A growing body of evidence supports the existence of a kidney-brain axis that may contribute to the cognitive decline observed in chronic kidney disease (CKD). Current demographic trends suggest that incidence and prevalence of both conditions will continue to rise. In this narrative review, we aim to explore the epidemiological data supporting the association between CKD and neurocognitive health; the potential existence of a CKD-specific cognitive pattern; the underlying pathophysiological mechanisms; and the diagnostic and therapeutic implications, both pharmacological and non-pharmacological. Epidemiological studies consistently indicate an association between CKD and cognitive impairment. Executive functions are frequently affected, although no distinct CKD-related cognitive phenotype has yet been clearly defined. The pathophysiology extends beyond vascular contribution and involves multiple interdependent mechanisms, with a key role attributed to the accumulation of uremic toxins in CKD. Accurate diagnosis of both CKD and cognitive impairment requires careful selection and application of appropriate tests and biomarkers. Therapeutic strategies include both pharmacological and non-pharmacological interventions. The complexity of the kidney-brain axis highlights the need for expanded research efforts and multidisciplinary collaboration among patients, healthcare providers, nephrologists, neurologists, geriatricians, radiologists, and basic scientists.

La maladie rénale chronique (MRC) constitue un problème majeur de santé publique, touchant près de 10 % de la population adulte, avec une part importante de diagnostics réalisés à un stade avancé, nécessitant souvent une suppléance rénale. Face à une morbidité et une mortalité élevée, notamment liées aux complications cardiovasculaires et métaboliques, l’enjeu est d’optimiser la prévention et la prise en charge à chaque étape de la maladie. La MRC implique des patients particulièrement complexes en raison de multiples comorbidités et d’une polypharmacie fréquente, plaçant le pharmacien au cœur de la collaboration entre médecins généralistes et néphrologues dans la prise en charge des patients.Cette revue narrative explore cette collaboration sous trois angles : d’abord, en ville, où le médecin généraliste détecte précocement les signes de MRC et oriente vers le néphrologue, tandis que le pharmacien d’officine sécurise les traitements et conseille les patients au quotidien. Outre sa participation à la diffusion des connaissances sur la MRC, le pharmacien pourrait aussi jouer un rôle actif dans les campagnes de dépistage de la maladie, en lien étroit avec le biologiste médical qui produit et interprète les données biologiques nécessaires au diagnostic et au suivi. Ensuite, en structure de dialyse, où le néphrologue assure la prise en charge globale du patient et travaille en synergie avec le pharmacien du centre, garant de la qualité de l’eau, de la gestion des dispositifs médicaux et de la sécurité des traitements dans un environnement technique complexe. Enfin, la revue souligne l’apport de la pharmacoépidémiologie, discipline où néphrologues et pharmacologues unissent leurs compétences pour analyser l’usage et la sécurité des traitements dans une population souvent exclue des essais cliniques, afin d’adapter les prescriptions à la réalité. Cette coopération pluridisciplinaire apparaît essentielle pour assurer un parcours de soins fluide et sécurisé chez les patients atteints de MRC.

Osteoporosis and chronic kidney disease (CKD)–metabolic bone disease (MBD) (CKD-MBD) are increasingly recognized as overlapping conditions, particularly in the aging population. Declining renal function and skeletal fragility often coexist, because CKD-MBD may develop in a skeleton already compromised by preexisting osteoporosis. Adynamic bone, often resulting from excessive suppression of parathyroid hormone (PTH) and now a common form of renal osteodystrophy (ROD), may histologically resemble low-turnover osteoporosis; distinguishing between the 2 under light microscopy remains difficult, and reliable differentiation often depends on clinical context. Nevertheless, nephrologists and nonnephrologist bone specialists frequently work in parallel rather than in collaboration.This separation has contributed to persistent diagnostic gaps and fragmented management, especially in patients with advanced CKD. Advances in imaging, biochemical markers, and bone histomorphometry have improved insight into disease mechanisms; however, limitations in current diagnostic approaches remain. Osteoporosis therapies are frequently underused in CKD, despite growing evidence supporting efficacy and safety across a broader range of kidney function than previously assumed. Despite efforts to refine the definition of osteoporosis beyond bone mineral density (BMD) alone, clinical misclassification continues.Beyond skeletal health, vascular calcification (VC)—driven by disordered calcium–phosphate homeostasis—remains insufficiently prioritized in clinical decision-making, despite its strong association with cardiovascular morbidity and mortality in CKD. Emerging concepts, such as intermittent PTH administration, an established treatment in osteoporosis, illustrate the potential for interventions that may restore mineral balance and improve skeletal integrity in selected CKD populations. Whether such strategies can also favorably influence cardiovascular risk remains uncertain and warrant investigation. This integrated framework may improve interdisciplinary care.

