External validation of the 2-year mortality prediction tool in hemodialysis patients developed using a Bayesian network.

Background: In recent years, a number of predictive models have appeared to predict the risk of medium-term mortality in hemodialysis patients, but only one, limited to patients aged over 70 years, has undergone sufficiently powerful external validation. Recently, using a national learning database and an innovative approach based on Bayesian networks and 14 carefully selected predictors, we have developed a clinical prediction tool to predict all-cause mortality at 2 years in all incident hemodialysis patients. In order to generalize the results of this tool and propose its use in routine clinical practice, we carried out an external validation using an independent external validation database. Methods: A regional, multicenter, observational, retrospective cohort study was conducted to externally validate the tool for predicting 2-year all-cause mortality in incident and prevalent hemodialysis patients. This study recruited a total of 142 incident and 697 prevalent adult hemodialysis patients followed up in one of the eight Association pour l'Utilisation du Rein Artificiel dans la région Lyonnaise (AURAL) Alsace dialysis centers. Results: In incident patients, the 2-year all-cause mortality prediction tool had an area under the receiver curve (AUC-ROC) of 0.73, an accuracy of 65%, a sensitivity of 71% and a specificity of 63%. In prevalent patients, the performance for the external validation were similar in terms of AUC-ROC, accuracy and specificity, but was lower in term of sensitivity. Conclusion: The tool for predicting all-cause mortality at 2 years, developed using a Bayesian network and 14 routinely available explanatory variables, obtained satisfactory external validation in incident patients, but sensitivity was insufficient in prevalent patients.

Primary aldosteronism without hypertension:A case report and review of the literature / Hyperaldostéronisme primaire sans hypertension artérielle : à propos d'un cas et revue de la littérature

We describe the case of a patient who presented with hyperaldosteronism without arterial hypertension. She had been referred for consultation for persistent severe hypokalaemia despite oral KCl supplementation. The absence of hypertension had been proven by repeated clinical measurements and by ABPM. Hyperaldosteronism had been demonstrated by hormonal assays and catheterization of the adrenal veins. Abdominal CT revealed a left adrenal adenoma. Finally, the anatomopathological examination of the surgical specimen confirmed the adenoma. After the intervention, serum potassium normalized. The clinical case is completed by a review of the literature of hyperaldosteronisms without arterial hypertension.

Nous décrivons le cas d'une patiente qui s'est présentée avec un hyperaldostéronisme sans hypertension artérielle. Elle a été adressée en consultation pour une hypokaliémie sévère persistante malgré une supplémentation orale en chlorure de potassium (KCl). L'absence d'hypertension a été prouvée par des mesures cliniques répétées et par mesure ambulatoire de la pression artérielle (MAPA). L'hyperaldostéronisme a été mis en évidence par des dosages hormonaux et un cathétérisme des veines surrénales. Le scanner abdominal a révélé un adénome surrénalien gauche. Enfin, l'examen anatomopathologique de la pièce opératoire a confirmé l'adénome. Après l'intervention, le potassium sérique s'est normalisé. Le cas clinique est complété par une revue de la littérature des hyperaldostéronismes sans hypertension artérielle.

Protective antibody response to mRNA-1273 and BNT162b2 vaccines in patients on maintenance haemodialysis: a prospective cohort study.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is more frequent and severe in patients with chronic kidney disease (CKD) on maintenance haemodialysis (HD). Vaccines are now available, but the protective response rates and determinants of humoral response to the vaccine are poorly described. Methods: This prospective observational study describes the response rates of detectable and protective antibody titres 1 month after each dose of an mRNA vaccine in a cohort of 851 patients on maintenance HD. Findings: Among naïve SARS-CoV-2 patients, a vast majority produced detectable (95.2%) or protective levels of antibodies (69.6%) 1 month after the second vaccine dose. In addition, the response rate was significantly higher with the mRNA-1273 than with the BNT162b2 vaccine 1 month after the second dose (79.8 versus 59.1%, respectively; P < 0.001). The main determinants for an inadequate humoral response were older age, treatment with immunosuppressants or oral anticoagulants and low serum albumin. All the patients who encountered coronavirus disease 2019 before vaccination also reached a highly protective humoral response. Interpretation: We found an acceptable humoral response rate in patients on maintenance HD, much higher than in transplant recipients. Therefore the third dose of vaccine may be justified in those patients with an inadequate humoral response, particularly those with a history of organ transplantation or immunosuppressive treatment.

