Cardiorenal syndrome and the association with fitness: Data from a telerehabilitation randomized clinical trial.

AIMS: To investigate the associations of cardiorespiratory fitness with cardiac, vascular, renal and cardiorenal characteristics in chronic heart failure in a telerehabilitation randomized clinical trial. Secondly, to evaluate the associations of cardiorenal syndrome with the effects of exercise. METHODS AND RESULTS: Sixty-nine heart failure patients attended baseline examination, and 61 patients were randomly assigned 1:1 to 3-month telerehabilitation or control. Data were collected at baseline and 3-month post-intervention, including echocardiography and vascular ultrasound, laboratory tests, exercise test with peak oxygen consumption (VO2peak ) measurement and 6-min walk test (6MWT). Baseline VO2peak and 6MWT distance was 0.85 mL*min-1 *kg-1 lower and 20 m shorter per 10 mL/min/1.73m2 lower estimated glomerular filtration rate (both P < 0.001). Heart failure patients with cardiorenal syndrome had 3.5 (1.1) mL*min-1 *kg-1 lower VO2peak and diastolic dysfunction grade 2-3, and elevated filling pressure was >50% more common compared with those without (all P < 0.05). At the 3-month post-intervention follow-up, only the non-CRS patients in the intervention group increased VO2peak (0.73 (0.51) mL*min-1 *kg-1 ), whereas VO2peak in the CRS subpopulation of controls decreased (-1.34 (0.43) mL*min-1 *kg-1 ). Cardiorenal syndrome was associated with a decrease in VO2peak in CRS patients compared with non-CRS patients, -0.91 (0.31) vs. 0.39 (0.35) mL*min-1 *kg-1 respectively, P = 0.013. CONCLUSIONS: Cardiorenal syndrome was negatively associated with VO2peak and 6MWT distance in chronic HF, and the associations were stronger than for heart failure phenotypes and other characteristics. The effect of exercise was negatively associated with cardiorenal syndrome. Exercise seems to be as important in heart failure patients with cardiorenal syndrome, and future studies should include CRS patients to reveal the most beneficial type of exercise.

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model.

There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75-0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved.

The conundrum of chronic kidney disease classification and end-stage renal risk prediction in the elderly--what is the right approach?

The worldwide high prevalence of chronic kidney disease (CKD) and the increasing number of patients reaching end-stage renal disease (ESRD) are a matter of major concern. The most widely accepted classification system of CKD is that proposed by the Kidney Disease Outcomes Quality Initiative (KDOQI) in 2002. When applying this system, it has become apparent that the prevalence of CKD is particularly high in elderly subjects. The fact that this system is mainly based on estimated glomerular filtration rate (eGFR), subdividing the severity of CKD into five stages, is a matter of debate. A main issue is that although a reduced eGFR is often encountered in elderly subjects, most of these subjects do not have a renal disease leading to an increased risk of ESRD, i.e. the predictive power of ESRD is unsatisfactory. Recent advances have been put forward to improve (1) estimation of GFR and (2) prediction of ESRD. In this review, we discuss the currently available data with a focus on the elderly and propose an improved classification system of CKD which is characterized by a substantially better diagnostic accuracy for progression to ESRD. This is simply and cost-effectively accomplished by subdividing stage 3 CKD into two groups (eGFR 30-44 and 45-59 ml/min/1.73 m(2)) and by complementing all levels of eGFR with information about urinary albumin excretion, i.e. whether normoalbuminuria, microalbuminuria, or macroalbuminuria is present. The consequence should be a revision of the 2002 KDOQI CKD classification system according to these findings, which would be a significant step forward, particularly for elderly CKD patients.

Use of a prostate symptom score to identify men at risk of future kidney failure: insights from the HUNT II Study.

BACKGROUND: Chronic kidney disease (CKD) screening beyond patients with diabetes mellitus or hypertension increasingly is discussed. Some guidelines recommend kidney function testing of patients with benign prostatic hyperplasia; however, the significance of extending this to general population screening is unclear. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 30,466 men from the HUNT II (Second Health Study in Nord-Trøndelag; 1995-1997) representing 66.8% of the entire adult male population in Nord-Trøndelag County, Norway. PREDICTOR: The International Prostate Symptom Score was used to detect the presence and severity of lower urinary tract symptoms (LUTS), a surrogate measure of benign prostate hyperplasia suitable for use in general practice. OUTCOMES: Kidney failure was defined as starting renal replacement therapy or CKD death with a documented stable estimated glomerular filtration rate<15 mL/min/1.73 m2. RESULTS: During 10.5 years of follow-up, 78 men developed kidney failure. Kidney failure risks were 2.60 (95% CI, 1.47-4.58) and 4.08 (95% CI, 1.74-9.53) times higher for men with moderate and severe LUTS compared with men with no/mild LUTS, respectively. However, age-stratified analysis showed that the incidence rate ratio for moderate/severe LUTS versus no/mild LUTS was 1.27 (95% CI, 0.76-2.13), and multivariable Cox analysis showed no significant association between LUTS and risk of kidney failure. Screening effectiveness was improved only slightly by including men with moderate/severe LUTS in addition to patients with diabetes, hypertension, or cardiovascular disease. Better effectiveness was achieved by simply including all men older than 60 years. LIMITATIONS: The ability of the International Prostate Symptom Score to predict the presence and severity of obstruction is only moderate. Ascertainment of severe CKD (estimated glomerular filtration rate, 30-15 mL/min/1.73 m2) was not possible. CONCLUSION: LUTS were not significantly associated with future kidney failure after adjusting for age and therefore in isolation are not a basis for kidney failure screening.

Relationship between chronic kidney disease prevalence and end-stage renal disease risk.

PURPOSE OF REVIEW: Incidence of end-stage renal disease has increased dramatically during the last 30 years and screening for early stages of chronic kidney disease is often suggested as a preventive measure. The relationship between chronic kidney disease and end-stage renal disease is complex, however, and recent studies have given some insights into this relationship. The review will summarize these studies and briefly discuss the clinical implications. RECENT FINDINGS: While the prevalence of chronic kidney disease is high in most Western countries, the incidence of end-stage renal disease differs substantially. The general increase in the incidence of end-stage renal disease seen in recent years may be partially explained by a lower cardiovascular mortality, allowing more patients with chronic kidney disease to develop end-stage renal disease, and widening of entrance criteria for renal replacement therapy. Data do not, however, support these factors as explanatory for the existing international differences. These differences are better explained by different prevalences of diabetes and obesity as well as by differences in rate of progression from early chronic kidney disease stages to end-stage renal disease. Rate of progression seems to be affected by race, socioeconomic status and predialytic care. SUMMARY: Several mechanisms influence the relationship between chronic kidney disease and risk of end-stage renal disease. Decreased cardiovascular mortality and improved treatment availability may explain parts of the increase in the incidence of end-stage renal disease, and there are also large international differences in rates of progression from chronic kidney disease to end-stage renal disease that may be amendable by public health and predialytic care interventions.