Background Dialysate composition is crucial for managing secondary hyperparathyroidism (SHPT) in patients on hemodialysis. Acetate-based dialysates elevate serum acetate and trigger adverse effects, while citrate and hydrochloric acid formulations might offer distinct clinical benefits. Methods In this longitudinal observational real-life study, 876 adult patients on hemodialysis were classified by acid component of the dialysate (acetic acid, citric acid, or hydrochloric acid). Monthly pre-dialysis parathyroid hormone (PTH) and bone-mineral biomarkers were measured. A linear mixed model (LMM), adjusted for baseline PTH, demographics, and clinical covariates, evaluated PTH trajectories over two years. The significance of the main effect of dialysate and its interaction with time was assessed using likelihood-ratio tests (LRT). Results At baseline, serum PTH was significantly higher in the acetate group. The LMM confirmed significant influence of dialysate type (p < 0.001) and its interaction with time (p = 0.048) on PTH trajectories. Over two years, acetate showed a modest, non-significant PTH reduction of 2.9% (95% CI: -8.8% to +3.4%), whereas hydrochloric acid resulted in a significant cumulative PTH reduction of 10.9% (95% CI: -15.7% to -0.2%), with a significantly different yearly slope versus acetate (p = 0.044). Citrate showed a modest, non-significant change compared to acetate (-2.3%; 95% CI: -6.7% to +8.4%). Baseline PTH, phosphate, prior hypercalcemia, and dialysate calcium concentration were major predictors in the model. Conclusions In adjusted longitudinal analyses, hydrochloric acid-based bicarbonate dialysate was associated with a steeper decline in pre-dialysis PTH over two years compared with acetate, while citrate did not differ from acetate. Prospective studies are needed to confirm whether buffer composition influences PTH control under standardized calcium-bath strategies.

Chronic kidney disease (CKD) is a major public health issue, affecting nearly 10% of the adult population, with a significant proportion of diagnoses occurring at advanced stages, often requiring renal replacement therapy. Given the high morbidity and mortality associated with CKD, particularly due to cardiovascular and metabolic complications, there is a critical need to optimize prevention and management at every stage of the disease. CKD patients are particularly complex, owing to multiple comorbidities and frequent polypharmacy, positioning the pharmacist at the center of collaboration between general practitioners and nephrologists. This narrative review explores this collaboration from three perspectives: first, in primary care, where general practitioners play a key role in the early detection of CKD and referral to nephrologists, while community pharmacists play a key role in medication safety, optimization, and patient education. The pharmacist, beyond his participation in the dissemination of knowledge about CKD, could also participate in CKD screening campaigns, in close coordination with medical biologists responsible for generating and interpreting the laboratory data required for diagnosis and follow-up. Second, within dialysis centers, nephrologists oversee the comprehensive management of patients and work in synergy with hospital pharmacists, who are responsible for water quality, management of dialysis-related medical devices, and medication safety in a technically complex environment. Finally, the review highlights the contribution of pharmacoepidemiology, a field where nephrologists and pharmacologists combine their expertise to analyze drug utilization and safety in a population often excluded from clinical trials, with the goal of tailoring prescriptions to real-world practice. This multidisciplinary cooperation appears essential to ensure a safe continuum of care for patients with CKD.

BACKGROUND AND HYPOTHESIS:The standard approach to anaemia in non-dialysis chronic kidney disease (CKD) does not account for potential age- or sex-specific related risks. We assessed differences in the association between haemoglobin and major cardiovascular events (MACE+) in men and women with CKD, by age groups. METHODS:Using 5-year longitudinal data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort, we studied patients with CKD stage 2-5 not treated with erythropoiesis-stimulating agents (ESA). The main outcome was MACE+, defined as cardiovascular death, myocardial infarction, stroke or hospitalization for acute heart failure. Competing events were initiation of kidney replacement therapy and non-cardiovascular death. In each of the four predefined subgroups by sex and age (≤70 versus >70 years at baseline), we estimated hazard ratios (HR) of current values of haemoglobin using a cause-specific Cox model adjusted for current values of glomerular filtration rate and transferrin saturation. All current values of biomarkers were first estimated in a multivariate-shared random effect joint model. RESULTS:Analyses considered 29 042 haemoglobin measurements from 2791 patients, and 364 MACE+. The association between current haemoglobin and log hazard of MACE+ was linear in men and J-shaped in women. For a haemoglobin of 10.5 g/dL, as compared with 11.5 g/dL, the hazard of MACE+ at any time was increased by 60% in younger women [HR = 1.6, 95% confidence interval (CI) 1.1-2.4], 70% in older women (HR = 1.7, 95% CI 1.3-2.4), 30% in younger men (HR = 1.3 95% CI 1.1-1.5) and 20% in older men (HR = 1.2 95% CI 1.1-1.4). Results were similar in the sensitivity analysis not censoring at the first ESA treatment. CONCLUSION:Our longitudinal analysis in patients with CKD not on ESA therapy highlights a stronger association between anaemia and increased hazard of MACE+ in women than in men. This sex difference should inform the design of trials addressing anaemia correction in CKD.

