Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients.

INTRODUCTION: Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage coexisting comorbidities. However, some studies suggest that a large number of medications could also detrimentally affect patients' health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of types of medications and HRQoL in dialysis patients. METHODS: A multicentre cohort study was conducted among dialysis patients from Dutch dialysis centres 3 months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of types of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0-100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0-30) measured with the Dialysis Symptoms Index and self-rated health (range 0-100) measured with the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including comorbidity. Analyses for MCS and number of symptoms were performed after categorizing patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. RESULTS: A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and the mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95% confidence interval [95% CI]: -0.9 to -0.2; p = 0.002). MCS was 4.9 point lower (95% CI: -8.8 to -1.0; p = 0.01) and 1.0 point lower (95% CI: -5.1-3.1; p = 0.63) for the highest and middle tertiles of medications, respectively, than for the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms than in the lowest tertile (95% CI: 1.5-6.6; p = 0.002), but no significant difference in the number of symptoms was observed between the middle and lowest tertiles. Self-rated health was 1.5 point lower for each medication (95% CI: -2.2 to -0.7; p < 0.001). DISCUSSION/CONCLUSION: After adjustment for comorbidity and other confounders, a higher number of medications were associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms.

Long-term clinical parameters after switching to nocturnal haemodialysis: a Dutch propensity-score-matched cohort study comparing patients on nocturnal haemodialysis with patients on three-times-a-week haemodialysis/haemodiafiltration.

OBJECTIVES: Nocturnal haemodialysis (NHD), characterised by 8-hour sessions ≥3 times a week, is known to improve clinical parameters in the short term compared with conventional-schedule haemodialysis (HD), generally 3×3.5-4 hours a week. We studied long-term effects of NHD and used patients on conventional HD/haemodiafiltration (HDF) as controls. DESIGN: Four-year prospective follow-up of patients who switched to NHD; we compared patients with patients on HD/HDF using propensity score matching. SETTING: 28 Dutch dialysis centres. PARTICIPANTS: We included 159 patients starting with NHD any time since 2004, aged 56.7±12.9 years, with median dialysis vintage 2.3 (0.9-5.1) years. We propensity-score matched 100 patients on NHD to 100 on HD/HDF. PRIMARY AND SECONDARY OUTCOME MEASURES: Control of hypertension (predialysis blood pressure, number of antihypertensives), phosphate (phosphate, number of phosphate binders), nutritional status and inflammation (albumin, C reactive protein and postdialysis weight) and anaemia (erythropoiesis-stimulating agent (ESA) resistance). RESULTS: Switching to NHD was associated with a non-significant reduction of antihypertensives compared with HD/HDF (OR <2 types 2.17, 95% CI 0.86 to 5.50, P=0.11); and a prolonged lower need for phosphate binders (OR <2 types 1.83, 95% CI 1.10 to 3.03, P=0.02). NHD was not associated with significant changes in blood pressure or phosphate. NHD was associated with significantly higher albumin over time compared with HD/HDF (0.70 g/L/year, 95% CI 0.10 to 1.30, P=0.02). ESA resistance decreased significantly in NHD compared with HD/HDF, resulting in a 33% lower ESA dose in the long term. CONCLUSIONS: After switching to NHD, the lower need for antihypertensives, phosphate binders and ESA persists for at least 4 years. These sustained improvements in NHD contrast significantly with the course of these parameters during continued treatment with conventional-schedule HD and HDF. NHD provides an optimal form of dialysis, also suitable for patients expected to have a long waiting time for transplantation or those convicted to indefinite dialysis.

Investigation into cardiac sympathetic innervation during the commencement of haemodialysis in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) who undergo chronic haemodialysis (HD) show altered sympathetic tone, which is related to a higher cardiovascular mortality. The purpose of this study was to investigate the effect of transition from pre-HD to HD on cardiac sympathetic innervation. METHODS: Eighteen patients aged 58 ± 18 years (mean ± standard deviation [SD]), 13 males and five females, with stage 5 CKD and nine healthy control subjects aged 52 ± 17 (mean ± SD), three males and six females, were included in this prospective study between May 2010 and December 2013. All patients underwent 123I-labelled meta-iodobenzylguanidine (123I-MIBG) scintigraphy for cardiac sympathetic innervation and electrocardiographically gated adenosine stress and rest 99mTc-labelled tetrofosmin single-photon emission computed tomography for myocardial perfusion imaging prior to (pre-HD) and 6 months after the start of HD. Results of 123I-MIBG scans in patients were compared to controls. Impaired cardiac sympathetic innervation was defined as late heart-to-mediastinum ratio (HMR) < 2.0. RESULTS: Mean late HMR was lower in patients during HD (2.3) than in controls (2.9) (p = 0.035); however, in patients it did not differ between pre-HD and after the start of HD. During HD, two patients showed new sympathetic innervation abnormalities, and in three patients innervation abnormalities seemed to coincide with myocardial perfusion abnormalities. CONCLUSIONS: CKD patients show cardiac sympathetic innervation abnormalities, which do not seem to progress during the maintenance HD. The relationship between sympathetic innervation abnormalities and myocardial perfusion abnormalities in HD patients needs further exploration.

