Marjolijn van Buren

Multifactorial intervention with nurse practitioners does not change cardiovascular outcomes in patients with chronic kidney disease

Strict implementation of guidelines directed at multiple targets reduces vascular risk in diabetic patients. Whether this also applies to patients with chronic kidney disease (CKD) is uncertain. To evaluate this, the MASTERPLAN Study randomized 788 patients with CKD (estimated GFR 20-70 ml/min) to receive additional intensive nurse practitioner support (the intervention group) or nephrologist care (the control group). The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death. During a mean follow-up of 4.62 years, modest but significant decreases were found for blood pressure, LDL cholesterol, anemia, proteinuria along with the increased use of active vitamin D or analogs, aspirin and statins in the intervention group compared to the controls. No differences were found in the rate of smoking cessation, weight reduction, sodium excretion, physical activity, or glycemic control. Intensive control did not reduce the rate of the composite end point (21.3/1000 person-years in the intervention group compared to 23.8/1000 person-years in the controls (hazard ratio 0.90)). No differences were found in the secondary outcomes of vascular interventions, all-cause mortality or end-stage renal disease. Thus, the addition of intensive support by nurse practitioner care in patients with CKD improved some risk factor levels, but did not significantly reduce the rate of the primary or secondary end points.

Prevention of sudden cardiac death: rationale and design of the Implantable Cardioverter Defibrillators in Dialysis patients (ICD2) Trial – a prospective pilot study

ABSTRACT Objective: Sudden cardiac (arrhythmic) death (SCD) is the single largest cause of death in dialysis patients. Prophylactic Implantable Cardioverter Defibrillator (ICD) therapy reduces SCD and reduces all-cause mortality in several groups of patients at high risk for arrhythmic death. Whether this also applies to dialysis patients is unknown. Research design and methods: The Implantable Cardioverter Defibrillator in Dialysis patients (ICD2) trial is a prospective randomised controlled study. It has been designed to evaluate the efficacy and safety of prophylactic ICD therapy in reducing sudden cardiac death rates in dialysis patients aged 55–80 years. A total of 200 patients will be included. The primary endpoint of the study is sudden cardiac (arrhythmic) death. The mean follow-up time will be 4 years. Trial registration: ‘The Netherlands Trial Register’ – ISRCTN20479861 Conclusion: The ICD2 trial – a pilot study – will be the first study to evaluate the possible benefit of ICD therapy for the primary prevention of sudden cardiac death in dialysis patients.

Nurse Practitioner Care Improves Renal Outcome in Patients with CKD

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m(2) per year less than in the control group (P=0.01). In conclusion, additional support by nurse practitioners attenuated the decline of kidney function and improved renal outcome in patients with CKD.

The current status of interventions aiming at reducing sudden cardiac death in dialysis patients.

Mortality in dialysis patients is extremely high, with an annual death rate of approximately 23%. Sudden cardiac death (SCD) is the single largest cause of death in dialysis patients accounting for approximately 60% of all cardiac deaths and 25% of all-cause mortality. Interventions aiming at reducing cardiovascular mortality, especially SCD, in dialysis patients are therefore extremely important and clinically highly relevant. The purpose of this review is to give an outline of the epidemiology of SCD in dialysis patients and to provide a comprehensive overview of several interventional strategies (medical therapies, changing dialysis modality, and revascularization). Furthermore, it will discuss the current knowledge regarding the value of preventive implantable cardioverter defibrillator implantation and address future implications of the interventional strategies mentioned.

