Patterns and characteristics of cognitive functioning in older patients approaching end stage kidney disease, the COPE-study.

BACKGROUND: The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT). METHODS: The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed. RESULTS: The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values < 0.003). A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed. CONCLUSION: Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.

Tenosynovitis caused by Mycobacterium malmoense in two kidney transplant recipients and review of the literature.

We report two unrelated cases of tenosynovitis caused by Mycobacterium malmoense in kidney transplant recipients. Both patients received immunosuppression and were referred to our tertiary hospital because of persisting complaints lasting >6 months not responding to corticosteroids or surgery. The mycobacterial cultures were positive for the slow-growing M. malmoense after several weeks of incubation. The patient in Case 1 was treated with a combination of surgical debridement and antibiotics, whereas the patient in Case 2 was only treated surgically. Both cases illustrate the doctor's delay in diagnosing mycobacterial infections, and remind us that nontuberculous mycobacterial infections should be part of the differential diagnosis of tenosynovitis, especially in immunocompromised patients.

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

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).

Echocardiographical determinants of an abnormal spatial QRS-T angle in chronic dialysis patients.

BACKGROUND: The spatial QRS-T angle describes the relation between ventricular depolarization and repolarization. Having a wide (abnormal) angle is considered an important predictor of arrhythmic events. Given the high incidence of sudden cardiac death in dialysis patients, this parameter is of particular interest in this patient group. The objective of this study was to assess the association of (modifiable) echocardiographic parameters and an abnormal spatial QRS-T angle in dialysis patients. METHODS: A total of 94 consecutive dialysis patients were included. In all patients a 12-lead electrocardiogram (ECG), a two-dimensional echocardiogram and routine blood samples were obtained. The spatial QRS-T angle was then calculated from the 12-lead ECG. An abnormal spatial QRS-T angle was defined as ≥130° in males and ≥116° in females. RESULTS: An abnormal spatial QRS-T angle was present in 27 (29%) patients. Patients with an abnormal spatial angle had a lower left ventricular ejection fraction (LVEF) of 47 ± 7 versus 55 ± 6% (P < 0.001) and had a higher left ventricular (LV) dyssynchrony, with a septal to lateral (S-L) delay of peak systolic velocity of 70 inter quartile range (iIQR) (40, 100) ms versus 30 IQR (10, 70) ms (P = 0.001), respectively. Multivariate logistic regression analysis controlling for possible confounders demonstrated that LVEF [odds ratio (OR) 0.82; 95% confidence interval (CI) 0.72-0.93, P = 0.001] and LV dyssynchrony (OR 1.19 per 10 ms; 95% CI 1.03-1.38, P = 0.02) were independent determinants of an abnormal spatial QRS-T angle in this patient group. CONCLUSIONS: LVEF and dyssynchrony are echocardiographic determinants of an abnormal spatial QRS-T angle in dialysis patients and might therefore represent a potential target for the prevention of sudden cardiac death in these patients.

CT coronary angiography is feasible for the assessment of coronary artery disease in chronic dialysis patients, despite high average calcium scores.

PURPOSE: Significant obstructive coronary artery disease (CAD) is common in asymptomatic dialysis patients. Identifying these high risk patients is warranted and may improve the prognosis of this vulnerable patient group. Routine catheterization of incident dialysis patients has been proposed, but is considered too invasive. CT-angiography may therefore be more appropriate. However, extensive coronary calcification, often present in this patient group, might hamper adequate lumen evaluation. The objective of this study was to assess the feasibility of CT-angiography in this patient group. METHODS: For this analysis all patients currently participating in the ICD2 trial (ISRCTN20479861), with no history of PCI or CABG were included. The major epicardial vessels were evaluated on a segment basis (segment 1-3, 5-8, 11 and 13) by a team consisting of an interventional and an imaging specialist. Segments were scored as not significant, significant and not interpretable. RESULTS: A total of 70 dialysis patients, with a mean age of 66±8 yrs and predominantly male (70%) were included. The median calcium score was 623 [79, 1619]. Over 90% of the analyzed segments were considered interpretable. The incidence of significant CAD on CT was 43% and was associated with cardiovascular events during follow-up. The incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in patients with no significant CAD (p<0.01). CONCLUSION: Despite the high calcium scores CT-angiography is feasible for the evaluation of the extent of CAD in dialysis patients. Moreover the presence of significant CAD on CT was associated with events during follow-up.

Incremental prognostic value of an abnormal baseline spatial QRS-T angle in chronic dialysis patients.