Screening for elevated albuminuria and subsequently hypertension identifies subjects in which treatment may be warranted to prevent renal function decline.

Background: We investigated whether initial population screening for elevated albuminuria with subsequent screening for hypertension in case albuminuria is elevated may be of help to identify subjects at risk for accelerated decline in kidney function. Methods: We included subjects who participate in the PREVEND observational, general population-based cohort study and had two or more glomerular filtration rate (eGFR) measurements available during follow-up. Elevated albuminuria was defined as an albumin concentration ≥20 mg/L in a first morning urine sample confirmed by an albumin excretion ≥30 mg/day in two 24-h urines. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or use of blood pressure-lowering drugs. eGFR was estimated with the CKD-EPI creatinine-cystatin C equation. Results: Overall, 6471 subjects were included with a median of 4 [95% confidence interval (CI) 2-5] eGFR measurements during a follow-up of 11.3 (95% CI 4.0-13.7) years. Decline in eGFR was greater in the subgroups with elevated albuminuria. This held true, not only in subjects with known hypertension (-1.84 ± 2.27 versus -1.16 ± 1.45 mL/min/1.73 m 2 per year, P < 0.05), but also in subjects with newly diagnosed hypertension (-1.59 ± 1.55 versus -1.14 ± 1.38 mL/min/1.73 m 2 per year, P < 0.05) and in subjects with normal blood pressure (-1.18 ± 1.85 versus -0.81 ± 1.02 mL/min/1.73 m 2 per year in subjects, P < 0.05). This effect was most pronounced in the population ≥55 years of age and male subjects. In addition, subjects with elevated albuminuria had higher blood pressure than subjects with normoalbuminuria, and in subjects with elevated albuminuria as yet undiagnosed hypertension was twice as prevalent as diagnosed hypertension. Conclusions: Initial screening for elevated albuminuria followed by screening for hypertension may help to detect subjects with increased risk for a steeper decline in kidney function.

Impact of the Introduction of Calcimimetics on Timing of Parathyroidectomy in Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: Hyperparathyroidism (HPT), both secondary and tertiary, is common in patients with end-stage renal disease, and is associated with severe bone disorders, cardiovascular complications, and increased mortality. Since the introduction of calcimimetics in 2004, treatment of HPT has shifted from surgery to predominantly medical therapy. OBJECTIVE: The aim of this study was to evaluate the impact of this change of management on the HPT patient population before undergoing (sub-)total parathyroidectomy (PTx). METHODS: Overall, 119 patients with secondary or tertiary HPT undergoing PTx were included in a retrospective, single-center cohort. Group A, who underwent PTx before January 2005, was compared with group B, who underwent PTx after January 2005. Patient characteristics, time interval between HPT diagnosis and PTx, and postoperative complications were compared. RESULTS: Group A comprised 70 (58.8 %) patients and group B comprised 49 (41.2 %) patients. The median interval between HPT diagnosis and PTx was 27 (interquartile range [IQR] 12.5-48.0) and 49 (IQR 21.0-75.0) months for group A and B, respectively (p = 0.007). Baseline characteristics were similar among both groups. The median preoperative serum parathyroid hormone (PTH) level was 936 pg/mL (IQR 600-1273) for group A versus 1091 pg/mL (IQR 482-1373) for group B (p = 0.38). PTx resulted in a dramatic PTH reduction (less than twofold the upper limit: A, 80.0 %; B, 85.4 %), and postoperative complication rates were low in both groups (A: 7.8 %; B: 10.2 %) [p = 0.66]. CONCLUSIONS: The introduction of calcimimetics in 2004 is associated with a significant 2-year delay of surgery with continuously elevated preoperative PTH levels, while parathyroid surgery, even in a fragile population, is considered a safe and effective procedure.

Screening for albuminuria with subsequent screening for hypertension and hypercholesterolaemia identifies subjects in whom treatment is warranted to prevent cardiovascular events.