Background:Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs), including tryptophan-derived metabolites such as kynurenine (KYN), indoxyl sulfate (IS), and indole-3-acetic acid (IAA). IS has been identified as a potential contributor to cognitive impairment (CI), whereas less is known about the other tryptophan metabolites. We aimed to evaluate the association between these toxins related to tryptophan metabolism and CI in patients with CKD. Methods:Three thousand thirty-three patients with CKD stages 2-5 enrolled in CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort. Patients with both UT measurement and cognitive function screening [with mini-mental state examination (MMSE)] were included. CI was defined as an MMSE score ≤ 26/30. Logistic regression was used to assess the association between the studied UTs and MMSE. Results:Of the 2389 included patients [mean (SD) age: 66.5 (12.8) years, 66% males, mean (SD) estimated glomerular filtration rate (eGFR) 34.8 (13.4) ml/min/1.73 m2], 858 patients (35.9%) had an MMSE score ≤26/30. After adjustment for sociodemographic factors, cardiovascular risk factors, cerebrovascular disease, current depression, eGFR, urinary albumin-to-creatinine ratio, and UTs known to be associated with CI, no significant association was found between KYN or IAA and MMSE ≤26/30, whereas IS was significantly associated [Odds Ratio (OR), 95% confidence interval: 1.11 (1.00-1.21)]. Conclusion:Among tryptophan-derived metabolites studied, IS was associated with CI in patients with CKD, in contrast to KYN and IAA. Despite sharing a common origin, the UTs studied follow distinct metabolic pathways with different effects, highlighting the need for further investigation of the tryptophan pathway on CI in CKD.

Background Cognitive impairment (CI) affects self-management in chronic diseases, leading to poor decision-making, delayed care, and increased mortality. The specific impact of CI on adverse outcomes in CKD remains poorly explored. Methods The french CKD-REIN cohort included 3033 patients with CKD stage 2–5 and 5 years of follow-up. CI was assessed using the Mini-Mental State Examination (MMSE), and eGFR was estimated with the CKD-EPI creatinine equation. Cox models evaluated the risks of all-cause mortality, kidney replacement therapy (KRT) initiation, and major adverse cardiovascular (CV) events (MACEs). Results 3004 patients were included in the analysis (mean age: 67 years, mean eGFR 34 mL/min/1.73 m2), and 64%, 23% and 13% respectively had MMSE scores of >26, between 24-26, and <24 at baseline. During the follow-up period (mean: 3.87 years), 21.5% patients initiated KRT, 13.4% died, and 15.3% experienced a MACE before KRT or non-CV death. In adjusted Cox models, patients with a MMSE <24 had a higher risk of clinical adverse outcome, relative to those with a MMSE >26: HR [95% confidence interval] was 1.42 [1.12, 1.81], 1.57 [1.19, 2.07], and 1.32 [1.02, 1.70] for KRT initiation, all-cause mortality and MACE respectively. CI was associated with all-cause mortality in the MMSE 24-26 group also (HR: 1.45 [1.15, 1.83]). Conclusion In CKD, a baseline MMSE score <24 predicts higher overall-death, KRT initiation, and MACEs, relative to a baseline score >26. These results highlight CI’s prognostic value, and suggest that earlier detection could better personalize management, particularly for kidney and CV complications.

