Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Dialysis Patients’ Preferences on Resuscitation: A Cross-Sectional Study Design

Background: End-stage kidney disease is associated with a 10- to 100-fold increase in cardiovascular mortality compared with age-, sex-, and race-matched population. Cardiopulmonary resuscitation (CPR) in this cohort has poor outcomes and leads to increased functional morbidity. Objective: The aim of this study is to assess patients’ preferences toward CPR and advance care planning (ACP). Design: cross-sectional study design. Setting: Two outpatient dialysis units. Patients: Adults undergoing dialysis for more than 3 months were included. Exclusion criteria were severe cognitive impairment or non-English-speaking patients. Measurements: A structured interview with the use of Willingness to Accept Life-Sustaining Treatment (WALT) tool. Methods: Demographic data were collected, and baseline Montreal Cognitive Assessment, Patient Health Questionnaire–9, Duke Activity Status Index, Charlson comorbidity index, and WALT instruments were used. Descriptive analysis, chi-square, and t test were performed along with probability plot for testing hypotheses. Results: Seventy participants were included in this analysis representing a 62.5% response rate. There was a clear association between treatment burden, anticipated clinical outcome, and the likelihood of that outcome with patient preferences. Low-burden treatment with expected return to baseline was associated with 98.5% willingness to accept treatment, whereas high-burden treatment with expected return to baseline was associated with 94.2% willingness. When the outcome was severe functional or cognitive impairment, then 45.7% and 28.5% would accept low-burden treatment, respectively. The response changed based on the likelihood of the outcome. In terms of resuscitation, more than 75% of the participants would be in favor of receiving CPR and mechanical ventilation at their current health state. Over 94% of patients stated they had never discussed ACP, whereas 59.4% expressed their wish to discuss this with their primary nephrologist. Limitations: Limited generalizability due to lack of diversity. Unclear decision stability due to changes in health status and patients’ priorities. Conclusions: ACP should be incorporated in managing chronic kidney disease (CKD) to improve communication and encourage patient involvement

Acute interstitial nephritis with podocyte foot-process effacement complicating Plasmodium falciparum infection

Abstract Background Malarial acute renal failure (MARF) is a component of the severe malaria syndrome, and complicates 1–5% of malaria infections. This form of renal failure has not been well characterized by histopathology. Case presentation A 44 year-old male presented to the emergency department with a 5-day history of fever and malaise after returning from Nigeria. A blood film was positive for Plasmodium falciparum. His creatinine was 616 µmol/L coming from a normal baseline of 89 µmol/L. He had a urine protein:creatinine ratio of 346 mg/mmol (4.4 g/L). He required dialysis. A renal biopsy showed acute interstitial nephritis with podocyte foot-process effacement. He was treated with artesunate and his renal function improved. At 1 year follow-up his creatinine had plateaued at 120 µmol/L with persistent low-grade proteinuria. Conclusion Acute interstitial nephritis and podocyte foot-process effacement might be under-recognized lesions in MARF. Studying the mechanisms of MARF could give insight into the immunopathology of severe malaria

The impact of renal insufficiency and anaemia on survival in patients with cardiovascular disease: a cohort study

Background: The simultaneous occurrence of cardiovascular disease (CVD), kidney disease, and anaemia is associated with increased morbidity and mortality. In the community setting, little data exists about the risk associated with milder levels of anaemia when it is present concurrently with CVD and chronic kidney disease (CKD). The aim of this study was to establish the prevalence of CKD and anaemia in patients with CVD in the community and to examine whether the presence of anaemia was associated with increased morbidity and mortality. Methods: This study was designed as a retrospective cohort study and involved a random sample of 35 general practices in the West of Ireland. A practice-based sample of 1,609 patients with established cardiovascular disease was generated in 2000/2001 and followed for five years. The primary endpoint was death from any cause. Statistical analysis involved using one-way ANOVA and Chi-squared tests for baseline data and Cox proportional-hazards models for mortality data. Results: Of the study sample of 617 patients with blood results, 33% (n = 203) had CKD while 6% (n = 37) had CKD and anaemia. The estimated risk of death from any cause, when compared to patients with cardiovascular disease only, was almost double (HR = 1.98, 95% CI 0.99 to 3.98) for patients with both CVD and CKD and was over 4 times greater (HR = 4.33, 95% CI 1.76 to 10.68) for patients with CVD, CKD and anaemia. Conclusion: In patients with cardiovascular disease in the community, chronic kidney disease and anaemia occur commonly. The presence of chronic kidney disease carries an increased mortality risk which increases in an additive way with the addition of anaemia. These results suggest that early primary care diagnosis and management of this high risk group may be worthwhile

