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Incidence of kidney replacement therapy (KRT) varies widely across countries. Its relations to individual characteristics, nephrology practices for slowing chronic kidney disease (CKD) progression, and KRT access remain unclear.We investigated intercountry differences in kidney failure (KF) rate, defined by a sustained estimated glomerular filtration rate (eGFR) 15 ml/min per 1.73 mAmong 7381 patients with CKD stage 3 to 4 at enrollment, 1297 progressed to KF and 947 initiated KRT over a 3-year follow-up period. Compared to the United States, demographic-adjusted and eGFR-adjusted hazard ratios (HRs) (HRs, 95% confidence intervals [CI]) for a sustained low eGFR were 0.77 (95% CI, 0.57-1.02) in Brazil, 0.90 (95% CI, 0.75-1.08) in France, and 1.03 (95% CI, 0.86-1.03) in Germany. Further adjustment for comorbidities, albuminuria, systolic BP, and RAASi prescription did not substantially change these HRs. In contrast, compared with the United States, the fully-adjusted HR for KRT remained significantly lower in Brazil (0.55, 95% CI 0.39-0.79), higher in Germany (95% CI, 1.36, 1.09-1.69), and similar in France (95% CI, 1.07, 0.81-1.39).Individual risk factors for CKD progression in nephrology patients appeared to explain most intercountry variations in KF but not KRT incidence. This suggests a prominent role for differences in practices related to KRT initiation or access, but not those for slowing disease progression. This study also shows that using KRT as a KF surrogate may bias estimates of associations with CKD progression risk factors.

BackgroundCatheter-related bloodstream infections (CRBIs) remain a major cause of mortality in haemodialysis (HD) patients with central venous catheters (CVCs), especially because of the non-specific symptomatology and the delay in microbiological diagnosis with possible use of non-optimal empiric antibiotics. Moreover, empiric broad-spectrum antibiotics increase antibiotic resistance development. This study aims to evaluate the diagnostic performance of real-time polymerase chain reaction (rt-PCR) in suspected HD CRBIs compared with blood cultures.MethodsA blood sample for rt-PCR was collected simultaneously with each pair of blood cultures for suspected HD CRBI. The rt-PCR was performed on the whole blood, without any enrichment stage and with specific DNA primers: 16S (universal bacterial), Staphylococcus spp., Staphylococcus aureus and mecA. Each successive patient with a suspected HD CRBI in the HD centre of Bordeaux University Hospital was included. Performance tests were used to compare the result obtained in each rt-PCR assay with its corresponding routine blood culture.ResultsEighty-four paired samples were collected and compared for 40 suspected HD CRBI events in 37 patients. Among these, 13 (32.5%) were diagnosed as HD CRBI. All rt-PCRs except mecA (insufficient number of positive samples) showed high diagnostic performances within 3.5 h: 16S (sensitivity 100%, specificity 78%), Staphylococcus spp. (sensitivity 100%, specificity 97%), S. aureus (sensitivity 100%, specificity 99%). Based on the rt-PCR results, antibiotics could be more appropriately targeted, thus cutting anti-cocci Gram-positive therapy from 77% to 29%.ConclusionsThe performance of rt-PCR in suspected HD CRBI events showed fast and high diagnostic accuracy. Its use would improve HD CRBI management with an antibiotic consumption decrease.

Background Mitochondrial functions are controlled by genes of both mitochondrial and nuclear DNA. Pathogenic variants affecting any of these are responsible for primary mitochondrial disorders (MIDs), which can be diagnosed during adulthood. Kidney functions are highly dependent on mitochondrial respiration. However, the prevalence of MID-associated nephropathies (MIDANs) is unknown in the adult population. We aimed to address this point and to provide a full characterization of MIDANs in this population. Methods We retrospectively included for observational study adults (≥16 years of age) with genetically diagnosed MID between 2000 and 2020 in our tertiary care academic centre when they had a chronic kidney disease (CKD) evaluation. MIDANs were ascertained by CKD occurring in MIDs. The phenotypic, biological, histopathological and genotypic characteristics were recorded from the medical charts. Results We included 80 MID-affected adults and ascertained MIDANs in 28/80 (35%). Kidney diseases under the care of a nephrologist occurred in only 14/28 (50%) of the adults with MIDAN. MIDANs were tubulointerstitial nephropathy in 14/28 patients (50%) and glomerular diseases in 9/28 (32.1%). In adults with MID, MIDAN was negatively associated with higher albumin levels {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.67–0.95]} and vision abnormalities [OR 0.17 (95% CI 0.03–0.94)] and positively associated with hypertension [OR 4.23 (95% CI 1.04–17.17)]. Conclusion MIDANs are frequent among adult MIDs. They are mostly represented by tubulointerstitial nephropathy or glomerular disease. Vision abnormalities, hypertension and albumin levels were independently associated with MIDANs. Our results pave the way for prospective studies investigating the prevalence of MIDANs among undetermined kidney disease populations.

