Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease.

OBJECTIVE: Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease. APPROACH AND RESULTS: We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m(2) and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.8±4.4 mL/min/1.73 m(2)/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (-0.1 mL/min/1.73 m(2)/y; 95% confidence interval, -0.7 to 0.5; P=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m(2) (hazard ratio, 1.54; 95% confidence interval, 1.13-2.10; P=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20-2.59; P=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline. CONCLUSIONS: In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study.

Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation.

BACKGROUND: Physical activity (PA) and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR) meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self-efficacy as barriers to PA in RTR. METHODS: RTR were investigated between 2001-2003. The Tampa Score of Kinesiophobia-Dutch Version (TSK-11) was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). RESULTS: A total of 487 RTR (age 51±12 years, 55% men) were studied. Median score [interquartile range] on TSK-11 was 22 [17-26]. Low physical self-efficacy (Exp B:0.41[0.31-0.54], p<0.001) and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03-1.63],p = 0.03) were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73%) of the effect of fear of movement on PA was explained by low physical self-efficacy. CONCLUSIONS: This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation.

Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression.

Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by the level of albuminuria. Therefore, research focuses on discovering and validating additional biomarkers that improve risk stratification for future renal function decline and end-stage renal disease in patients with diabetes, on top of established biomarkers. Most studies address the value of single biomarkers to predict progressive renal disease and aim to understand the mechanisms that underlie accelerated renal function decline. Since diabetic kidney disease is a disease encompassing several pathophysiological processes, a combination of biomarkers may be more likely to improve risk prediction than a single biomarker. In this review, we provide an overview of studies on the use of multiple biomarkers and biomarker panels, appraise their study design, discuss methodological pitfalls and make recommendations for future biomarker panel studies.

Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.

INTRODUCTION: The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone. AREAS COVERED: This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of finerenone. EXPERT OPINION: The selectivity and greater binding affinity of finerenone to the MR may reduce the risk of hyperkalemia and renal dysfunction and thereby overcome the reluctance to start and uptitrate MRAs in patients with HF and diabetic kidney disease. Studies conducted in patients with HFrEF and moderate chronic kidney disease and diabetic kidney disease, showed promising results. Phase III trials will have to show whether finerenone might become the third-generation MRA for the treatment of HF and diabetic kidney disease.

Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).

BACKGROUND: Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. STUDY DESIGN: Post hoc analysis of 2 multicenter randomized controlled trials. SETTING & PARTICIPANTS: 2,628 adults with type 2 diabetes and nephropathy. FACTOR: Serum bicarbonate level. OUTCOMES: Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. MEASUREMENTS: Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. RESULTS: Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. LIMITATIONS: Post hoc analysis and single measurement of serum bicarbonate. CONCLUSIONS: In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations.