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Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.
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The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.
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Introduction: During COVID-19, renal impairment is associated with poor prognosis in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Methods: In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation (MV) for ARDS were enrolled in 3 ICUs. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis (UPE) and quantification, was performed within 24 hours after MV onset. Results: From March 2020 to December 2021, 135 patients were enrolled as follows: 100 with COVID-19 ARDS and 35 with non-COVID-19 ARDS. UPE found more tubular dysfunction in patients with COVID-19 (68% vs. 21.4%, P < 0.0001) and more normal profiles in patients without COVID-19 (65.0% vs. 11.2%, P = 0.0003). Patients with COVID-19 significantly displayed early urinary leakage of tubular proteins such as beta-2-microglobulin (ß2m) and free light chains, tended to display acute kidney injury (AKI) more frequently (51.0% vs. 34.3%, P = 0.088), had longer MV (20 vs. 9 days, P < 0.0001) and longer ICU stay (26 vs. 15 days, P < 0.0001). In COVID-19 ARDS, leakage of free lambda light chain was associated with the onset of Kidney Disease: Improving Global Outcomes (KDIGO) ≥2 AKI (odds ratio [OR]: 1.014, 95% confidence interval [CI] 1.003-1.025, P = 0.011). Conclusion: Patients with COVID-19-related ARDS display a proximal tubular dysfunction before the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable noninvasive tool to assess proximal tubular dysfunction in the ICU.
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Simulation is a technique to replace and amplify real experiences with guided ones that evoke or replicate substantial aspects of the real world in a fully interactive fashion. In nephrology (a particularly complex specialty), simulation can be used by patients, nurses, residents, and attending physicians alike. It allows one to learn techniques outside the stressful environment of care such as central venous catheter placement, arteriovenous fistula management, learning about peritoneal dialysis, or performing a kidney biopsy. Serious games and virtual reality are emerging methods that show promise. Simulation could also be important in relational aspects of working in a team or with the patient. The development of simulation as a teaching tool in nephrology allows for maintaining high-quality training for residents, tailored to their future practice, and minimizing risks for patients. Additionally, this education helps nephrologists maintain mastery of technical procedures, making the specialty attractive to younger generations. Unfortunately, the inclusion of simulation training programmes faces occasional logistical or funding limitations that universities must overcome with the assistance and innovation of teaching nephrologists. The impact of simulation-based teaching on clinical outcomes needs to be investigated in clinical studies.
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Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI.
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Disfunção Cognitiva , Modelos Animais de Doenças , Insuficiência Renal Crônica , Animais , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/psicologia , Insuficiência Renal Crônica/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Humanos , Camundongos , Peixe-Zebra , Cognição , Ratos , Rim/fisiopatologia , Rim/metabolismoRESUMO
Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.
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Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Adulto , Humanos , Rim/patologia , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/terapia , Microangiopatias Trombóticas/patologia , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Proteínas do Sistema Complemento , Testes de Função RenalRESUMO
INTRODUCTION: Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria, and its defining histopathological set of features is in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology, with a significant number of re-established diagnoses. The aim of this study was to investigate the diagnostic yield of ES in patients with a clinical diagnosis of hypertensive nephropathy. METHOD: Since September 2018, ES has been readily available as part of the routine diagnostic work-up in our institution. The indication of ES includes hypertensive nephropathy of early onset (i.e., <45 years old). We retrospectively collected the ES data performed in the context of hypertensive nephropathy in our institution between September 2018 and February 2021. RESULTS: A total of 128 patients were sequenced in the context of hypertensive nephropathy with early onset. The chief indications of ES were an early onset of CKD (47%), family history of kidney disease (8%), or both (18%). We detected diagnostic variants in 19 of the 128 patients (15%), encompassing a total of 13 different monogenic disorders. The diagnostic yield of ES was lower in patients of African ancestry (diagnostic yield of 7 vs. 30% in non-African ancestry patients, p < 0.001). CONCLUSIONS: The high diagnostic yield of ES (15%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria, including histological criteria, supposed to characterize the condition. This was especially true in patients with no African ancestry, where ES positivity reached 30%.