BACKGROUND: In the general population, many subjects have yet unrecognized hypertension and hypercholesterolaemia, and are thus not treated. We investigated whether population screening for elevated albuminuria can identify subjects with previously unrecognized hypertension and/or hypercholesterolaemia at high risk for cardiovascular (CV) disease. METHODS: Included were 8143 subjects (28-75 years) that participate in the PREVEND study, a general population-based, observational cohort study. Elevated albuminuria was defined as an albumin concentration ≥ 20 mg/L in a first morning urine sample confirmed by an albumin excretion ≥ 30 mg/day in two 24-h urine samples. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg, and hypercholesterolaemia as serum total cholesterol ≥ 6.2 mmol/L, or as HDL cholesterol < 0.9 mmol/L and a total/HDL cholesterol ratio of ≥ 6. Combined CV morbidity and mortality during follow-up was adopted as outcome. RESULTS: In the group with, as well as in the group without elevated albuminuria, the number of subjects with yet unrecognized hypertension and hypercholesterolaemia was at least 2-fold higher than the number of subjects known with these CV risk factors. Mean follow-up was 7.1 ± 1.5 years, during which 445 CV events occurred. The hazard ratio for CV events was significantly elevated in the subjects with, compared with those without elevated albuminuria, independent of whether they had no CV risk factor present, a CV risk factor known or a CV risk factor newly discovered. The CV event rate in those with an elevated albuminuria crossed the recommended threshold to start antihypertensive or anticholesterolaemic treatment, not only when the CV risk factor was known, but also in the subgroup with newly diagnosed CV risk factor. In subjects with a newly discovered CV risk factor without albuminuria, absolute CV risk was significantly lower. CONCLUSIONS: Screening for elevated albuminuria and subsequent screening for CV risk factors identify subjects with yet unknown CV risk factors at high risk for CV disease that are likely to benefit from early preventive treatment.

Screening for chronic kidney disease can be of help to prevent atherosclerotic end-organ damage.

Atherosclerotic damage to the kidney is one of the most prevalent causes of chronic kidney disease and ultimately kidney failure. It frequently coincides with atherosclerotic damage to the heart, the brain and the lower extremities. In fact, the severity of the damage in the various end organs runs in parallel. As damage to the kidney is easy to measure by monitoring albuminuria and eGFR, and as the early phases of kidney damage frequently precede the alarming symptomatology in the heart, brain and peripheral vasculature, we argue that the nephrologist should consider taking the lead in better organizing early detection and management of CKD. The nephrologist can guide the general practitioner and general health care workers to offer better preventive care to the subjects at risk of progressive atherosclerotic end-organ damage.

Selection on albuminuria enhances the efficacy of screening for cardiovascular risk factors.

BACKGROUND: As many subjects with a cardiovascular (CV) risk factor are undiagnosed, guidelines to prevent cardiovascular disease argue for case finding on those risk factors. Such an approach is, however, labour and cost intensive. An elevated urinary albumin loss is an early marker of vascular damage and is associated with an increased CV risk. As albuminuria is easy to measure, we tested whether a screening approach in which detailed risk factor measurement is done only after selection of subjects with an elevated albuminuria results in a higher yield of subjects at risk. METHODS: A random sample of the general population as investigated in the Prevention of Renal and Vascular End-Stage Disease study was used. Plasma glucose, blood pressure, serum cholesterol and renal function were measured in an overall random sample of the population, in subgroups according to their urinary albumin concentration (UAC) of one first morning urine void and in subgroups in whom the elevated albuminuria level was confirmed with two 24 h urine collections for measurement of urinary albumin excretion (UAE). RESULTS: In the overall population, the number of subjects with any newly found CV risk factor was higher than the number of subjects already known with any CV risk factor (n = 1331 versus 370; 39.2 versus 10.9%). The prevalence of subjects with any newly diagnosed CV risk factor was higher in the group of 267 subjects with a first morning UAC of ≥ 20 mg/L (61.0%; P < 0.05) compared to the overall population (39.2%). Although the sensitivity of a UAC ≥ 20 mg/L to detect a subject with at least one CV risk factor was relatively low (12%), the specificity was very high (96%). The positive predictive value was 70%. When the elevated UAC could be confirmed in two subsequent 24-h urine collections, the diagnostic yield still further improved. CONCLUSION: The prevalence of undiagnosed CV risk factors in the general population is much higher than the prevalence of known risk factors. After a selection of subjects with an elevated albuminuria, the relative prevalence of subjects with newly diagnosed CV risk factors increases while the number of subjects to test for presence of CV risk factors is smaller. Such an approach facilitates a more effective and simple strategy for risk factor screening.