Functional and Cognitive Impairment, Frailty, and Adverse Health Outcomes in Older Patients Reaching ESRD-A Systematic Review

BACKGROUND AND OBJECTIVES Older patients reaching ESRD have a higher risk of adverse health outcomes. We aimed to determine the association of functional and cognitive impairment and frailty with adverse health outcomes in patients reaching ESRD. Understanding these associations could ultimately lead to prediction models to guide tailored treatment decisions or preventive interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched MEDLINE, Embase, Web of Science, CENTRAL, CINAHL, PsycINFO, and COCHRANE for original studies published until February 8, 2016 reporting on the association of functional or cognitive impairment or frailty with adverse health outcome after follow-up in patients reaching ESRD either with or without RRT. RESULTS Of 7451 identified citations, we included 30 articles that reported on 35 associations. Mean age was >60 years old in 73% of the studies, and geriatric conditions were highly prevalent. Twenty-four studies (80%) reported on functional impairment, seven (23%) reported on cognitive impairment, and four (13%) reported on frailty. Mortality was the main outcome measure in 29 studies (97%), and one study assessed functional status trajectory. In 34 of 35 (97%) associations reported, functional or cognitive impairment or frailty was significantly and independently associated with adverse health outcomes. The majority of studies (83%) were conducted in selected patient populations, mainly patients on incident dialysis. CONCLUSIONS Functional and cognitive impairment and frailty in patients reaching ESRD are highly prevalent and strongly and independently associated with adverse health outcomes, and they may, therefore, be useful for risk stratification. More research into their prognostic value is needed.

Quality of care in patients with chronic kidney disease is determined by hospital specific factors

BACKGROUND Guidelines have set goals for risk factor management in chronic kidney disease (CKD) patients. These goals are often not met. In this analysis, we set out to assess the quality of risk factor management in CKD and to identify factors that determine the quality of care (QoC). For that purpose, baseline data of the MASTERPLAN (Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse practitioners) study have been used. MASTERPLAN is a multicentre study which evaluates the effect of a multifactorial intervention in prevalent CKD patients on cardiovascular (CV) events and progression of kidney failure. METHODS QoC was quantified using a score based on the number of 11 defined treatment goals on target. The maximum score per patient was 11. RESULTS The average (±SD) QoC score was 6.7 (±1.5). The average score per centre ranged from 5.9 to 6.9. In a multivariable analysis, centre proved to be a significant, independent determinant of QoC with a difference up to 0.7 between centres. This difference remained when adjustments were made for those risk factors primarily treated by pharmacotherapy. Other factors that were significantly related to the QoC were estimated glomerular filtration rate, Caucasian race, diabetes mellitus, diabetic nephropathy as cause of kidney disease and previous kidney transplantation. CONCLUSIONS In CKD patients, risk factors for progression of kidney failure and CV events were inadequately controlled. Treatment centre proved to be an important determinant of QoC. This data may point towards the physicians interest and preference as important determinants of QoC. This is a potentially modifiable determinant of the quality of patient care [Trial registration ISRCTN registry: 73187232 (http://isrctn.org)].

Serum Cardiac Troponin-I is Superior to Troponin-T as a Marker for Left Ventricular Dysfunction in Clinically Stable Patients with End-Stage Renal Disease

Background Serum troponin assays, widely used to detect acute cardiac ischemia, might be useful biomarkers to detect chronic cardiovascular disease (CVD). Cardiac-specific troponin-I (cTnI) and troponin-T (cTnT) generally detect myocardial necrosis equally well. In dialysis patients however, serum cTnT levels are often elevated, unlike cTnI levels. The present study aims to elucidate the associations of cTnI and cTnT with CVD in clinically stable dialysis patients. Methods Troponin levels were measured using 5th generation hs-cTnT assays (Roche) and STAT hs-cTnI assays (Abbott) in a cohort of dialysis patients. Serum troponin levels were divided into tertiles with the lowest tertile as a reference value. Serum troponins were associated with indicators of CVD such as left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and the presence of coronary artery disease (CAD). Associations were explored using regression analysis. Results We included 154 consecutive patients, 68±7 years old, 77% male, 70% hemodialysis. Median serum cTnT was 51ng/L (exceeding the 99th percentile of the healthy population in 98%) and median serum cTnI was 13ng/L (elevated in 20%). A high cTnI (T3) was significantly associated with a higher LVMI (Beta 31.60; p=0.001) and LVEF (Beta -4.78; p=0.005) after adjusting for confounders whereas a high serum cTnT was not. CAD was significantly associated with a high cTnT (OR 4.70 p=0.02) but not with a high cTnI. Unlike cTnI, cTnT was associated with residual renal function (Beta:-0.09; p=0.006). Conclusion In the present cohort, serum cTnI levels showed a stronger association with LVMI and LVEF than cTnT. However, cTnT was significantly associated with CAD and residual renal function, unlike cTnI. Therefore, cTnI seems to be superior to cTnT as a marker of left ventricular dysfunction in asymptomatic dialysis patients, while cTnT might be better suited to detect CAD in these patients.