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort.

BACKGROUND: The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case-control cohort and test the pertinence of the proposed thresholds. METHODS: A retrospective case-control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3-5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone. RESULTS: 314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48-0.79; and OR 0.72, 95% CI 0.59-0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02-1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60-0.72, p = 0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60-0.72, p = 0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64-0.76, p = 0.526). A 40% and 20% score thresholds were not superior to eGFR < 15 and 20 mL/min/1.73 m2, respectively. A 10% threshold was more specific than an eGFR < 30 mL/min/1.73 m2. CONCLUSION: KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

OBJECTIVE: Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. METHODS: Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. RESULTS: Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. CONCLUSION: In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

Blood pressure control in patients with chronic kidney disease according to office and home blood pressures.

OBJECTIVES: The aim of this study was to assess blood pressure (BP) control in patients with chronic kidney disease (CKD) according to office and home BP and to assess the prevalence of normal BP, white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and elevated BP. METHODS: Patients with renal failure with or without proteinuria were included in this multicenter observational study. Office BP was first measured by the physician using a self-monitoring BP device (three automatic readings), then by the patient at home (morning and evening) over 3 consecutive days. WUCH was defined as a systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mmHg in the clinic and SBP/DBP<135/85 mmHg at home. MUCH was defined as SBP/DBP <140/90 mmHg in the clinic and SBP/DBP ≥135/85 mmHg at home. RESULTS: Among the 243 included subjects, data of 225 patients were analyzed. Mean estimated glomerular filtration rate was 37.7 ± 15.7 mL/min/1.73 m and mean office SBP/DBP was 154 ± 19/83 ± 13 mmHg. Mean office SBP/DBP was significantly higher than home SBP/DBP (+9.0 ± 15.1/+7.0 ± 10.0 mmHg, P < 0.01). Normal BP (office and home BP), WUCH, MUCH and elevated BP (office and home BP) rates were 12.0, 14.2, 6.7 and 67.1%, respectively. The patients were taking, on average, 2.8 ± 1.5 antihypertensive drugs/day. CONCLUSION: BP control in patients with CKD was poor. Routine use of 'out-of-office' BP measurement, in addition to office BP by which we can identify patients with WUCH or MUCH, should be recommended based on the current findings.

Metabolic syndrome in haemodialysis patients: prevalence, determinants and association to cardiovascular outcomes.

BACKGROUND: In the general population, metabolic syndrome (MetS) is predictive of major adverse cardiovascular events (MACE). Waist circumference (WC), a component of the MetS criteria, is linked to visceral obesity, which in turn is associated with MACE. However, in haemodialysis (HD) patients, the association between MetS, WC and MACE is unclear. METHODS: In a cross-sectional study of 1000 HD patients, we evaluated the prevalence and characterised the clinical predictors of MetS. The relationship between MetS and its components, alone or in combination, and MACE (coronary diseases, peripheral arteriopathy, stroke or cardiac failure), was studied using receiver operating characteristics (ROC) curves and logistic regression. RESULTS: A total of 753 patients were included between October 2011 and April 2013. The prevalence of MetS was 68.5%. Waist circumference (> 88 cm in women, 102 cm in men) was the best predictor of MetS (sensitivity 80.2; specificity 82.3; AUC 0.80; p <  0.05). In multivariate analysis, MetS was associated with MACE (OR: 1.85; 95CI 1.24-2.75; p <  0.01), but not WC alone. There was a stronger association between the combination of abdominal obesity, hypertriglyceridaemia and low high-density lipoprotein cholesterol with MACE after exclusion of impaired fasting glucose and hypertension. CONCLUSIONS: MetS is frequent and significantly associated with MACE in our haemodialysis cohort and probably in other European dialysis populations as well. In HD patients, a new simplified definition could be proposed in keeping with the concept of the "hypertriglyceridaemic waist".

CERA conversion to darbepoetin alfa in 154 hemodialysis patients.