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Sequenciamento do Exoma , Hipertensão Renal , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Hipertensão Renal/genética , Hipertensão Renal/diagnóstico , Idade de Início , Nefrite/genética , Nefrite/diagnóstico , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/diagnóstico , Nefroesclerose/genética , Nefroesclerose/diagnósticoRESUMO
INTRODUCTION: Patients with chronic kidney disease (CKD) have an increased risk of stroke, and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and acute kidney injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy. METHODS: This multicenter cohort study included patients in the acute phase of ischemic stroke due to large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS). RESULTS: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3-6: 50.0% vs. 41.7%, p = 0.262) but higher mortality (24.2% versus 9.5%, p = 0.004). In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas score: 1.7 ± 0.8 vs. 1.0 ± 0.8, p = 0.002), lower initial infarct volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p = 0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3-6: 63.8% vs. 49.0%, p = 0.002) and mortality (23.4% versus 7.7%, p = 0.002). In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3-6: adjOR 2.79 [1.11-7.02], p = 0.029) and mortality (adjOR 2.52 [1.03-6.18], p = 0.043) at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome. CONCLUSIONS: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis.
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Injúria Renal Aguda , AVC Isquêmico , Insuficiência Renal Crônica , Trombectomia , Humanos , Masculino , Feminino , Trombectomia/efeitos adversos , Idoso , AVC Isquêmico/cirurgia , AVC Isquêmico/etiologia , AVC Isquêmico/complicações , AVC Isquêmico/mortalidade , Insuficiência Renal Crônica/complicações , Pessoa de Meia-Idade , Prognóstico , Injúria Renal Aguda/etiologia , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos de Coortes , Fatores de RiscoRESUMO
This article aims to summarize the "Quoi de neuf en néphrologie?" session held at the 2023 SFNDT Congress in Liège and sessions focused on updates regarding IgA nephropathy (NIgA) and ANCA-associated vasculitis. The agenda for the nephrology "Quoi de neuf en néphrologie?" session this year was to review key publications from non-nephrology journals, discussing topics such as nephroprotection, treatment of glomerulopathies (IgA and APOL1), clinical trials on arterial hypertension, urinary lithiasis, and other areas of renal physiology, including glomerular filtration rate estimation.
Cet article a pour but de résumer d'une part la session « Quoi de neuf en néphrologie ? ¼ qui a eu lieu au congrès de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) 2023 à Liège en Belgique, mais également les sessions portant sur les actualités de la néphropathie à IgA (NIgA) et des vascularites associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA). Le cahier des charges du « Quoi de neuf en néphrologie ? ¼ cette année était de reprendre les principaux articles publiés dans des revues hors néphrologie et s'est articulé sur les publications autour de la néphroprotection, du traitement des glomérulopathies (IgA et APOL1), des essais cliniques sur l'hypertension artérielle ou dans la lithiase urinaire, ou dans d'autres champs de la physiologie rénale comme l'estimation du débit de filtration glomérulaire.
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Glomerulonefrite por IGA , Nefrologia , Urolitíase , Humanos , Glomerulonefrite por IGA/terapia , Taxa de Filtração Glomerular , Apolipoproteína L1RESUMO
Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.
La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.
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Nefropatias , Nefrologia , Humanos , Nefropatias/diagnóstico , Nefropatias/terapia , Nefropatias/patologia , França , Rim/patologia , BiópsiaRESUMO
RATIONALE & OBJECTIVE: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018. EXPOSURES: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels. OUTCOMES: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events. ANALYTICAL APPROACH: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively. RESULTS: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospitalization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplantation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P=0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P=0.02). LIMITATIONS: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored. CONCLUSIONS: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease. PLAIN-LANGUAGE SUMMARY: AA amyloidosis is a severe and rare disease. Kidney involvement is frequent and leads to end-stage kidney disease. Because of the involvement of other organs, these patients are often frail, which has raised concerns about their suitability for kidney transplantation. We reviewed all patients with AA amyloidosis nephropathy who underwent kidney transplantation in France in the recent era (2008-2018) and found that the outcomes after kidney transplantation were favorable, with 85.5% of patients still alive 5 years after transplantation, a survival rate that is comparable to the outcomes of patients receiving a transplant for other forms of kidney diseases. Recurrence of amyloidosis in the transplanted kidney was infrequent (5.8%). These data support the practice of kidney transplantation for patients with AA amyloidosis who experience kidney failure.