Pre-dialysis decline of measured glomerular filtration rate but not serum creatinine-based estimated glomerular filtration rate is a risk factor for mortality on dialysis

Background. Monitoring of renal function is important in patients with chronic kidney disease progressing towards end-stage renal failure, both for timing the start of renal replacement therapy and for determining the prognosis on dialysis. Thus far, studies on associations between estimated glomerular filtration rate (eGFR) measurements in the pre-dialysis stage and mortality on dialysis have shown no or even inverse relations, which may result from the poor validity of serum creatinine-based estimation equations for renal function in pre-dialysis patients. As decline in renal function may be better reflected by the mean of the measured creatinine and urea clearance based on 24-h urine collections (mGFR by CCr-U), we hypothesize that in patients with low kidney function, a fast mGFR decline is a risk factor for mortality on dialysis, in contrast to a fast eGFR decline. Methods. For 197 individuals, included from the multicentre NECOSAD cohort, pre-dialysis annual decline of mGFR and eGFR was estimated with linear regression, and classified according to KDOQI as fast (>4 mL/min/1.73 m2/year) or slow (⩽4 mL/min/1.73 m2/year). Cox regression was used to adjust for potential confounders. Results. Patients with a fast mGFR decline had an increased risk of mortality on dialysis: crude hazard ratio (HR) 1.84 (95% confidence interval: 1.13–2.98), adjusted HR 1.94 (1.11–3.36). In contrast, no association was found between a fast eGFR decline in the pre-dialysis phase and mortality on dialysis: crude HR 1.20 (0.75–1.89), adjusted HR 1.14 (0.67–1.94). Conclusions. This study demonstrates the importance of mGFR decline (by CCr-U) as opposed to eGFR decline in patients with low kidney function, and gives incentive for repeated mGFR measurements in patients on pre-dialysis care.

The Cognitive decline in Older Patients with End stage renal disease (COPE) study – rationale and design

Abstract Background: Older patients with end stage renal disease (ESRD) are at increased risk for cognitive decline, but detailed studies of the magnitude of cognitive decline on dialysis or comprehensive conservative management (CCM) are lacking and the underlying pathophysiological mechanisms have poorly been studied. Objectives: To describe the rationale and design of the COPE study. Study objectives are as follows. Firstly, to examine the severity of cognitive impairment in older patients reaching ESRD before dialysis and the rate of decline after dialysis or CCM initiation. Secondly, to study the association of blood biomarkers for microvascular damage and MRI derived measurements of small vessel disease with the rate of cognitive decline. Thirdly, to examine to what extent cardiac function is related to brain structure and perfusion in patients reaching ESRD. Finally, to study the association of cognitive and functional capacity with quality of life in pre-dialysis patients, as well as after dialysis or CCM initiation. Study design and methods: The COPE study is a prospective, multicenter cohort study in the Netherlands, including prevalent and incident pre-dialysis patients ≥65 years old with eGFR ≤20 ml/min/1.73 m2, awaiting either dialysis or CCM initiation. At baseline extensive data is collected including a comprehensive geriatric assessment and laboratory tests. Brain and cardiac MRI for analysis of structural and functional abnormalities are performed at baseline and repeated following therapy change. All other measurements are repeated annually during four years of follow up, including an extra evaluation six months after initiation of dialysis. Conclusions: Knowledge of the magnitude of cognitive decline and its underlying pathophysiological mechanism, as well as its impact on functionality and quality of life can eventually help to postulate an algorithm for well balanced decision making in treatment strategies in older patients reaching ESRD. Clinical trial registration: The COPE study is registered on www.ccmo.nl (number: NL46389.058.13).