PURPOSE: Anemia is a common complication in dialysis patients, usually treated with erythropoietin (EPO). Among available EPOs and analogs, continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) are the only two agents with a long duration of action, although they have almost never been formally compared in terms of efficacy. We took advantage of an accidental disruption in CERA supply to study the effect of its replacement with DA in the same patients. METHODS: The clinical and biological characteristics of 154 hemodialysis patients were retrospectively reviewed during the last 3 months on CERA compared to the first 4 months after replacement by DA, both ASE being administered by IV route. The comparison included EPO doses, hemoglobin levels, factors interfering with anemia (iron status assessment, iron doses, inflammation, quality of treatment) and was performed under the Bayesian paradigm. RESULTS: We found no significant differences between the two EPOs in terms of doses or hemoglobin concentrations. Factors that could potentially influence hemoglobin concentrations also did not differ under CERA or DA. The stability of hemoglobin was identical with both EPOs. We provide a conversion factor which allows comparison of cost according to local prices. CONCLUSIONS: We conclude that, in this observational "real life" study, the two EPOs are to be considered as equivalent.

Variables linked to hepatitis B vaccination success in non-dialyzed chronic kidney disease patients: Use of a bayesian model.

BACKGROUND: Hepatitis B vaccination is recommended for chronic kidney disease (CKD) patients before starting dialysis. We performed an analyis aimed to describe the clinical and biological parameters related to the success of vaccination in CKD patients before starting dialysis. METHODS: We extracted data of 170 non-dialyzed patients who were offered hepatitis B vaccination from a register. They received a first vaccination of 40µg followed by boosters after one, two and six months. Patients were considered protected if their hepatitis B antibody level was >10IU/L, three months apart. A logistic regression and a Bayesian model were used to describe the relationships between variables and the success of vaccination. RESULTS: Vaccination protected 50.6% of the patients. Model adjustment to the data was higher using the Bayesian model compared to the logistic regression (with area under the ROC curve of 0.955±0.007 vs 0.775±0.066 respectively). The Bayesian model's robustness studied using a 10 fold cross validation showed a percentage of misclassified subjects of 12.4±1.8%, a sensitivity of 87.7±0.3%, a specificity of 87.5±0.3%, a positive predictive value of 87.8±0.3% and negative predictive value of 87.4±0.2%. As classified by the Bayesian model, the variables most related to successful vaccination were, in descending order: age, eGFR, protidemia, albuminemia, cause of renal failure, gender, previous vaccination and weight. CONCLUSION: The Bayesian network confirmed that both kidney function and nutritional status of patients are important factors to explain the success of vaccination against hepatitis B in CKD patients before dialysis. For research purposes, before an external validation, the network can be used online at www.hed.cc/?s=Bhepatitis&n=ReseauhepatiteBsup10.neta.

Paraplegia as a presentation of primary hyperoxaluria.

30% of the patients suffering from hyperoxaluria type 1 are diagnosed only when they already had reached end-stage renal disease. We report the case of a 57-year-old woman with history of chronic kidney failure presenting with paraplegia due to spinal cord compression by thoracic mass-like lesions. Bone biopsy specimen obtained by decompressive laminectomy revealed calcium oxalate deposits. Once diagnosis of primary hyperoxaluria was confirmed, she underwent haemodialysis with incomplete improvement of her neurological disorders and was registered on the waiting list for transplantation.

[The recommendations of nephrologist are poorly followed by the primary care physician. The example of vaccination against hepatitis B]. / Les recommandations des néphrologues sont peu suivies par les médecins traitants. L'exemple de la vaccination contre l'hépatite B.

The relationship between specialist physician and primary care physician (PCP) has been poorly evaluated in France. We have studied the application of a specialist's recommendation by the PCP. Vaccination against hepatitis B in patients with chronic renal failure was the follow-up marker. After consultation, the nephrologist wrote in his report to the PCP that the vaccination was recommended. At the next nephrological consultation, the patient was asked if the PCP had proposed vaccination. The clinical, biological characteristics and history of the patients were recorded as well as number and location of the PCP consultations. Five nephrology centers recruited 315 patients. In 61.6% (194/315) of the cases, the vaccination was not proposed by the PCP. Only the estimated GFR (lowest in vaccinated patients, 29.5 vs. 34.5mL/min/1.73m2), the delay between the two consultations of the nephrologist (shorter in vaccinated patients, 18.7 vs. 22.9 weeks) and the nephrologist's practice center (17.5 to 52% vaccination rate) are statistically significant in univariate analysis. In multivariate analysis, only the center effect persists. The lack of vaccination was argued by a letter from the PCP in 2 cases (1%). In the absence of a direct questioning of the PCP, the reasons for not following the recommendation remain unexplained. Overall, the recommendation of the nephrologist was little followed. Our study can contribute to the reflection on the shared follow-up of patients suffering from chronic diseases.