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Amiloidose , Nefropatias , Falência Renal Crônica , Transplante de Rim , Humanos , Pessoa de Meia-Idade , Transplante de Rim/métodos , Estudos de Coortes , Proteína C-Reativa , Estudos Retrospectivos , Amiloidose/cirurgia , Amiloidose/complicações , Falência Renal Crônica/cirurgia , Falência Renal Crônica/complicações , Nefropatias/etiologia , Estudos Multicêntricos como Assunto , Proteína Amiloide A SéricaRESUMO
People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood-brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.
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Patients with chronic kidney disease (CKD) have an increased risk of cognitive disorders, presenting as vascular dementia, compared with the general population. These cognitive disorders occur early during the course of the kidney disease and evolve in parallel with the decline in glomerular filtration rate. They affect 30 to 80 % of patients with stage 5 CKD. Kidney transplantation only partially improves cognitive impairment. In this narrative review, we summarize the epidemiology and recent clinical and experimental data on cognitive impairment in CKD and discuss the potential specific mechanisms. Among the factors associated with cognitive impairment, the accumulation of uremic toxins such as indoxyl sulfate appears to be a specific risk factor for cognitive decline. These toxins have an endothelial toxicity that can disrupt the cerebral endothelium. The rupture of the blood-brain barrier (BBB) is a mechanism implicated in several neurodegenerative pathologies and systemic diseases with cerebral tropism. Recent experimental findings in CKD indicate that disruption of the BBB appears to be an important mechanism behind cognitive impairment in CKD. In murine models of CKD, increased BBB permeability is linked to memory impairment and aryl hydrocarbon receptor activation following accumulation of circulating indoxyl sulfate. This disruption of the BBB could also have harmful consequences for stroke susceptibility and drug neurotoxicity in CKD patients.
Les patients atteints de maladie rénale chronique (MRC) présentent un risque accru de troubles neurocognitifs par rapport à la population générale, se présentant sous la forme d'une démence vasculaire. Ces troubles cognitifs interviennent précocement dans la maladie rénale et évoluent en parallèle au déclin du débit de filtration glomérulaire. Ils concernent 30 à 80 % des patients au stade 5 de la MRC. La transplantation rénale n'améliore que partiellement les troubles cognitifs. Dans cette revue narrative, nous résumons l'épidémiologie et les données cliniques et expérimentales récentes sur les troubles cognitifs dans la MRC, et nous en abordons les mécanismes spécifiques potentiels. Parmi les facteurs associés aux atteintes cognitives, l'accumulation des toxines urémiques, comme l'indoxyl sulfate, apparaît comme un facteur de risque spécifique de déclin cognitif. Ces toxines possèdent une toxicité endothéliale pouvant perturber l'endothélium cérébral. La rupture de la barrière hémato-encéphalique (BHE) est un mécanisme impliqué dans plusieurs pathologies neuro-dégénératives et des maladies systémiques à tropisme cérébral. Les résultats de travaux expérimentaux récents dans la MRC indiquent que la rupture de la BHE semble être un mécanisme important des troubles cognitifs au cours de la MRC. Dans les modèles murins de MRC, la perméabilité accrue de la BHE est liée à l'atteinte de la mémoire et à l'activation d'Aryl hydrocarbon Receptor suite à l'accumulation d'indoxyl sufate circulant. Cette rupture de la BHE pourrait également avoir des conséquences néfastes sur la susceptibilité aux accidents vasculaires cérébraux (AVC) et à la neurotoxicité médicamenteuse chez les patients MRC.