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine levels, reduced urine output or both. Death may occur in 16–49% of patients admitted to an intensive care unit with severe AKI. Complex arrhythmias are a potentially serious complication in AKI patients with pre-existing or AKI-induced heart damage and myocardial dysfunction, with fluid overload, especially electrolyte and acid–base disorders, representing the pathogenetic mechanisms of arrhythmogenesis. Cardiac arrhythmias, in turn, increase the risk of poor renal outcomes, including AKI. Arrhythmic risk in AKI patients receiving kidney replacement treatment may be reduced by modifying dialysis/replacement fluid composition. The most common arrhythmia observed in AKI patients is atrial fibrillation. Severe hyperkalaemia, sometimes combined with hypocalcaemia, causes severe bradyarrhythmias in this clinical setting. Although the likelihood of life-threatening ventricular arrhythmias is reportedly low, the combination of cardiac ischaemia and specific electrolyte or acid–base abnormalities may increase this risk, particularly in AKI patients who require kidney replacement treatment. The purpose of this review is to summarize the available epidemiological, pathophysiological and prognostic evidence aiming to clarify the complex relationships between AKI and cardiac arrhythmias.

Arteriovenous (AV) access choice has sparked controversy with recent evidence suggesting overestimation of benefits associated with AV fistula versus graft in certain populations. We assessed outcomes associated with first-line AV access type in patients who started hemodialysis with a catheter in France, overall and by subgroups of age, sex, and comorbidities. In this retrospective cohort study, we included incident patients who initiated hemodialysis with a catheter from 2010 through 2018, followed by the French REIN Registry. Our main exposure was the first-line (first-created) AV graft versus fistula, ascertained through the linkage with the French national health-administrative database. Outcomes were all-cause and cause-specific hospitalization, and all-cause mortality. We used joint frailty models to deal with recurrent hospitalizations and informative censoring by death, Cox proportional hazard (PH) models, and inverse probability weighting. From the 18,625 patients included (mean age was 68±15 years, 35% were women), 5% had a first-line AV graft. Patients with AV graft had an 11%-higher weighted hazard of all-cause hospitalization (95% CI 1.09 to 1.13), 16% higher weighted hazard of cardiovascular (95% CI 1.05 to 1.29) and infection-related (95% CI 1.01 to 1.33) hospitalization, 34% higher weighted hazard of vascular access-related hospitalization, and a 9%-higher weighted hazard of all-cause death (95% CI 0.97 to 1.23). Results were consistent for most subgroups, except that the highest hazard of hospitalization with AV graft was blunted in patients with comorbidities (i.e. diabetes, weighted HR of all-cause hospitalization 1.03, 95% CI 0.95-1.12).- To conclude, in patients starting hemodialysis with a catheter, first-line AV graft is associated with increased hazard of hospitalization vs. patients with AV fistula. This may, however, not be the case for patients with a poor vascular condition, i.e., those with diabetes, who have a similar hospitalization and mortality rates with either graft or fistula.

Background Acute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. Methods We used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3–5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013–20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. Results At baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight ( Conclusions The study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.

Background Conservative care is increasingly considered an alternative to kidney replacement therapy for kidney failure management, mostly among the elderly. We investigated its status and the barriers to its implementation from patients’ and providers’ perspectives. Methods We analysed data from 1204 patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) Results All participating facilities reported they were routinely able to offer conservative care, but only 37% had written protocols and only 5% had a person or team primarily responsible for it. Overall, 6% of patients were estimated to use conservative care. Among nephrologists, 82% reported they were fairly or extremely comfortable discussing conservative care, but only 28% usually or always offered this option for older (>75 years) patients approaching kidney failure. They used various terminology for this care, with conservative management and non-dialysis care mentioned most often. Among patients, 5% of those >75 years reported receiving information about this option and 2% preferring it. Conclusions Although reported by nephrologists to be widely available and easily discussed, conservative care is only occasionally offered to older patients, most of whom report they were not informed of this option. The lack of a person or team responsible for conservative care and unclear information appear to be key barriers to its implementation.