[Compliance and leaflet's reading, which link and which media? Results from a French population with chronic kidney disease]. / Observance et lecture des notices, quel lien et quels médias ? Résultats d'une population avec maladie rénale chronique.

Leaflets inside drug boxes are complex and often poorly understood. Patients consulting in nephrology are mostly old and often suffer from multiple comorbidities. As so, they are often subject to various contra-indications and drug interactions. This paper aims to evaluate if patients actually read leaflets or other medical information on others medias such as Internet and whether this could, potentially, interfere with their observance. Results showed that leaflets were read by 65.1% of patients, leading to 12% of withdrawal or not taking drugs. Furthermore, compliance to medical guidance was deemed e-read by 65.1% of patients, leading to 12% of withdrawal or not taken drugs. Furthermore, this study showed no clear profile for non-compliant patients. Even the youngest patients (under 50 years old) have had a good compliance, with not more withdrawal or not taking pills. Nonetheless, youngest patients used more often to consult alternative medias and did not read much of the leaflets' information. Patients who were reading leaflets however, tended to search further information on other medias. This situation would create new challenges in health care, as it seems that data available on new medias are not systematically validated or adapted to the needs of the patients.

Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations?

BACKGROUND: There is an increasing prevalence of diabetes type 2 and chronic kidney disease, challenging appropriate prescribing of oral anti-diabetic drugs (OADs). METHODS: We have described the practice patterns of 13 nephrologists in 4 centers, in a cohort of 301 consecutive adult type 2 diabetic patients. Among oral anti-diabetic prescriptions, we have detailed drugs dosage for each subject, with 3 different formulae for estimating glomerular filtration rate (GFR) and its adequation according to the latest ERBP recommendations (2015). As individuals were mostly obese in this work, we also compare adequacy rates using both standard indexed CKD-EPI formula and CKD-EPI formula de-indexed from body surface area. RESULTS: Using the CKD-EPI formula as the reference method for estimating GFR, 53.5% of patients were outside the recommendations, mostly for metformin (30% of the whole cohort) and for sitagliptin (17.9% of the whole cohort). With Cockcroft and Gault formula, 38.2% of persons were outside recommendations and 45.9% (p<0.001) with CKD-EPI de-indexed. Among individuals consulting a nephrologist for the first time (n=90), 61.1% were outside recommendations (p=0.1). Among those persons under diabetologist supervision (n=103), 63.1% were outside recommendations (p=0.09), and were taking significantly more often metformin and insulin. CONCLUSION: We have found a substantial number of inadequate OAD prescriptions in type 2 diabetic patients with chronic kidney disease. The proportion of individuals outside guidelines was strongly affected by the method used for estimating GFR and by the type of practice, i.e., specialists versus general practitioners.

[Postprandial blood pressure drop in hemodialysis: myth or reality?]. / Collation et chute de pression artérielle en hémodialyse: mythe ou réalité?

The meal is a friendly moment of the sessions of dialysis, appreciated by most of the dialysed persons. However the empirical observation allows to notice that certain dialysed persons, present drops of arterial pressure after taking the meal. Where from the questioning: except factors inherent to the dialysis, has the meal a particular incidence on the blood pressure in the course of session? Numerous studies were realized since 1983 on the low blood pressure comment prandiale at the old person, very few studies are available on the low blood pressure comment prandiale in the course of session of hemodialysis, and sometimes little convincing. A comparative method on 2 sessions, one with meal and one without meal, every patient being its own witness, was used. The tool of evaluation consists of a railing resuming variables retained for the study. In view of the study carried out further to this questioning, the hypothesis of departure does not come true: we cannot demonstrate of significant link between meal and arterial pressure drop. However the number restricted by patients (fifty) include in the study, does not allow us to end in favour of the myth, it is necessary for it to pursue the study to obtain the same data with a much more important population.