The transition from advanced chronic kidney disease (CKD) to kidney failure requires comprehensive management to optimize patient outcomes. This crucial period, in practical terms defined by CKD stages G4 and G5, involves complex decision-making regarding kidney replacement therapy, pre-emptive kidney transplantation and conservative kidney management. Patient preferences, quality of life, and comorbidities, especially cardiovascular disease, are essential considerations when making treatment decisions. Importantly, nephroprotective therapies should be continued even at advanced stages of CKD to stabilize kidney function and prevent cardiovascular events. Pre-emptive kidney transplantation, when feasible, offers the best outcomes and should be prioritized. Dialysis initiation should be based on clinical symptoms and shared decision-making with the patient, rather than laboratory values alone. For some, particularly older, patients with substantial comorbidities, conservative kidney management, emphasizing symptom management without kidney replacement therapy, might be preferred. Considerable disparities in access to care exist globally, especially in low- and middle-income countries, highlighting the need for tailored strategies. Registry and cohort studies have provided most of the scientific understanding in this area, but more randomized clinical trials are needed to guide advanced CKD management.

Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.

Un faisceau d’argument tend à démontrer l’existence d’un axe rein–cerveau expliquant le déclin cognitif observé dans des situations de maladie rénale chronique (MRC). L’évolution démographique actuelle devrait voir ces deux atteintes augmenter en nombre absolu et relatif. Dans cette revue narrative, nous proposons d’explorer les données épidémiologiques de l’association entre maladie rénale et santé neurocognitive ; l’existence d’un profil cognitif MRC-spécifique ; les mécanismes physiopathologiques en jeu ; les conséquences sur la démarche diagnostique et certains aspects thérapeutiques. Les données épidémiologiques convergent vers la confirmation d’un lien spécifique entre MRC et cognition. Les fonctions exécutives semblent fréquemment atteintes sans pouvoir dégager un phénotype cognitif MRC-spécifique. La physiopathologie ne se limite pas à l’axe vasculaire mais fait intervenir plusieurs mécanismes interdépendants avec un rôle-clé des toxines urémiques accumulés dans la MRC. La démarche diagnostique des deux atteintes nécessite une attention rigoureuse aux choix des marqueurs et à la qualité de leur mesure. Les approches thérapeutiques regroupent des axes médicamenteux et non médicamenteux. La complexité de l’axe rein–cerveau nécessite une recherche plus large faisant intervenir la collaboration de différents acteurs (patients, soignants, néphrologues, neurologues, gériatres, radiologues, et scientifiques fondamentaux).

Chronic kidney disease (CKD), defined per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines by persistent (≥3 months) abnormalities of kidney structure or function, including reduced estimated glomerular filtration rate (eGFR) and/or albuminuria, affects 10%-15% of adults worldwide and is a powerful, independent risk factor for cardiovascular diseases, including heart failure (HF). In CKD (stages G1-G3), particularly when accompanied by albuminuria (KDIGO stages A2-A3), even mild reductions in eGFR are associated with subclinical cardiac abnormalities-left ventricular hypertrophy, concentric remodelling, LV diastolic dysfunction, HF with preserved ejection fraction, and arrhythmias. Many CKD patients meet criteria for Stage B HF within the contemporary 'pre-HF' framework, based on structural and functional cardiac alterations and elevated biomarkers in the absence of symptoms. Detection is here challenging, as symptoms are non-specific and circulating biomarkers are confounded by reduced renal clearance. Echocardiography, including speckle-tracking techniques and emerging indices, and cardiac magnetic resonance imaging with tissue characterization and strain analysis are sensitive tools for early diagnosis and risk stratification, but routine screening is not currently recommended in asymptomatic CKD. This condition may be mitigated by aggressive control of traditional and CKD-specific risk factors, and therapies with proven cardiorenal benefits-SGLT2 inhibitors, finerenone, diuretics, renin-angiotensin system blockers, and selected GLP-1 receptor agonists-guide HF prevention. Future research should test cost-effective early diagnostic strategies, clarify the role of imaging and biomarkers in guiding therapy, and exploit multiomics and artificial intelligence to unravel mechanistic heterogeneity and enable personalized prevention of HF in early CKD.

