Sex and the Risk of Atheromatous and Non-Atheromatous Cardiovascular Disease in CKD: Findings From the CKD-REIN Cohort Study.

RATIONALE & OBJECTIVE: Sex differences in cardiovascular disease (CVD) are well-established, but whether chronic kidney disease (CKD) modifies these risk differences, and whether they differ between atheromatous (ACVD) and non-atheromatous (N-ACVD) CVD is unknown. Assessing this interaction was the principal goal of this study. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adults enrolled in the CKD-Renal Epidemiology and Information Network (CKD-REIN) cohort from from 2013 to 2020, a nationally representative sample of 40 nephrology clinics in France. EXPOSURE: Sex. OUTCOMES: Fatal and non-fatal composite ACVD events (ischaemic coronary, cerebral, and peripheral artery disease) and composite N-ACVD events (heart failure, haemorrhagic stroke, and arrhythmias). ANALYTICAL APPROACH: Multivariable cause-specific Cox proportional hazards models. RESULTS: 1,044 women and 1,976 men with moderate to severe CKD (median age, 67 vs. 69; mean estimated glomerular filtration rate [eGFR], 32±12 vs. 33±12 mL/min/1.73m2) were studied. Over a median follow-up of 5.0 (interquartile range, 4.8;5.2) years, the ACVD rate (per 100 patient-years) was significantly lower in women than men: 2.1 (95% confidence interval: 1.6-2.5) vs 3.6 (3.2-4.0) (P<0.01), while the N-ACVD rate was not: 5.7 (5.0-6.5) vs 6.4 (5.8-7.0) (P=0.55). N-ACVD had a steeper relationship with eGFR than did ACVD. There was an interaction (P<0.01) between sex and baseline eGFR and the ACVD hazard: the adjusted hazard ratio for women compared to men was 0.42 (0.25;0.71) at 45 mL/min/1.73m2 and gradually attenuated at lower levels of eGFR, reaching 1.00 (0.62;1.63) at 16 mL/min/1.73m2. In contrast, the N-ACVD hazard did not differ between the sexes across the eGFR range studied. LIMITATIONS: Cardiovascular biomarkers and sex hormones were not assessed. CONCLUSION: This study shows how the lower risk of ACVD among women compared to men attenuates fully with kidney disease progression. The equal risk of N-ACVD between sexes across CKD stages and its steeper association with eGFR suggest an important contribution of CKD to the development of this CVD type.

Prevalence and factors associated with masked hypertension in chronic kidney disease.

OBJECTIVES: Optimal blood pressure (BP) control is key to prevent cardiovascular complications in patients with chronic kidney disease (CKD). We described the prevalence and factors associated with masked hypertension in CKD. METHODS: We analyzed 1113 ambulatory 24-h BP monitoring (ABPM) records of 632 patients referred for kidney function evaluation. Masked hypertension was defined as office BP less than 140/90 mmHg but daytime BP at least 135/85 mmHg or nighttime BP at least 120/70 mmHg. Factors associated with masked hypertension were assessed with mixed logistic regression models. RESULTS: At inclusion, 424 patients (67%) had controlled office BP, of whom 56% had masked hypertension. In multivariable analysis conducted in all visits with controlled office BP ( n  = 782), masked hypertension was positively associated with male sex [adjusted OR (95% confidence interval) 1.91 (1.16-3.27)], sub-Saharan African origin [2.51 (1.32-4.63)], BMI [1.11 (1.01-1.17) per 1 kg/m 2 ], and albuminuria [1.29 [1.12 - 1.47] per 1 log unit), and was negatively associated with plasma potassium (0.42 [0.29 - 0.71] per 1 mmol/L) and 24-h urinary potassium excretion (0.91 [0.82 - 0.99] per 10 mmol/24 h) as well as the use of renin-angiotensin-aldosterone (RAAS) blockers (0.56 [0.31 - 0.97]) and diuretics (0.41 [0.27 - 0.72]). CONCLUSION: Our findings support the routine use of ABPM in CKD, as more than half of the patients with controlled office BP had masked hypertension. Weight control, higher potassium intake (with caution in advanced CKD), correction of hypokalemia, and larger use of diuretics and RAAS blockers could be potential levers for better out-of-office BP control.

Conservative Kidney Management Practice Patterns and Resources in the United States: A Cross-Sectional Analysis of CKDopps (Chronic Kidney Disease Outcomes and Practice Patterns Study) Data.