Purpose: We investigated the long-term safety and efficacy of hepatic transarterial embolization (TAE) in patients with symptomatic polycystic liver disease (PLD). Materials and Methods: A total of 26 patients were included, mean age of 52.3 years (range: 33–78 years), undergoing 32 TAE procedures between January 2012 and December 2019 were included in this retrospective study. Distal embolization of the segmental hepatic artery was performed with 300–500 µm embolic microspheres associated with proximal embolization using microcoils. The primary endpoint was clinical efficacy, defined by an improvement in health-related quality of life using a modified Short Form-36 Health Survey and improvement in symptoms (digestive or respiratory symptoms and chronic abdominal pain), without invasive therapy during the follow-up period. Secondary endpoints were a decrease in total liver volume and treated liver volume and complications. Results: Hepatic embolization was performed successfully in 30 of 32 procedures with no major adverse events. Clinical efficacy was 73% (19/26). The mean reduction in hepatic volume was −12.6% at 3 months and −27.8% at the last follow-up 51 ± 15.2 months after TAE (range: 30–81 months; both ps < 0.01). The mean visual analog scale pain score was 5.4 ± 2.8 before TAE and decreased to 2.7 ± 1.9 after treatment. Three patients had minor adverse events, and one patient had an adverse event of moderate severity. Conclusion: Hepatic embolization using microspheres and microcoils is a safe and effective treatment for PLD that improves symptoms and reduces the volume of hepatic cysts.

Late stages of CKD are characterized by significant symptom burden. This study aimed to identify subgroups within the 5-year trajectories of symptom evolution in patients with CKD and to describe associated patient characteristics and outcomes.Among 2787 participants (66% men) with eGFR60 ml/min per 1.73 mPatient mean age (±SD) at baseline was 67±13 years, and mean eGFR was 33±13 ml/min per 1.73 mThis study highlights a significant worsening of symptoms in about one third of the participants, whereas the majority reported low symptom severity throughout the study.

BACKGROUND AND AIMS Men are at higher risk of cardiovascular disease (CVD) than women in the general population, and chronic kidney disease (CKD) is a well-established cardiovascular (CV) risk factor [1–4]. However, the incidence of cause-specific CV events in men and women with CKD is poorly documented. METHOD All hospitalization and death reports for CV events of the 3033 patients (1983 men and 1050 women) with non-dialysis CKD (stage 3–5) included in the French CKD-REIN Cohort were reviewed and classified by cause using criteria from the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [5]. Cause-specific Cox proportional hazard models were used to estimate hazard ratios for death and each fatal or nonfatal CV event according to gender. RESULTS At baseline, in men (mean age: 68 years; mean eGFR 33 mL/min/1.73 m²), the prevalence of atheromatous CVD was 30% for coronary artery disease, 14% for cerebrovascular disease and 17% for lower limb artery disease, and that of non-atheromatous CVD was 14% for heart failure and 13% for atrial fibrillation. In women (65 years old, 32 mL/min/1.73 m²), these prevalences were 15%, 7%, 9%, 11% and 9%, respectively. During a median follow-up of 5 (IQR: 3–5) years, 98 men and 43 women died from CVD {i.e. 1.3 [95% confidence interval (95% CI): 1.0–1.5] versus 1.0 (0.7–1.3)/100 person-years}, including 53% versus 46% from heart failure, 31% versus 19% from sudden death, and 16% versus 35% from other cardiovascular causes, respectively. Crude incidence rates of death or hospitalization for coronary artery disease and lower limb artery disease were higher in men than in women, slightly higher for CV death, cerebrovascular disease and atrial fibrillation, but similar for both genders for heart failure (Fig. 1). History of CVD was strongly associated with subsequent CV events of any type. In multivariable analyses, gender was no longer associated with any cause-specific CV event, whereas a lower eGFR was significantly associated with an increased risk of coronary artery disease and heart failure, but not with other CV events (Table 1). CONCLUSION In patients with moderate or advanced CKD, the burden of atheromatous CVD is higher in men than in women and explained by their higher prevalence of cardiovascular risk factors, but that for heart failure and atrial fibrillation appears to be similar for both genders.