OBJECTIVE:The aim of this French physician initiated, multicentre, prospective, randomised trial with blinded criteria for re-intervention was to evaluate the efficacy of paclitaxel coated balloons (DCBs) for the treatment of arteriovenous fistula stenosis. METHODS:One hundred and fifty patients with an arteriovenous fistula stenosis were included, and 145 were randomised 1:1 in the Angioplastie au Ballon Imprégné de paclitaxel vs. angioplastie Standard pour le traitement des Sténoses sur fistule artérioveineuse trial; ClinicalTrials.gov identifier: NCT02753998 (ABISS) between a DCB (Lutonix, BD, Franklin Lakes, NJ, USA) and a placebo balloon. The main outcome was the rate of primary patency loss at 6 months. The primary analysis was performed in the modified intention to treat population. Missing outcome data were handled using a conservative imputation approach. The per-protocol analysis excluded patients who were included by mistake, not treated according to the randomisation arm, lost to follow up, or who missed a visit. RESULTS:In the modified intention to treat analysis, there was no significant difference between the groups regarding primary patency loss at 6 months (31% [22 of 70] in the DCB group vs. 42% [30 of 71] in the placebo group; p = .090; hazard ratio = 0.62 [95% confidence interval {CI} 0.36 - 1.07]). Primary patency loss was lower in the DCB than in the placebo group at 3 months (4.2% vs. 22.5%; p = .002; hazard ratio = 0.18 [95% CI 0.05 - 0.60]), but not at 12 months (58.6% vs. 57.7%; p = .57; hazard ratio = 0.88 [95% CI 0.57 - 1.35]). In the per-protocol analysis, the primary patency loss was significantly lower in the DCB group than in the placebo group (26% [16 of 61] in the DCB group vs. 50% [28 of 56] in the placebo group; p = .004). CONCLUSION:In the ABISS trial, the use of a DCB was not superior to a placebo balloon at 6 months in the modified intention to treat analysis.

CONTEXT:Obesity is an independent risk factor for chronic kidney disease, and accurate estimation of the glomerular filtration rate (GFR) is crucial. However, limited data are available on the performance of the European Kidney Function Consortium (EKFC) equation in individuals with overweight or obesity. OBJECTIVE:To evaluate the performance of the EKFC equation by comparing its estimated GFR (eGFR) to values obtained from the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and machine learning (ML) models. METHODS:We compared the models using measured GFR (mGFR, obtained via plasma iohexol clearance) as a reference standard in a cohort of patients with overweight or obesity. We calculated the median bias (eGFR minus mGFR) and the concordance correlation coefficient for each method. RESULTS:The non-indexed EKFC equation exhibited the highest median bias (-4.80 mL/min, 95% CI: -7.49 to -2.92), particularly in patients with overweight (-7.81 mL/min, 95% CI: -12.87 to -4.80) and obesity (-4.57 mL/min, 95% CI: -8.57 to -1.72), with lower bias in healthy BMI individuals (-2.50 mL/min, 95% CI: -6.85 to 2.23). The EKFC equation showed lower concordance with mGFR than both the CKD-EPI 2021 equation and ML models and was the least accurate for CKD stage classification in patients with obesity, particularly those with hyperfiltration. CONCLUSION:In patients with overweight or obesity, the EKFC equation performed worse than the ML-based models and the CKD-EPI 2021 equation despite limitations of the latter in European populations. Our findings highlight the need for more accurate GFR estimation in this population, optimization of these models, and their validation in larger, more diverse cohorts.

Chronic kidney disease (CKD) affects >10% of the global adult population and is associated with substantial cardiovascular morbidity and mortality. Sudden cardiac death (often precipitated by ventricular arrhythmias like torsades de pointes) is a leading cause of death in patients with CKD. Prolongation of the QT interval (a marker of delayed ventricular repolarization) is a significant risk factor for arrhythmia in patients with CKD, whether they are on dialysis or not. QT prolongation in CKD is multifactorial and may result from electrolyte imbalances, myocardial remodelling, autonomic dysfunction and exposure to QT-prolonging drugs. Patients on haemodialysis are particularly vulnerable to QT prolongation due to rapid intradialytic electrolyte and fluid shifts. Many drugs known to prolong the QT interval (including various selective serotonin reuptake inhibitors, antibiotics, antiemetics and antipsychotics) are frequently prescribed to patients with CKD, even though there are few data on their safety in this population. The results of several well-designed pharmaco-epidemiological analyses (all based on data from the US Renal Data System) have shown associations between QT-prolonging drugs and an elevated risk of sudden cardiac death among patients on dialysis. These findings are concerning, given the widespread use of such drugs. The objective of this narrative review is to critically evaluate the pathophysiological relevance, prevalence and cardiovascular consequences of QT-prolonging drug use in the CKD setting.

Hyperpolypharmacy (≥ 10 daily medications) is frequent in patients with chronic kidney disease (CKD), but its impact remains poorly characterized. This study, based on 3,011 non-dialyzed, non-transplant CKD outpatients from the CKD-REIN cohort (eGFR < 60 mL/min/1.73 m2) aimed to describe drug burden and assess associations between hyperpolypharmacy and adverse outcomes. Drug prescription, kidney function, adverse drug reactions (ADRs), hospitalizations, kidney replacement therapy and deaths before KRT were prospectively recorded over five years. Median age was 69 years and mean eGFR was 34 mL/min/1.73 m2. At baseline, 80