Rationale & Objective: Conservative kidney management (CKM) is a viable treatment option for many patients with chronic kidney disease. However, CKM practices and resources in the United States are not well described. We undertook this study to gain a better understanding of factors influencing uptake of CKM by describing: (1) characteristics of patients who choose CKM, (2) provider practice patterns relevant to CKM, and (3) CKM resources available to providers. Study Design: Cross-sectional study. Setting & Participants: This study is a cross-sectional analysis of data from US nephrology clinics enrolled in the chronic kidney disease Outcomes and Practice Patterns Study (CKDopps) collected between 2014 and 2020. Data for this study includes chart-abstracted characteristics of patients with an estimated glomerular filtration rate ≤30mL/min/1.73m2 (n=1018) and available information on whether a decision had been made to pursue CKM at the time of kidney failure, patient (n=407) reports of discussions about forgoing dialysis, and provider (n=26) responses about CKM delivery and available resources in their health systems. Analytical Approach: Descriptive statistics were used to report patient demographics, clinical information, provider demographics, and clinic characteristics. Results: Among data from 1018 patients, 68 (7%) were recorded as planning for CKM. These patients were older, had more comorbidities, and were more likely to require assistance with transfers. Of the 407 patient surveys, 18% reported a conversation about forgoing dialysis with their nephrologist. A majority of providers felt comfortable discussing CKM; however, no clinics had a dedicated clinic or protocol for CKM. Limitations: Inconsistent survey terminology and unlinked patient and provider responses. Conclusions: Few patients reported discussion of forgoing dialysis with their providers and even fewer anticipated a choice of CKM on reaching kidney failure. Most providers were comfortable discussing CKM, but practiced in clinics that lacked dedicated resources. Further research is needed to improve the implementation of a CKM pathway. Plain-Language Summary: For older comorbid adults with kidney failure, conservative kidney management (CKM) can be an appropriate treatment choice. CKM is a holistic approach with treatment goals of maximizing quality of life and preventing progression of chronic kidney disease (CKD) without initiation of dialysis. We investigated US CKM practices and found that among 1018 people with CKD, only 7% were planning for CKM. Of 407 surveyed patients, 18% reported a conversation with their provider about forgoing dialysis. In contrast, most providers felt comfortable discussing CKM; however, none reported working in an environment with a dedicated CKM clinic or protocol. Our data show the need for further CKM education in the United States as well as dedicated resources for its delivery.

A New Approach for Cognitive Impairment Pattern in Chronic Kidney Disease.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is associated with an elevated risk of neurocognitive disorders (NCDs). It remains unclear whether CKD-related NCDs have specific cognitive pattern or are earlier-onset phenotypes of the main NCDs (vascular NCDs and Alzheimer's disease). METHODS: We used the Mini Mental State Examination score (MMSE) to assess cognitive pattern in 3003 CKD patients (stage 3 to 4) followed up over 5 years in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort. After normalizing MMSE scores to a 0-to-100 scale, the associations between the baseline estimated glomerular filtration rate (eGFR, using the CKD-EPI-creatinine formula) and changes in each MMSE domain score were assessed in linear mixed models. RESULTS: Patients (age: 67±13 years old; males: 65%, mean eGFR: 33±12 ml/min/1.73 m²) had a good baseline cognitive functions: the mean MMSE score was 26.9/30 ±2.9. After adjustment for age, sex, educational level, depression (past or present), cardiovascular risk factors, cerebrovascular disease, a lower baseline eGFR (per 10 ml/min/1.73 m²) was associated with a 0.53-point decrement (p<0.001; 95%CI [-0.98,-0.08]) for orientation, a 1.04-point decrement (p=0.03; 95%CI [-1.96,-0.13]) for attention and calculation, a 0.78-point decrement (p=0.003; 95%CI [-1.30,-0.27]) for language, and a 0.94-point decrement (p=0.02; 95%CI [-1.75,-0.13]) for praxis. Baseline eGFR was not, however, associated with significant changes over time in MMSE domain scores. CONCLUSION: A lower eGFR in CKD patients was associated with early impairments in certain cognitive domains: praxis, language and attention domains before an obvious cognitive decline. Early detection of NCD in CKD patients must be perform before clinically cognitive decline using preferably tests assessing executive, attentional functions and language than memory test. This could lead to a better management of cognitive impairment and their consequences on CKD management.

Urgent-start dialysis in patients referred early to a nephrologist-the CKD-REIN prospective cohort study.

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 <48 hours after presentation to correct life-threatening manifestations' according to the Kidney Disease: Improving Global Outcomes 2018 definition. 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.