Considerable international variation exists in blood pressure control and antihypertensive prescription patterns in chronic kidney disease

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes

Regional variation in hemoglobin distribution among individuals with chronic kidney disease: the ISN International Network of Chronic Kidney Disease (iNET-CKD) Cohorts

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin.Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model.Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17–49 ml/min) and 3 pediatric cohorts (median eGFR range of 26–45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7–6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%–44% across cohorts).Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.</p

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

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

Regional Variation in Hemoglobin Distribution Among Individuals With CKD: the ISN International Network of CKD Cohorts

Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin

Evaluation des pratiques cliniques dans la maladie rénale chronique – apport des études observationnelles

Chronic kidney disease (CKD) affects about 10% of the adult population and is associated with high risk of end-stage kidney disease (ESKD), cardiovascular complications, and premature death. Guidelines recommend a number of measures for the prevention of CKD progression and complications, but these recommendations are often based on low evidence or expert opinion. In this thesis, we used observational data to assess clinical practices in two key areas of CKD: arteriovenous (AV) access for hemodialysis, and hypertension control in moderate to severe CKD. Using data from the French REIN registry of renal replacement therapy for ESKD, we showed that only 56% of the 53,092 adult incident patients on hemodialysis from 2005 through 2013 had an AV access (either fistulae or grafts) created at hemodialysis initiation as recommended, of which 16% were nonfunctional, requiring catheter use associated with high mortality risk. Conversion into functional AV access was associated with better outcome, but less than two out of three patients starting hemodialysis with a catheter experienced this conversion within 3 years after dialysis start. In the CKD-REIN cohort study, among 1658 patients with moderate to severe CKD, we found less hypertension control and higher systolic blood pressure to be associated with higher sodium intake assessed from spot urine, but not with lower potassium intake. Spot urinary sodium/potassium ratio did not appear to add value than sodium alone for patient monitoring. Finally, using data from the International Network of Chronic Kidney Disease cohorts (iNET-CKD), including 17 cohort studies over 4 continents (N=34,602 patients with an estimated glomerular filtration rate < 60 mL/min/1.73 m2), we highlighted a global poor hypertension control in CKD with regards to recommendations, with large variations across countries (from 27 to 61% blood pressure ≥140/90 mm Hg). These variations are partly explained by patients’ characteristics, and associated with very different antihypertensive treatment profiles. In conclusion, this thesis points out major gaps between guideline recommendations and CKD management in real life, and provide clues for the prevention of AV access-related complications and better hypertension control.La maladie rénale chronique (MRC) affecte environ 10% de la population adulte et est associée à un risque élevé de progression vers l’insuffisance rénale terminale (IRT), d’événements cardiovasculaires et de décès précoce. Des mesures sont recommandées pour prévenir la progression et les complications de la MRC, mais elles sont souvent basées sur un niveau de preuve faible ou sur la seule opinion d’experts. Dans cette thèse, nous avons utilisé des données observationnelles pour évaluer les pratiques cliniques dans deux domaines clés de la MRC : les abords artérioveineux (AV) en hémodialyse et le contrôle de l’hypertension artérielle (HTA) dans la MRC non terminale. Avec le registre national REIN des traitements de suppléance de l'IRT, nous avons montré que seuls 56% des 53 092 patients adultes incidents en hémodialyse de 2005 à 2013 avaient une voie d’abord AV (fistule ou pontage) créée, telle que recommandée, avant le démarrage de la dialyse, dont 16% étaient non fonctionnelles, nécessitant l'utilisation d'un cathéter associé à une sur-mortalité. La conversion en abord AV fonctionnel était associée à un meilleur pronostic, mais concernait dans les trois premières années de dialyse moins de deux patients sur trois ayant démarré sur cathéter. Dans l’étude de cohorte CKD-REIN, chez 1658 patients avec une MRC modérée à sévère, nous avons mis en évidence un moins bon contrôle de l'HTA et des niveaux de pression artérielle systolique plus élevés en lien avec des apports élevés en sodium, mais pas avec des apports faibles en potassium, évalués sur échantillon urinaire ponctuel. Le ratio sodium/potassium urinaire n'était pas plus discriminant que le sodium seul. Enfin, grâce au réseau International Network of Chronic Kidney Disease cohorts (iNET-CKD), qui inclut 17 cohortes sur 4 continents (N=34 602 patients avec un débit de filtration glomérulaire estimé < 60 mL/min/1,73 m2) nous avons mis en lumière le contrôle médiocre de l’HTA en général dans la MRC au regard des recommandations, avec d'importantes variations entre pays (27 à 61% de pression artérielle ≥140/90 mm Hg) expliquées en partie par les caractéristiques des patients et associées à des profils de traitements antihypertenseurs très différents. En conclusion, cette thèse pointe des écarts importants aux recommandations dans la prise en charge de la MRC en vie réelle et des pistes de prévention des complications liées aux abords AV et un meilleur contrôle de l'HTA

Evaluation of Clinical Practices in Chronique Kidney Disease - Evidence from Observational Studies

La maladie rénale chronique (MRC) affecte environ 10% de la population adulte et est associée à un risque élevé de progression vers l’insuffisance rénale terminale (IRT), d’événements cardiovasculaires et de décès précoce. Des mesures sont recommandées pour prévenir la progression et les complications de la MRC, mais elles sont souvent basées sur un niveau de preuve faible ou sur la seule opinion d’experts. Dans cette thèse, nous avons utilisé des données observationnelles pour évaluer les pratiques cliniques dans deux domaines clés de la MRC : les abords artérioveineux (AV) en hémodialyse et le contrôle de l’hypertension artérielle (HTA) dans la MRC non terminale. Avec le registre national REIN des traitements de suppléance de l'IRT, nous avons montré que seuls 56% des 53 092 patients adultes incidents en hémodialyse de 2005 à 2013 avaient une voie d’abord AV (fistule ou pontage) créée, telle que recommandée, avant le démarrage de la dialyse, dont 16% étaient non fonctionnelles, nécessitant l'utilisation d'un cathéter associé à une sur-mortalité. La conversion en abord AV fonctionnel était associée à un meilleur pronostic, mais concernait dans les trois premières années de dialyse moins de deux patients sur trois ayant démarré sur cathéter. Dans l’étude de cohorte CKD-REIN, chez 1658 patients avec une MRC modérée à sévère, nous avons mis en évidence un moins bon contrôle de l'HTA et des niveaux de pression artérielle systolique plus élevés en lien avec des apports élevés en sodium, mais pas avec des apports faibles en potassium, évalués sur échantillon urinaire ponctuel. Le ratio sodium/potassium urinaire n'était pas plus discriminant que le sodium seul. Enfin, grâce au réseau International Network of Chronic Kidney Disease cohorts (iNET-CKD), qui inclut 17 cohortes sur 4 continents (N=34 602 patients avec un débit de filtration glomérulaire estimé < 60 mL/min/1,73 m2) nous avons mis en lumière le contrôle médiocre de l’HTA en général dans la MRC au regard des recommandations, avec d'importantes variations entre pays (27 à 61% de pression artérielle ≥140/90 mm Hg) expliquées en partie par les caractéristiques des patients et associées à des profils de traitements antihypertenseurs très différents. En conclusion, cette thèse pointe des écarts importants aux recommandations dans la prise en charge de la MRC en vie réelle et des pistes de prévention des complications liées aux abords AV et un meilleur contrôle de l'HTA.Chronic kidney disease (CKD) affects about 10% of the adult population and is associated with high risk of end-stage kidney disease (ESKD), cardiovascular complications, and premature death. Guidelines recommend a number of measures for the prevention of CKD progression and complications, but these recommendations are often based on low evidence or expert opinion. In this thesis, we used observational data to assess clinical practices in two key areas of CKD: arteriovenous (AV) access for hemodialysis, and hypertension control in moderate to severe CKD. Using data from the French REIN registry of renal replacement therapy for ESKD, we showed that only 56% of the 53,092 adult incident patients on hemodialysis from 2005 through 2013 had an AV access (either fistulae or grafts) created at hemodialysis initiation as recommended, of which 16% were nonfunctional, requiring catheter use associated with high mortality risk. Conversion into functional AV access was associated with better outcome, but less than two out of three patients starting hemodialysis with a catheter experienced this conversion within 3 years after dialysis start. In the CKD-REIN cohort study, among 1658 patients with moderate to severe CKD, we found less hypertension control and higher systolic blood pressure to be associated with higher sodium intake assessed from spot urine, but not with lower potassium intake. Spot urinary sodium/potassium ratio did not appear to add value than sodium alone for patient monitoring. Finally, using data from the International Network of Chronic Kidney Disease cohorts (iNET-CKD), including 17 cohort studies over 4 continents (N=34,602 patients with an estimated glomerular filtration rate < 60 mL/min/1.73 m2), we highlighted a global poor hypertension control in CKD with regards to recommendations, with large variations across countries (from 27 to 61% blood pressure ≥140/90 mm Hg). These variations are partly explained by patients’ characteristics, and associated with very different antihypertensive treatment profiles. In conclusion, this thesis points out major gaps between guideline recommendations and CKD management in real life, and provide clues for the prevention of AV access-related complications and better hypertension control

Prevalência e fatores associados à doença renal crônica em pacientes internados em um hospital universitário na cidade de São Paulo, SP, Brasil