Is there a BP benefit of changing the time of aspirin administration in treated hypertensive patients?

BACKGROUND AND DESIGN: The effects of aspirin on blood pressure (BP) are controversial and a chronopharmacological effect of aspirin on 24-hour BP was reported recently in otherwise untreated hypertensive patients. The study was designed to test the timing effect of aspirin dosing on 24-hour BP in treated hypertensive patients routinely taking aspirin for cardiovascular prevention. METHOD AND RESULTS: Seventy-five patients were randomized into two groups. One group was to receive aspirin in the evening then in the morning for 1 month and the other group in the morning then in the evening, following a cross-over design. The principal assessment criterion was 24-hour systolic BP (SBP) measured by 24-hour ambulatory BP monitoring (ABPM). Patients were aged 65 ± 9 years and had been hypertensive for 12 ± 10 years. They were all taking a mean of 2.8 antihypertensive drugs and did not modify their treatment throughout the study. Of the included subjects, 70% were men and 33% were diabetics. Mean 24-hour SBP values were clinically equivalent and were not statistically different, depending on whether the aspirin was taking in the morning or evening (128.3 ± 1.4 vs. 128.3 ± 1.4 mmHg, respectively). Neither was there any significant difference in diurnal and nocturnal SBP or in 24-hour, diurnal, and nocturnal diastolic BP (DBP). CONCLUSION: It does not appear useful to advise patients with long-standing hypertension to modify timing of aspirin intake in order to reduce BP values.

Systolic blood pressure is depending on the arm position when home blood pressure is measured with a wrist or an arm validated monitor.

OBJECTIVES: To compare home blood pressure (BP) values obtained with two validated OMRON (wrist or arm) monitors used in the same individual sequentially, but with two different hand positions. METHODS: In 200 hypertensive individuals referred to hypertension specialists, a self-measurement of BP was performed sequentially with an OMRON M4-I (arm cuff, A/A, British Hypertention Society validation) and an OMRON RX-I (wrist cuff, B/B, BHS validation). Each patient recorded home BP during two periods of 4 days with three measures in the morning and three in the evening. Order for use of each monitor was randomized. For the first 100 patients, the hand was positioned on the opposite shoulder whereas for the next 100 patients, the hand was positioned on the opposite elbow. BP values were reported on a standardized document. RESULTS: In this population, aged 60+/-10 years, with 54% of men, BP values were 136+/-/80+/- mmHg with the wrist monitor (WM) when the hand is positioned on the opposite shoulder as compared with 144+/-16/81+/-9 mmHg obtained with the arm monitor taken as the gold standard. On the contrary, BP values were 142+/-/82+/- mmHg with the WM when the hand is positioned on the opposite elbow as compared with 144+/-16/81+/-9 mmHg obtained with the arm monitor. The lower value of systolic blood pressure observed with WM positioned on the shoulder is independent of age, initial BP level and order of use (multivariate analysis). CONCLUSION: When advising home BP monitoring with a WM, the instruction to be given to patients is to position the hand on the opposite elbow.

[Medical prescriptions in haemodialysis patients: critical analysis]. / Analyse critique des prescriptions médicamenteuses en hémodialyse.

AIM: The aim of the study is to analyse haemodialysis patients' prescriptions accordance with legal registrations in 64 chronic haemodialysis patients during a one-month follow-up period. RESULTS: Patients are taking 9.6+/-3 different drugs. A mean of 2.4+/-1.3 prescriptions per patient disagree with the recommended drug use. The directions for use in this specific population are defective in 89%. Moreover, at least one drug-drug interaction is found in 78% of our patients. CONCLUSION: Only 8% of the studied hemodialysis patients benefit from prescriptions in agreement with the legal recordings, as a consequence of the lack of drug studies in this particular population. Therefore, clinicians have to rely on their own experience to establish their prescriptions, which can involve their responsibility in case of litigation. Furthermore, the frequency of drug-drug interactions in these polymedicated patients implies that a close pharmaceutical follow-up should be implemented.