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Disfunção Cognitiva , Insuficiência Renal Crônica , Toxinas Biológicas , Uremia , Humanos , Camundongos , Animais , Barreira Hematoencefálica , Toxinas Urêmicas , Indicã , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Disfunção Cognitiva/etiologia , Uremia/complicaçõesRESUMO
Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.
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Lupus nephritis (LN) is one of the main determinants of the severity of systemic lupus erythematosus (SLE). LN flares can lead to organ damage with chronic kidney disease (CKD) or even end-stage kidney disease (ESKD) and impair patients' survival. The "treat-to-target" strategy, which aims at obtaining and maintaining remission or low disease activity of SLE to alleviate symptoms and prevent organ damage, also refers to the control of residual activity in the kidney. But damage in SLE can also come from treatments, and toxicities related to long-term use of treatments should be prevented. This may contribute to the frequent nonadherence in patients with SLE. The de-escalation or even weaning of treatments whenever possible, or "think-to-untreat" (T2U) strategy, is to be considered in patients with LN. This possibility of treatment weaning in LN was explored in retrospective cohorts, on the basis of long-term clinical remission. It was also proposed prospectively with a kidney-biopsy-based approach, combining clinical and pathologic remission to secure treatment weaning. The WIN-Lupus trial was the first randomized controlled trial comparing the continuation to the discontinuation of maintenance immunosuppressive therapy (IST) after 2 to 3 years in patients with LN in remission. It showed a higher risk of severe SLE flares in patients who discontinued treatment, but also a possibility of weaning without flare in some patients, who need to be better identified. We propose here a narrative review of the available literature on the weaning of treatment in LN and discuss how to secure a T2U strategy.
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Patients with chronic kidney disease (CKD) have an increased risk of both ischaemic and haemorrhagic stroke compared with the general population. Both acute and chronic kidney impairment are independently associated with poor outcome after the onset of a stroke, after adjustment for confounders. End-stage kidney disease (ESKD) is associated with a 7- and 9-fold increased incidence of both ischaemic and haemorrhagic strokes, respectively, poorer neurological outcome and a 3-fold higher mortality. Acute kidney injury (AKI) occurs in 12% of patients with stroke and is associated with a 4-fold increased mortality and unfavourable functional outcome. CKD patients seem to have less access to revascularisation techniques like thrombolysis and thrombectomy despite their poorer prognosis. Even if CKD patients could benefit from these specific treatments in acute ischaemic stroke, their prognosis remains poor. After thrombolysis, CKD is associated with a 40% increased risk of intracerebral haemorrhage (ICH), a 20% increase in mortality and poorer functional neurological outcomes. After thrombectomy, CKD is not associated with ICH but is still associated with increased mortality, and AKI with unfavourable outcome and mortality. The beneficial impact of gliflozins on the prevention of stroke is still uncertain. Non-traditional risk factors of stroke, like uraemic toxins, can lead to chronic cerebrovascular disease predisposing to stroke in CKD, notably through an increase in the blood-brain barrier permeability and impaired coagulation and thrombosis mechanisms. Preclinical and clinical studies are needed to specifically assess the impact of these non-traditional risk factors on stroke incidence and outcomes, aiming to optimize and identify potential therapeutic targets.
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Injúria Renal Aguda , Isquemia Encefálica , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Estudos Retrospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , IsquemiaRESUMO
BACKGROUND: Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. METHODS: To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. RESULTS: A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. CONCLUSIONS: This suggests that kidney biopsy might be beneficial in young patients with MH.
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Hipertensão Maligna , Hipertensão , Nefroesclerose , Humanos , Nefroesclerose/complicações , Hipertensão Maligna/complicações , Hipertensão Maligna/epidemiologia , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Rim , Hipertensão Essencial , Biópsia , Hipertensão/complicações , Hipertensão/patologiaRESUMO
BACKGROUND: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. METHODS: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). RESULTS: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). CONCLUSIONS: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www. CLINICALTRIALS: gov ( NCT03918603 ). Registered 17 April 2019.