BACKGROUND AND AIMS Chronic kidney disease (CKD) is a risk factor for cognitive impairment. In the general population, many risk factors have been reported in association with incident major neurocognitive disorders. The link between CKD and cognitive dysfunction is not completely understood; it may involve different mechanisms such as vascular dysfunction or uremic toxin toxicity. We aimed to assess the influence of cardiovascular risk factors, cardiovascular disease and depression on the association between kidney function and cognitive function in patients with CKD. METHOD We analyzed baseline data from 3033 patients with CKD stage 3–5 included in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort between 2013 and 2016. Cognitive function was assessed with the Mini Mental State Examination (MMSE), and the glomerular filtration rate was estimated with the CKD EPI formula. We applied unadjusted and adjusted linear and logistic regression models, with the MMSE score as a continuous or categorical variable (at a cut-off point at 24/30). RESULTS The mean patient age was 66.8, the mean estimated glomerular filtration rate (eGFR) was 33 mL/min/1.73 m2 and 393 patients (13.0%) had a MMSE score The eGFR was positively associated with the MMSE score before and after adjustment for age, sex, education level, cardiovascular risk factors, cardiovascular disease and depression, giving point increases in the MMSE score of 0.24 (0.15–0.33; P < .001) and 0.14 (0.04–0.23; P = .006) for a 10 mL/min/1.73 m2 increment in the eGFR, respectively. Other risk factors significantly associated with a lower MMSE score in multivariate analysis were age, female sex, lower educational level, diabetes, obesity, cerebrovascular disease, atrial fibrillation and CES-D-10 score. The eGFR was associated with a low MMSE score (defined as MMSE score CONCLUSION In a cohort of well-phenotyped patients with CKD, lower eGFR is associated with worse cognitive function, independent of age, sex, educational level, cardiovascular injury and depression.

BACKGROUND AND AIMS Elevated serum urea levels are common in moderate-to-advanced CKD. Several studies have shown that urea is a direct and indirect uremic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before kidney replacement therapy (KRT) in patients with CKD. METHOD CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 RESULTS Of the 2507 included patients {median [first quartile–third quartile (Q1–Q3)] age: 69 (61–77); mean (standard deviation) eGFR 33.5(11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. Over a median follow-up of 3.0 years [Q1–Q3, 2.2–3.1], 451 experienced their first atheromatous or nonatheromatous cardiovascular event (fatal or nonfatal), leading to an incidence rate (IR) [95% confidence interval (95% CI)] of 7.1 (6.4–7.7)/100 person-years (PYs) (Fig. 1). Over a median follow-up period of 4.8 (3.3–5.1) years, 407 patients died before KRT, leading to an IR of 4.0 (3.6–4.3)/100 PYs. After multiple adjustments for cardiovascular risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and nonatheromatous cardiovascular events than patients in T1 [HR (95% CI), 2.08 (1.50–2.88), Fig. 1]. A nonsignificant trend towards a higher risk was also noted for patients in T2 [1.28 (0.96–1.71)]. The adjusted HRs for death before KRT were 1.30 (0.96–1.75] and 1.73 (1.22–2.45) for patients in T2 and those in T3, respectively. CONCLUSION Beyond CV risk factors including eGFR, this hypothesis-generating study suggests that serum urea level is a predictor of cardiovascular outcomes in patients with moderate to advanced CKD. Further research is needed to confirm current findings and explore mechanisms.

BACKGROUND AND AIMS Vascular access choice for patients with high risk of arteriovenous (AV) access failure has been sparking growing controversy as recent studies show similar survival and morbidity across patients receiving arteriovenous (AV) fistula or graft. We assessed hospitalization and mortality risks associated with access type in patients who started hemodialysis with a catheter without previous AV access creation in France, overall and by subgroups of age, sex and comorbidities. METHOD Longitudinal study of 18 800 incident hemodialysis patients from 2010 through 2018, based on the linkage of the French REIN registry of kidney replacement therapy (KRT) with the national health administrative database (SNDS). First-line AV access (fistula or graft) was ascertained from SNDS procedures codes. Hospitalizations were also identified through the SNDS, whereas mortality data was obtained from the REIN Registry. We used joint frailty models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of recurrent hospitalization and death associated with AV grafts, compared with AV fistulæ. These models accounted for dependence between hospitalization and death. We further estimated propensity scores for first-line AV graft placement and used inverse probability weighting (IPW) to obtain weighted HR (wHR), accounting for potential indication bias. RESULTS Among studied patients, 35% were women, 45% had diabetes, 26% had history of heart failure and 19% had history of peripheral artery disease. More than half started dialysis urgently (52%). Patients with first-line AV graft (5%) were older than those with AV fistula (72 ± 14 versus 68 ± 15 years, respectively), and required more frequently assistance to walk (29% versus 17%). IPW resulted in covariate balance (absolute standardized difference CONCLUSION In patients starting hemodialysis with a catheter without previous AV access creation, the fistula first approach is associated with similar mortality, but lower risk of hospitalization compared to first-line AV graft. This may, however, not be the case for patients with a poor vascular condition, i.e. those with diabetes or peripheral artery disease, who have a similar hospitalization risk with either graft or fistula.

