Accelerometer-measured physical activity and functional behaviours among people on dialysis.

BACKGROUND: The feasibility of wrist-worn accelerometers, and the patterns and determinants of physical activity, among people on dialysis are uncertain. METHODS: People on maintenance dialysis were fitted with a wrist-worn AxivityAX3 accelerometer. Subsets also wore a 14-day electrocardiograph patch (Zio®PatchXT) and wearable cameras. Age-, sex- and season-matched UK Biobank control groups were derived for comparison. RESULTS: Median (interquartile range) accelerometer wear time for the 101 recruits was 12.5 (10.4-13.5) days, of which 73 participants (mean age 66.5 years) had excellent wear on both dialysis and non-dialysis days. Mean (standard error) overall physical activity levels were 15.5 (0.7) milligravity units (mg), 14.8 (0.7) mg on dialysis days versus 16.2 (0.8) mg on non-dialysis days. This compared with 28.1 (0.5) mg for apparently healthy controls, 23.4 (0.4) mg for controls with prior cardiovascular disease (CVD) and/or diabetes mellitus and 22.9 (0.6) mg for heart failure controls. Each day, we estimated that those on dialysis spent an average of about 1 hour (h/day) walking, 0.6 h/day engaging in moderate-intensity activity, 0.7 h/day on light tasks, 13.2 h/day sedentary and 8.6 h/day asleep. Older age and self-reported leg weakness were associated with decreased levels of physical activity, but the presence of prior CVD, arrhythmias and listing for transplantation were not. CONCLUSIONS: Wrist-worn accelerometers are an acceptable and reliable method to measure physical activity in people on dialysis and may also be used to estimate functional behaviours. Among people on dialysis, who are broadly half as active as general population controls, age and leg weakness appear to be more important determinants of low activity levels than CVD.

Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease.

BACKGROUND: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate to severe chronic kidney disease are unknown. METHODS: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m2 who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual's baseline measured GFR. All analyses were by intention to treat. RESULTS: In total, 207 participants were assigned to sacubitril/valsartan and 207 to irbesartan. Baseline measured GFR was 34.0 (SE, 0.8) and 34.7 (SE, 0.8) mL/min/1.73 m2, respectively. At 12 months, there was no difference in measured GFR: 29.8 (SE 0.5) among those assigned sacubitril/valsartan versus 29.9 (SE, 0.5) mL/min/1.73 m2 among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m2. Effects were similar in all prespecified subgroups. There was also no significant difference in estimated GFR at 3, 6, 9, or 12 months and no clear difference in urinary albumin:creatinine ratio between treatment arms (study average difference, -9%; 95% CI, -18 to 1). However, compared with irbesartan, allocation to sacubitril/valsartan reduced study average systolic and diastolic blood pressure by 5.4 (95% CI, 3.4-7.4) and 2.1 (95% CI, 1.0-3.3) mm Hg and levels of troponin I and N terminal of prohormone brain natriuretic peptide (tertiary end points) by 16% (95% CI, 8-23) and 18% (95% CI, 11-25), respectively. The incidence of serious adverse events (29.5% versus 28.5%; rate ratio, 1.07; 95% CI, 0.75-1.53), nonserious adverse reactions (36.7% versus 28.0%; rate ratio, 1.35; 95% CI, 0.96-1.90), and potassium ≥5.5 mmol/L (32% versus 24%, P=0.10) was not significantly different between randomized groups. CONCLUSIONS: Over 12 months, sacubitril/valsartan has similar effects on kidney function and albuminuria to irbesartan, but it has the additional effect of lowering blood pressure and cardiac biomarkers in people with chronic kidney disease. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com . Unique identifier: ISRCTN11958993.

Declining comorbidity-adjusted mortality rates in English patients receiving maintenance renal replacement therapy.

We aimed to compare long-term mortality trends in end-stage renal disease versus general population controls after accounting for differences in age, sex and comorbidity. Cohorts of 45,000 patients starting maintenance renal replacement therapy (RRT) and 5.3 million hospital controls were identified from two large electronic hospital inpatient data sets: the Oxford Record Linkage Study (1965-1999) and all-England Hospital Episode Statistics (2000-2011). All-cause and cause-specific three-year mortality rates for both populations were calculated using Poisson regression and standardized to the age, sex, and comorbidity structure of an average 1970-2008 RRT population. The median age at initiation of RRT in 1970-1990 was 49 years, increasing to 61 years by 2006-2008. Over that period, there were increases in the prevalence of vascular disease (from 10.0 to 25.2%) and diabetes (from 6.7 to 33.9%). After accounting for age, sex and comorbidity differences, standardized three-year all-cause mortality rates in treated patients with end-stage renal disease between 1970 and 2011 fell by about one-half (relative decline 51%, 95% confidence interval 41-60%) steeper than the one-third decline (34%, 31-36%) observed in the general population. Declines in three-year mortality rates were evident among those who received a kidney transplant and those who remained on dialysis, and among those with and without diabetes. These data suggest that the full extent of mortality rate declines among RRT patients since 1970 is only apparent when changes in comorbidity over time are taken into account, and that mortality rates in RRT patients appear to have declined faster than in the general population.

Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation.

Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.

Biliary Tract and Liver Complications in Polycystic Kidney Disease.

Polycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. We tested this hypothesis using all England Hospital Episode Statistics data (1998-2012), within which we identified 23,454 people with ADPKD and 6,412,754 hospital controls. Hospitalization rates for biliary tract disease, serious liver complications, and a range of other known ADPKD manifestations were adjusted for potential confounders. Compared with non-ADPKD hospital controls, those with ADPKD had higher rates of admission for biliary tract disease (rate ratio [RR], 2.24; 95% confidence interval [95% CI], 2.16 to 2.33) and serious liver complications (RR, 4.67; 95% CI, 4.35 to 5.02). In analyses restricted to those on maintenance dialysis or with a kidney transplant, RRs attenuated substantially, but ADPKD remained associated with biliary tract disease (RR, 1.19; 95% CI, 1.08 to 1.31) and perhaps with serious liver complications (RR, 1.15; 95% CI, 0.98 to 1.33). The ADPKD versus non-ADPKD RRs for biliary tract disease were larger for men than women (heterogeneity P<0.001), but RRs for serious liver complications appeared higher in women (heterogeneity P<0.001). Absolute excess risk of biliary tract disease associated with ADPKD was larger than that for serious liver disease, cerebral aneurysms, and inguinal hernias but less than that for urinary tract infections. Overall, biliary tract disease seems to be a distinct and important extrarenal complication of ADPKD.