 5.9% and small-for-gestational-age was reported in 18.9% of neonates. There were 22 (7.6%) neonatal deaths among 287 live births and 48 (15.3%) perinatal deaths among 313 total births (stillbirths and live births). Conclusions: Presumably, considering the increase in the number of publications and the total number of pregnancies reported therein, the frequency of pregnancy in patients with end-stage chronic kidney disease treated by chronic dialysis has increased. However, the practice of treating pregnant women on dialysis differs significantly among countries. These findings highlight the need to standardize the definition of outcomes and healthcare for pregnant women on dialysis.

Choosing the right chronic medication for hemodialysis patients. A short ABC for the dialysis nephrologist.

BACKGROUND: Adapting drug treatments for patients on hemodialysis with multiple chronic pathologies is a complex affair. When prescribing a medication, the risk-benefit analysis usually focuses primarily on the indication of the drug class prescribed. However, the pharmacokinetics of the chosen drug should also be taken into account. The purpose of our review was to identify the drugs to be favored in each therapeutic class, according to their safety and pharmacokinetic profiles, for the most common chronic diseases in patients on chronic hemodialysis. METHODS: We conducted a narrative review of the literature using Medline and Web of Science databases, targeting studies on the most commonly-prescribed drugs for non-communicable diseases in patients on chronic hemodialysis. RESULTS: The search identified 1224 articles, 95 of which were further analyzed. The main classes of drugs included concern the cardiovascular system (anti-hypertensives, anti-arrhythmics, anti-thrombotics, hypocholesterolemics), the endocrine and metabolic pathways (anti-diabetics, gastric anti-secretory, anticoagulant, thyroid hormones, anti-gout) and psychiatric and neurological disorders (antidepressants, anxiolytics, antipsychotics and anti-epileptics). CONCLUSION: We report on the most often prescribed drugs for chronic pathologies in patients on chronic hemodialysis. Most of them require adaptation, and in some cases one better alternative stands out among the drug class. More pharmacokinetic data are needed to define the pharmacokinetics in the various dialysis techniques.

Monitoring 25-OH and 1,25-OH vitamin D levels in hemodialysis patients after starting therapy: Does it make sense?

BACKGROUND AND AIMS: In hemodialysis patients, monitoring 25-hydroxyvitamin D (25(OH)D) levels is recommended. It is however unclear if monitoring 1,25-dihydroxyvitamin D (1,25(OH)2D) levels is interesting. MATERIALS AND METHODS: We repeatedly measured 1,25(OH)2D (DiaSorin Liaison analyser) and 25(OH)D (LCMS/MS) concentrations in patients newly treated by active or native vitamin D to study the impact of such treatments on serum concentrations. RESULTS: Ten patients were included in the native and 12 in the active vitamin D group. In the native group, a significant increase was observed between the baseline and the last 25(OH)D concentrations available (21.65[17.39;25.26] versus 33.49[28.60;40.30] ng/mL, p = 0.0059). The baseline and last available 1,25(OH)2D concentrations were not different (12.15[4.25;15.40] versus 11.35[9.72;21.85] pg/mL, p = 0.5566). In the active group, no difference was observed between the baseline and the last 25(OH)D concentrations (51.70[42.97;63.95] versus 50.89[42.02;64.49] ng/mL, p = 0.5186). The same observation was made for 1,25 (OH)2D concentrations (25.65[17.05;41.85] versus 28.70[23.36;43.73] pg/mL, p = 0.6221). Using a linear mixed model, a significant change over time was only observed in 25(OH)D serum levels for patients treated by with native vitamin D. CONCLUSION: Measuring 1,25(OH)2D levels in patients newly treated by active vitamin D does not seem useful in monitoring active vitamin D therapy.

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.

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.