Background The lack of a well-designed prospective study of the determinants of urgent dialysis start led us to investigate its individual- and provider-related factors in patients seeing nephrologists. Methods The Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study that included 3033 patients with CKD [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from 40 nationally representative nephrology clinics from 2013 to 2016 who were followed annually through 2020. Urgent-start dialysis was defined as that ‘initiated imminently or Results Over a 4-year (interquartile range 3.0–4.8) median follow-up, 541 patients initiated dialysis with a known start status and 86 (16%) were identified with urgent starts. The 5-year risks for the competing events of urgent and non-urgent dialysis start, pre-emptive transplantation and death were 4, 17, 3 and 15%, respectively. Fluid overload, electrolytic disorders, acute kidney injury and post-surgery kidney function worsening were the reasons most frequently reported for urgent-start dialysis. Adjusted odds ratios for urgent start were significantly higher in patients living alone {2.14 [95% confidence interval (CI) 1.08–4.25] or with low health literacy [2.22 (95% CI 1.28–3.84)], heart failure [2.60 (95% CI 1.47–4.57)] or hyperpolypharmacy [taking >10 drugs; 2.14 (95% CI 1.17–3.90)], but not with age or lower eGFR at initiation. They were lower in patients with planned dialysis modality [0.46 (95% CI 0.19–1.10)] and more nephrologist visits in the 12 months before dialysis [0.81 (95% CI 0.70–0.94)] for each visit. Conclusions This study highlights several patient- and provider-level factors that are important to address to reduce the burden of urgent-start dialysis.

Background: Genome-wide association studies have revealed robust associations of common genetic polymorphisms in an intron of the PHACTR-1 (phosphatase and actin regulator 1) gene (chr6p24), with cervical artery dissection, spontaneous coronary artery dissection, and fibromuscular dysplasia. The aim was to assess its role in the pathogenesis of cervical artery dissection or fibromuscular dysplasia. Methods: Using various tissue-specific Cre-driver mouse lines, Phactr1 was deleted either in endothelial cells using 2 tissue-specific Cre-driver (PDGFB [platelet-derived growth factor B]-Cre ERT2 mice and Tie2 [tyrosine kinase with immunoglobulin and EGF homology domains]-Cre) and smooth muscle cells (smooth muscle actin-Cre ERT2 ) with a third tissue-specific Cre-driver. Results: To test the efficacy of the Phactr1 deletion after cre-induction, we confirmed first, a decrease in Phactr1 transcription and Phactr1 expression in endothelial cell and smooth muscle cell isolated from Phactr1 iPDGFB and Phactr1 iSMA mice. Irrespective to the tissue or the duration of the deletion, mice did not spontaneously display pathological phenotype or vascular impairment: mouse survival, growth, blood pressure, large vessel morphology, or actin organization were not different in knockout mice than their comparatives littermates. Challenging vascular function and repair either by angiotensin II–induced hypertension or limb ischemia did not lead to vascular morphology or function impairment in Phactr1-deleted mice. Similarly, there were no more consequences of Phactr1 deletion during embryogenesis in endothelial cells. Conclusions: Loss of PHACTR-1 function in the cells involved in vascular physiology does not appear to induce a pathological vascular phenotype. The in vivo effect of the intronic variation described in genome-wide association studies is unlikely to involve downregulation in PHACTR-1 expression.

