The impact of symptoms on health-related quality of life in elderly pre-dialysis patients: effect and importance in the EQUAL study.

BACKGROUND: Quality of life (QoL) is an important outcome in chronic kidney disease (CKD). Patients feel that symptoms are an important determinant of QoL. However, this relation is unknown. The aims of this study were to investigate the impact of the number and severity of symptoms on QoL in elderly pre-dialysis patients, assessed by both the effect of symptoms and their importance relative to kidney function, and other clinical variables on QoL. METHODS: The European Quality study (EQUAL study) is an ongoing European prospective follow-up study in late Stage 4/5 CKD patients aged ≥65 years. We used patients included between March 2012 and December 2015. Patients scored their symptoms with the Dialysis Symptom Index, and QoL with the research and development-36 (RAND-36) item Health Survey (RAND-36). The RAND-36 results in a physical component summary (PCS) and a mental component summary (MCS). We used linear regression to estimate the relation between symptoms and QoL at baseline and after 6 months, and to calculate the variance in QoL explained by symptoms. RESULTS: The baseline questionnaire was filled in by 1079 (73%) patients (median age 75 years, 66% male, 98% Caucasian), and the follow up questionnaire by 627 (42%) patients. At baseline, every additional symptom changed MCS with -0.81 [95% confidence interval (CI): -0.91 to -0.71] and PCS with -0.50 (95% CI: -0.62 to -0.39). In univariable analyses, number of symptoms explained 22% of MCS variance and 11% of PCS variance, whereas estimated glomerular filtration rate only explained 1%. CONCLUSIONS: In elderly CKD Stage 4/5 patients, symptoms have a substantial impact on QoL. This indicates symptoms should have a more prominent role in clinical decision-making.

Vitamin K antagonist use and mortality in dialysis patients.

Background: The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment. Methods: We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use. Results: Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increased mortality risk after adjustment. Conclusion: Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication.

Dyslipidemia and risk of renal replacement therapy or death in incident pre-dialysis patients.

Globally the number of patients on renal replacement therapy (RRT) is rising. Dyslipidemia is a potential modifiable cardiovascular risk factor, but its effect on risk of RRT or death in pre-dialysis patients is unclear. The aim of this study was to assess the association between dyslipidemia and risk of RRT or death among patients with CKD stage 4-5 receiving specialized pre-dialysis care, an often under represented group in clinical trials. Of the 502 incident pre-dialysis patients (>18 y) in the Dutch PREPARE-2 study, lipid levels were available in 284 patients and imputed for the other patients. During follow up 376 (75%) patients started RRT and 47 (9%) patients died. Dyslipidemia was defined as total cholesterol ≥5.00 mmol/L, LDL cholesterol ≥2.50 mmol/L, HDL cholesterol <1.00 mmol/L, HDL/LDL ratio <0.4, or triglycerides (TG) ≥2.25 mmol/L, and was present in 181 patients and absent in 93 patients. After multivariable adjustment Cox regression analyses showed a HR (95% CI) for the combined endpoint for dyslipidemia of 1.12 (0.85-1.47), and for high LDL of 1.20 (0.89-1.61). All other HRs were smaller. In conclusion, we did not find an association between dyslipidemia or the separate lipid levels and RRT or death in CKD patients on specialized pre-dialysis care.

Effect of dual compared to no or single renin-angiotensin system blockade on risk of renal replacement therapy or death in predialysis patients: PREPARE-2 study.

Current guidelines on hypertension treatment in chronic kidney disease (CKD) patients discourage combined angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II receptor blocker (ARB) use due to the risk of an increased kidney function decline. However, dual compared to single renin-angiotensin system (RAS) blockade may have more efficacy with regard to hypertension and proteinuria. Among incident predialysis patients (CKD 4-5), we compared dual with no or single RAS blockade regarding kidney function decline and risk of renal replacement therapy (RRT) or death. In a multicenter cohort study, 495 incident predialysis patients (>18 years) were included between 2004 and 2011 and followed until RRT, death, or October 2016. At baseline, patients were divided into four categories: nonuser, single or dual user of ACEi and/or ARB. Cox models were used to estimate the hazard ratio for the combined end point RRT or death. Differences in decline of kidney function among the four drug groups were compared with a linear mixed model. A total of 119 patients were nonusers, 164 ACEi users, 133 ARB users, and 79 dual RAS users. Compared to nonusers, the multivariable adjusted hazard ratio (95% confidence interval) for the combined end point was 0.75 (0.65 to 0.86) for ACEi users, 0.87 (0.76 to 1.00) for ARB users, and 0.79 (0.67 to 0.94) for dual RAS users. The average annual decline in kidney function did not differ among the four groups. We observed in predialysis patients that compared to no RAS blockade, both dual RAS blockade and single ACEi use were associated with about 20%-25% lower risk of RRT or death, without difference in kidney function decline.

Obesity and risk of death or dialysis in younger and older patients on specialized pre-dialysis care.

BACKGROUND: Obesity is associated with increased mortality and accelerated decline in kidney function in the general population. Little is known about the effect of obesity in younger and older pre-dialysis patients. The aim of this study was to assess the extent to which obesity is a risk factor for death or progression to dialysis in younger and older patients on specialized pre-dialysis care. METHOD: In a multicenter Dutch cohort study, 492 incident pre-dialysis patients (>18y) were included between 2004-2011 and followed until start of dialysis, death or October 2016. We grouped patients into four categories of baseline body mass index (BMI): <20, 20-24 (reference), 25-29, and ≥30 (obesity) kg/m2 and stratified patients into two age categories (<65y or ≥65y). RESULTS: The study population comprised 212 patients younger than 65 years and 280 patients 65 years and older; crude cumulative risk of dialysis and mortality at the end of follow-up were 66% and 4% for patients <65y and 64% and 14%, respectively, for patients ≥65y. Among the <65y patients, the age-sex standardized combined outcome rate was 2.3 times higher in obese than those with normal BMI, corresponding to an excess rate of 35 events/100 patient-years. After multivariable adjustment the hazard ratios (HR) (95% CI) for the combined endpoint by category of increasing BMI were, for patients <65y, 0.92 (0.41-2.09), 1 (reference), 1.76 (1.16-2.68), and 1.81 (1.17-2.81). For patients ≥65y the BMI-specific HRs were 1.73 (0.97-3.08), 1 (reference), 1.25 (0.91-1.71) and 1.30 (0.79-1.90). In the competing risk analysis, taking dialysis as the event of interest and death as a competing event, the BMI-specific multivariable adjusted subdistribution HRs (95% CI) were, for patients <65y, 0.90 (0.38-2.12), 1 (reference), 1.47 (0.96-2.24) and 1.72 (1.15-2.59). For patients ≥65y the BMI-specific SHRs (95% CI) were 1.68 (0.93-3.02), 1 (reference), 1.50 (1.05-2.14) and 1.80 (1.23-2.65). CONCLUSION: We found that obesity in younger pre-dialysis patients and being underweight in older pre-dialysis patients are risk factors for starting dialysis and for death, compared with those with a normal BMI.