Introdução: A doença renal crônica (DRC) constitui importante problema de saúde pública mundial. Contudo, dados sobre prevalência e comorbidades são escassos no Brasil. Objetivo: Identificar a prevalência e fatores associados à DRC em pacientes internados em um hospital universitário. Métodos: Foram selecionados, aleatoriamente, 826 prontuários de pacientes internados em clínica médica. A DRC foi baseada no diagnóstico médico descrito no prontuário. Foram coletadas informações clínico-demográficas e feitas comparações entre pacientes com e sem DRC. Resultados: A prevalência de DRC foi 12,7%. Os pacientes com DRC se distinguiram daqueles sem a doença (p < 0,05) por terem companheiro (59,8% vs. 47,3%); idade mais elevada (65,8 ± 15,6 vs. 55,3 ± 18,9 anos); mais comorbidades como hipertensão arterial (75,2% vs. 46,3%), diabetes (49,5% vs. 22,4%), dislipidemia (23,8% vs. 14,9%), infarto do miocárdio (14,3% vs. 6,0%) e insuficiência cardíaca congestiva (18,1% vs. 4,3%); maior período de internação (11 (8-18) vs. 9 (6-12) dias) e; mais óbitos (12,4% vs. 1,4%). A análise de regressão logística indicou associação independente (OR, odds ratio; IC, intervalo de confiança de 95%) da DRC com idade (OR 1,019, IC 1,003-1,036), hipertensão arterial (OR 2,032, IC 1,128-3,660), diabetes (OR 2,097, IC 1,232-3,570) e insuficiência cardíaca congestiva (OR 2,665, IC 1,173-6,056). Conclusão: A prevalência de DRC em pacientes internados em clínica médica foi alta, sendo estes pacientes clinicamente mais complexos, visto apresentarem idade mais elevada e maior número de comorbidades, refletindo em maior risco de óbito durante internação hospitalar

CARDIOVASCULAR IMPACT OF DISCONTINUATION OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN ADVANCED CHRONIC KIDNEY DISEASE

International audienceObjective: Hypertension is a major problem in chronic kidney disease (CKD) with a prevalence approaching 100%, contributing to the risk of CKD progression, cardiovascular events and all-cause mortality. Renin-angiotensin system inhibitors (RASi) are the first-line therapy for antihypertensive treatment in patients with CKD, due to its protective effects. However, it is common practice stopping RASi in advanced CKD to attempt to delay kidney replacement therapy (KRT) initiation and/or to prevent drug-related acute kidney injury. Design and method: From the CKD-Rein prospective cohort, which included 3033 outpatients from nephrology clinics in France, we selected participants with an estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73m2 and who were treated with RASi for at least 3 months. We used the G-formula to deal with time-fixed (age, sex, diabetes, heart failure, lung diseases) and time-varying confounding (eGFR, systolic blood pressure, serum sodium and potassium, diuretic prescription) to compare two treatment strategies: to discontinue or to continue RASi. The outcome, MACE, was the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure. Competing risks were initiation of KRT and non-cardiovascular death. Results: From the 1,472 patients included (median age 69 years, median eGFR 25mL/min/1.73m2, 34% women), 27% discontinued RASi over a median follow-up of 35 [17-51] months. The crude rate of RASi discontinuation was higher in the presence of cardiovascular comorbidities and more severe CKD. The number of reported serious adverse reactions over the follow-up (such as acute kidney injury or hyperkalemia) was low, but higher in the discontinuation than in the continuation group (47 versus 23 per 1,000 person-years). After taking the afore-mentioned potential confounders into account, the 36-month risk of MACE was twice as high in the discontinuation group as that in the continuation group (RR 2.13, 95%CI 1.60-2.85). Conclusions: RASi discontinuation was significantly associated with MACE risk, the leading cause of morbidity and mortality in advanced CKD. Our results, along with other published data, suggest that the risk-benefit balance favors continued use of RASi in this population

Arteriovenous Access and Outcomes in Incident Hemodialysis Patients: Is Fistula First Approach Still Holding?

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 <10%) within the overall population and the subgroups of interest (except for the timing of AV access creation in patients aged <70). Over a median follow-up of 48 months (IQR 27–48), hospitalization rates were 334 and 310 per 100 patient-years in the AV graft and fistula groups, respectively; mortality rates were 16 and 13 per 100 patient-years. Patients with AV graft had a 14% higher hazard of all-cause hospitalization (HR 1.14, 95% CI 1.08–1.20), which was only slightly attenuated in IPW analysis (wHR 1.11, 1.09–1.13). AV access type was not associated with mortality—HR 1.03 (0.89–1.19), wHR 1.11 (0.85–1.46). Results were consistent for most subgroups, except that the highest hazard of hospitalization with AV grafts compared to fistulæ was much attenuated in patients with diabetes, heart failure or peripheral artery disease with respect to patients without these comorbidities (Figure 1). 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