Background Patients suffering from acute kidney injury(AKI) in the intensive care unit (ICU) can have various renal trajectories and outcomes. Aims were to assess the various clinical trajectories after AKI in the ICU and to determine risk factors for developing chronic kidney disease (CKD). Methods We conducted a prospective 5-year follow-up study in a medical ICU at Bordeaux University Hospital (France). The patients who received invasive mechanical ventilation, catecholamine infusion or both and developed an AKI from September 2013 to May 2015 were included. In the Cox analysis, the violation of the proportional hazard assumption for AKD was handled using appropriate interaction terms with time, resulting in a time-dependent hazard ratio (HR). Results A total of 232 patients were enrolled, with an age of 62 ± 16 years and a median follow-up of 52 days (interquartile range 6–1553). On day 7, 109/232 (47%) patients progressed to acute kidney disease (AKD) and 66/232 (28%) recovered. A linear trajectory (AKI, AKD to CKD) was followed by 44/63 (70%) of the CKD patients. The cumulative incidence of CKD was 30% [95% confidence interval (CI) 24–36] at the 5-year follow-up. In a multivariable Cox model, in the 6 months following AKI, the HR for CKD was higher in AKD patients [HR 29.2 (95% CI 8.5–100.7); P Conclusion There were several clinical trajectories of kidney disease after ICU-acquired AKI. CKD risk was higher in AKD patients only in the first 6 months. Lack of renal recovery rather than AKD per se was associated with the risk of CKD.

Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR.

IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer.We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study.Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV.Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

International audience; Objective: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. Design and Methods: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study–participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. Conclusion: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract

Anorexia nervosa is a condition associated with poor outcomes in a variety of circumstances such as recurrence of eating disorders, psychiatric disorders, and organ damage. In the present study, we first sought to determine the 5-year kidney graft survival in patients with anorexia nervosa and then to evaluate the BMI course and medical complications. In this multicenter, retrospective, case–control study, we analyzed the impact of anorexia nervosa on graft outcomes compared to transplant recipients with low or normal BMI. We enrolled 137 women in this study: 19 with anorexia nervosa, 59 with low BMI (BMI

International audience; RATIONALE & OBJECTIVE: Health-related quality of life (HRQoL) is a major outcome measure increasingly used in patients with chronic kidney disease (CKD). We evaluated the association between different stages of CKD and the physical and mental health domains of HRQoL.STUDY DESIGN: Cross-sectional study.SETTING & PARTICIPANTS: 2,693 outpatients with moderate (stage 3, estimated glomerular filtration rate [eGFR], 30-60mL/min/1.73m2) or advanced (stages 4-5, estimated glomerular filtration rate40% of those with advanced CKD or receiving dialysis, 12% with a functioning transplant, and 3% of the general population sample. HRQoL physical scores (adjusted for age, sex, education, obesity, and diabetes) were significantly lower in patients in all CKD subgroups than in the general population. For patients receiving dialysis, the magnitude of the difference in physical score versus the general population exceeded 4.5 points, the minimal clinically important difference for this score in this study; for both kidney transplant recipients and patients with advanced CKD, the magnitude of the difference was close to this threshold. For mental score, only dialysis patients had a score that differed from that of the general population by more than the minimal clinically important difference.LIMITATIONS: Cross-sectional study design for each subpopulation.CONCLUSIONS: This study highlights the degree to which perceived physical health is lower in the setting of CKD than in the general population, even in the absence of kidney failure, and calls for greater attention to CKD-related quality of life.

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear. Here, we studied the control by CD154 of the proinflammatory cytokine interleukin- (IL-) 6 secretion in short-term oxygen (O2) deprivation conditions, using the HK-2 cell line as a kidney tubular epithelial cell (TEC) model. IL-6 secretion was markedly stimulated by CD154 after 1 to 3 hours of hypoxic stress. Both intracellular IL-6 expression and secretion were stimulated by CD154 and associated with a strong upregulation of IL-6 mRNA and increased transcription. Searching for inhibitors of CD154-mediated IL-6 production by HK-2 cells in hypoxic conditions, we observed that chloroquine, a drug that has been repurposed as an anti-inflammatory agent, alleviated this induction. Therefore, CD154 is a potent early stimulus for IL-6 secretion by TECs in O2 deprivation conditions, a mechanism likely to take part in the deleterious inflammatory consequences of platelet activation in kidney tubular injury. The inhibition of CD154-induced IL-6 production by chloroquine suggests the potential usefulness of this drug as a therapeutic adjunct in conditions associated with acute kidney injury.