The impact of renal insufficiency and anaemia on survival in patients with cardiovascular disease: a cohort study

Background: The simultaneous occurrence of cardiovascular disease (CVD), kidney disease, and anaemia is associated with increased morbidity and mortality. In the community setting, little data exists about the risk associated with milder levels of anaemia when it is present concurrently with CVD and chronic kidney disease (CKD). The aim of this study was to establish the prevalence of CKD and anaemia in patients with CVD in the community and to examine whether the presence of anaemia was associated with increased morbidity and mortality. Methods: This study was designed as a retrospective cohort study and involved a random sample of 35 general practices in the West of Ireland. A practice-based sample of 1,609 patients with established cardiovascular disease was generated in 2000/2001 and followed for five years. The primary endpoint was death from any cause. Statistical analysis involved using one-way ANOVA and Chi-squared tests for baseline data and Cox proportional-hazards models for mortality data. Results: Of the study sample of 617 patients with blood results, 33% (n = 203) had CKD while 6% (n = 37) had CKD and anaemia. The estimated risk of death from any cause, when compared to patients with cardiovascular disease only, was almost double (HR = 1.98, 95% CI 0.99 to 3.98) for patients with both CVD and CKD and was over 4 times greater (HR = 4.33, 95% CI 1.76 to 10.68) for patients with CVD, CKD and anaemia. Conclusion: In patients with cardiovascular disease in the community, chronic kidney disease and anaemia occur commonly. The presence of chronic kidney disease carries an increased mortality risk which increases in an additive way with the addition of anaemia. These results suggest that early primary care diagnosis and management of this high risk group may be worthwhile.PUBLISHEDpeer-reviewe

Multimorbidity and risk among patients with established cardiovascular disease: a cohort study

Background Most patients managed in primary care have more than one condition. Multimorbidity presents challenges for the patient and the clinician, not only in terms of the process of care, but also in terms of management and risk assessment. Aim To examine the effect of the presence of chronic kidney disease and diabetes on mortality and morbidity among patients with established cardiovascular disease. Design of study Retrospective cohort study. Setting Random selection of 35 general practices in the west of Ireland. Method A practice-based sample of 1609 patients with established cardiovascular disease was generated in 2000-2001 and followed for 5 years. The primary endpoint was death from any cause and the secondary endpoint was a cardiovascular composite endpoint that included death from a cardiovascular cause or any of the following cardiovascular events: myocardial infarction, heart failure, peripheral vascular disease, or stroke. Results Risk of death from any cause was significantly increased in patients with increased multimorbidity (P&amp;lt;0.001), as was the risk of the cardiovascular composite endpoint (P&amp;lt;0.001). Patients with cardiovascular disease and diabetes had a similar survival pattern to those with cardiovascular disease and chronic kidney disease, but experienced more cardiovascular events. Conclusion Level of multimorbidity is an independent predictor of prognosis among patients with established cardiovascular disease. In such patients, the presence of chronic kidney disease carries a similar mortality risk to diabetes. Multimorbidity may be a useful factor in prioritising management of patients in the community with significant cardiovascular risk

Sodium intake and renal outcomes: a systematic review

BACKGROUND Sodium intake is an important determinant of blood pressure; therefore, reduction of intake may be an attractive population-based target for chronic kidney disease (CKD) prevention. Most guidelines recommend sodium intake of &amp;lt;2.3 g/day, based on limited evidence. We reviewed the association between sodium intake and renal outcomes. METHODS We reviewed cohort studies and clinical trials, which were retrieved by searching electronic databases, that evaluated the association between sodium intake/excretion and measures of renal function, proteinuria, or new need for dialysis. RESULTS Of 4,337 reviewed citations, seven (n = 8,129) were eligible, including six cohort studies (n = 7,942) and one clinical trial (n = 187). Four studies (n = 1,787) included patients with CKD. All four cohort studies reported that high intake (&amp;gt;4.6 g/day) was associated with adverse outcomes (vs. moderate/low), while none reported an increased risk with moderate intake (vs. low). Three studies (n = 6,342) included patients without CKD. Two cohort studies (n = 6,155) reported opposing directions of association between low (vs. moderate) sodium intake and renal outcomes, and one clinical trial (n = 187) reported a benefit from low intake (vs. moderate) on proteinuria but an adverse effect on serum creatinine. CONCLUSIONS Available, but limited, evidence supports an association between high sodium intake (&amp;gt;4.6 g/day) and adverse outcomes. However, the association with low intake (vs. moderate) is uncertain, with inconsistent findings from cohort studies. There is urgent need to clarify the long-term efficacy and safety of currently recommended low sodium intake in patients with CKD