AIMS: In order to improve the abysmal outcome of dialysis patients, it is critical to identify patients with a high mortality risk. The spatial QRS-T angle, which can be easily calculated from the 12 lead electrocardiogram (ECG), might be useful in the prognostication in dialysis patients. The objective of this study was to establish the prognostic value of the spatial QRS-T angle. METHODS AND RESULTS: All patients who initiated dialysis therapy between 2002 and 2009 in the hospitals of Leiden (LUMC) and Amsterdam (AMC) at least 3 months on dialysis were included. The spatial QRS-T angle was calculated, from a routinely acquired ECG, and its relationship with mortality was assessed. An abnormal spatial QRS-T angle was defined as ≥ 130° in men and ≥ 116° in women. In total, 277 consecutive patients (172 male, mean age 56.3 ± 17.0) were included. An abnormal spatial QRS-T angle was associated with a higher risk of death from all causes [hazard ratio (HR) 2.33; 95% confidence interval (CI) 1.46-3.70] and especially a higher risk of sudden cardiac death (HR 2.99; 95% CI 1.04-8.60). Furthermore, an abnormal spatial QRS-T angle was of incremental prognostic value, when added to a risk model consisting of known risk factors. CONCLUSION: In chronic dialysis patients the spatial QRS-T angle is a significant and independent predictor of all-cause and especially sudden cardiac death. It implies that this parameter can be used to identify high risk patients.

Left ventricular diastolic dysfunction in dialysis patients assessed by novel speckle tracking strain rate analysis: prevalence and determinants.

Background. Diastolic dysfunction is common among dialysis patients and is associated with increased morbidity and mortality. Novel echocardiographic speckle tracking strain analysis permits accurate assessment of left ventricular diastolic function, independent of loading conditions and taking all myocardial segments into account. The aim of the study was to evaluate the prevalence of diastolic dysfunction in chronic dialysis patients using this novel technique, and to identify its determinants among clinical and echocardiographic variables. Methods. Patients currently enrolled in the ICD2 study protocol were included for this analysis. Next to conventional echo measurements diastolic function was also assessed by global diastolic strain rate during isovolumic relaxation (SRIVR). Results. A total of 77 patients were included (age 67 ± 8 years, 74% male). When defined as E/SRIVR ≥236, the prevalence of diastolic dysfunction was higher compared to more conventional measurements (48% versus 39%). Left ventricular mass (OR 1.02, 95% CI 1.00-1.04, P = 0.014) and pulse wave velocity (OR 1.34, 95% CI 1.07-1.68, P = 0.01) were independent determinants of diastolic dysfunction. Conclusion. Diastolic dysfunction is highly prevalent among dialysis patients and might be underestimated using conventional measurements. Left ventricular mass and pulse wave velocity were the only determinants of diastolic dysfunction in these patients.

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.

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

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.

An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype among renal transplant recipients: interhuman transmission or a common environmental source?

BACKGROUND: An outbreak of Pneumocystis jiroveci pneumonia (PCP) occurred among renal transplant recipients attending the outpatient department at the Leiden University Medical Centre (Leiden, The Netherlands) from 1 March 2005 through 1 February 2006. Clinical, epidemiological, and molecular data were analyzed to trace the outbreak's origin. METHODS: Renal transplant recipients with a clinical suspected diagnosis of PCP were included in the study. The diagnosis had to be confirmed by direct microscopy or real-time polymerase chain reaction of the dihydropteroate synthase gene in a bronchoalveolar fluid specimen. To detect contacts between patients, a transmission map was constructed. A case-control analysis was performed to asses whether infection was associated with certain wardrooms. Genotyping of Pneumocystis isolates was performed by sequence analysis of the internal transcribed spacer (ITS) number 1 and 2 gene regions. RESULTS: Twenty-two confirmed PCP cases were identified; approximately 0-1 would have been expected over the same time period. No risk factor was predominantly present, and standard immunosuppressive regimens had not changed. Liver transplant recipients who used the same outpatient facilities had not acquired PCP. The transmission map findings were compatible with interhuman transmission on multiple occasions. The case-control study did not point to wardrooms as a common source. Genotyping by sequencing of the ITS1 and ITS2 gene regions revealed type Ne in 12 of 16 successfully typed samples. Genotype Ne was found in only 2 of 12 reference samples. CONCLUSIONS: The clinical data and genotyping results are compatible with either interhuman transmission or an environmental source of infection. More complex models may account for PCP clusters.

Hypophosphatemia: an update on its etiology and treatment.

Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.