Albuminuria is associated with a higher prevalence of depression in a population-based cohort study: the Maastricht Study.

Background: Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears. Methods: We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2010 and September 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview. Results: In total, 5.4% had a minor or major depressive episode. UAE was <15 mg/24 h in 81.2%, 15-<30 mg/24 h in 10.3% and ≥30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE <15 mg/24 h as reference category, the odds ratio for a minor or major depressive episode was 2.13 [95% confidence interval (CI) 1.36-3.36] for UAE 15-<30 mg/24 h and 1.81 (95% CI 1.10-2.98) for UAE ≥30 mg/24 h. The average eGFR was 88.2 ± 14.7 mL/min/1.73 m2. eGFR was not associated with the presence of a minor or major depressive episode. Results were similar when we assessed associations with depressive symptoms or clinically relevant depressive symptoms (PHQ-9 score ≥10). Conclusions: Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression.

Hemodialysis: A model for extreme physiology in a vulnerable patient population.

Hemodialysis (HD) is a lifesaving treatment for patients with end-stage renal disease, which is very efficient in the correction of abnormalities of the internal environment. However, this efficiency also induces significant hemodynamic, thermal, and respiratory stressors. These have parallels with the extreme physiologic demands which are normally mainly experienced by healthy subjects under adverse environmental conditions, with the difference that they must be endured by a vulnerable patient population. Hemodynamic stress induced by ultrafiltration leads to a decline in circulating blood volume, which may result in intradialytic hypotension (IDH) and changes in tissue perfusion, which may have long-term consequences for the function of vital organs such as the brain and the heart. Pronounced declines in central venous oxygen saturation have been observed during routine HD, which are related to the circulatory stress imposed upon the patient. Apart from patient-related factors, thermal stress induced by HD may lead to skin vasodilation, counteracting the normal hemodynamic response to hypovolemia, which has important pathophysiologic correlates in heat syncope. Lastly, respiratory stress is reflected by prolonged arterial hypoxemia during HD, which is both related to patient-related factors, but may also be partly because of the treatment itself, especially during the first 30-60 minutes. Whereas hypoxemia during HD is related to increased mortality, its role in the reduced tissue oxygen delivery during HD should be further defined. Treatment modifications, such as cool or temperature-controlled HD, may reduce circulatory and thermal stress, which also may translate into a reduced risk of long-term cardiac or cerebral damage. However, as circulatory stress is mainly time-dependent, prolonged, or more dialysis treatment may reduce the homeostatic burden on the patient.

Fluid Overload and Inflammation Axis.

Extracellular fluid overload (FO), which is assessed using bioimpedance technologies, is an important predictor of outcome in dialysis patients and in patients with early stages of chronic kidney disease. While traditional cardiovascular abnormalities are assumed to mediate this risk, recently also, the importance of noncardiovascular factors, such as systemic inflammation and malnutrition has been shown. While both FO and inflammation are independent risk factors for mortality, recent studies have shown that their combined presence can lead to a cumulative risk profile. From a pathophysiologic viewpoint, FO and inflammation can also be mutually reinforcing. Inflammation could contribute to FO by hypoalbuminemia, capillary leakage, and a (unnoticed) decline in lean and/or fat tissue mass resulting in incorrect estimation of dry weight. Reciprocally, FO could lead to inflammation by the translocation of endotoxins through a congested bowel wall or by a proinflammatory effect of tissue sodium. The relative importance of these putative factors is, however, not clear yet and epidemiological studies have shown no clear temporal direction regarding the relationship between FO and inflammation. FO and inflammation appear to be part of (dynamic) clusters of risk factors, including malnutrition and hyponatremia. Technology-guided fluid management of the often vulnerable dialysis patient with FO and inflammation cannot yet be based on evidence from randomized controlled trials, in which these specific patients were in general not included. In the absence of those trials, treatment should be based on identifying actionable causes of inflammation and on the judicious removal of excess volume based on frequent clinical reassessment.

Novel Insights into the Pathogenesis and Prevention of Intradialytic Hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD) and associated with adverse outcomes, especially when a nadir definition (systolic blood pressure <90 mm Hg) is used. The pathogenesis of IDH is directly linked to the discontinuous nature of the HD treatment, in combination with patient-related factors such as age, diabetes mellitus and cardiac failure. SUMMARY: Although the decline in blood volume due to removal of fluid by ultrafiltration is the prime mover, thermally induced reflex vasodilation compromises the haemodynamic response to hypovolemia. Recent studies have stressed the relevance of changes in tissue perfusion during HD, which may translate in long-term organ damage. Monitoring changes in tissue perfusion, for which emerging evidence becomes available, appears to have great promise in the fine-tuning of the dialysis procedure. Key Messages: While it is unlikely that IDH can be completely prevented, reduction in inter-dialytic weight gain, prevention of an increase in core temperature by adjusting the dialysate temperature and more frequent or prolonged dialysis treatment remain cornerstones in providing a more comfortable and safe treatment.

Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased cardiovascular disease mortality risk. It is, however, less clear at what point in the course from normal kidney function to CKD the association with cardiovascular disease appears. Studying the associations of estimated glomerular filtration rate (eGFR) and albuminuria with biomarkers of (subclinical) cardiac injury in a population without substantial CKD may clarify this issue. METHODS: We examined the cross-sectional associations of eGFR and urinary albumin excretion (UAE) with high-sensitivity cardiac troponin (hs-cTn) T, hs-cTnI, and N-terminal probrain natriuretic-peptide (NT-proBNP) in 3103 individuals from a population-based diabetes-enriched cohort study. RESULTS: After adjustment for potential confounders, eGFR and UAE were associated with these biomarkers of cardiac injury, even at levels that do not fulfill the CKD criteria. For example, eGFR 60-<90 mL · min-1 ·(1.73 m2)-1 [vs ≥90 mL · min-1 · (1.73 m2)-1] was associated with a [ratio (95% CI)] 1.21 (1.17-1.26), 1.14 (1.07-1.20), and 1.19 (1.12-1.27) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. The association of eGFR with hs-cTnT was statistically significantly stronger than that with hs-cTnI. In addition, UAE 15-<30 mg/24 h (vs <15 mg/24 h) was associated with a 1.04 (0.98-1.10), 1.08 (1.00-1.18), and 1.07 (0.96-1.18) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. CONCLUSIONS: eGFR and albuminuria were already associated with biomarkers of (subclinical) cardiac injury at levels that do not fulfill the CKD criteria. Although reduced renal elimination may partly underlie the associations of eGFR, these findings support the concept that eGFR and albuminuria are, over their entire range, associated with cardiac injury.

Estimated GFR, Albuminuria, and Cognitive Performance: The Maastricht Study.

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. STUDY DESIGN: Cross-sectional analyses of a prospective population-based cohort study. SETTING & PARTICIPANTS: 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). PREDICTOR: eGFR and urinary albumin excretion (UAE). OUTCOMES: Memory function, information processing speed, and executive function. MEASUREMENTS: Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). RESULTS: UAE was <15mg/24 h in 2,439 (81.7%) participants, 15 to <30 mg/24 h in 309 (10.3%), and ≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (ß [SD difference] = -0.148; 95% CI, -0.263 to -0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction < 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFRcr-cys), was 88.4±14.6 mL/min/1.73m2. eGFRcr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFRcr-cys was associated with cognitive performance in older individuals. LIMITATIONS: Cross-sectional design, which limited causal inferences. CONCLUSIONS: In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFRcr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.

Capillary Rarefaction Associates with Albuminuria: The Maastricht Study.

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.

Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration.

BACKGROUND: Protein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced glycation end products (AGEs) associate with cardiovascular disease in dialysis. Intensive haemodialysis (HD) may have significant clinical benefits. The aim of this study was to evaluate the acute effects of conventional and extended HD and haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR) of PBUT, dicarbonyl stress compounds and AGEs. METHODS: Thirteen stable conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound AGEs [N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were determined. RESULTS: Compared with HD4, HDF4 resulted in increased RR of total and/or free fractions of IAA and IS as well as increased RR of free CML and CEL. HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared with HD8, HDF8 only significantly increased RR of total and free IAA and free PCS, as well as RR of free CEL. CONCLUSIONS: Dialysis time extension (HD8 and HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was superior to HD8 for only a few compounds.

Body composition in dialysis patients: a functional assessment of bioimpedance using different prediction models.

OBJECTIVES: The assessment of body composition (BC) in dialysis patients is of clinical importance given its role in the diagnosis of malnutrition and sarcopenia. Bioimpedance techniques routinely express BC as a 2-compartment (2-C) model distinguishing fat mass (FM) and fat-free mass (FFM), which may be influenced by the hydration of adipose tissue and fluid overload (OH). Recently, the BC monitor was introduced which applies a 3-compartment (3-C) model, distinguishing OH, adipose tissue mass, and lean tissue mass. The aim of this study was to compare BC between the 2-C and 3-C models and assess their relation with markers of functional performance (handgrip strength [HGS] and 4-m walking test), as well as with biochemical markers of nutrition. METHODS: Forty-seven dialysis patients (30 males and 17 females) (35 hemodialysis, 12 peritoneal dialysis) with a mean age of 64.8 ± 16.5 years were studied. 3-C BC was assessed by BC monitor, whereas the obtained resistivity values were used to calculate FM and FFM according to the Xitron Hydra 4200 formulas, which are based on a 2-C model. RESULTS: FFM (3-C) was 0.99 kg (95% confidence interval [CI], 0.27 to 1.71, P = .008) higher than FFM (2-C). FM (3-C) was 2.43 kg (95% CI, 1.70-3.15, P < .001) lower than FM (2-C). OH was 1.4 ± 1.8 L. OH correlated significantly with ΔFFM (FFM 3-C - FFM 2-C) (r = 0.361; P < .05) and ΔFM (FM 3-C - FM 2-C) (r = 0.387; P = .009). HGS correlated significantly with FFM (2-C) (r = 0.713; P < .001), FFM (3-C) (r = 0.711; P < .001), body cell mass (2-C) (r = 0.733; P < .001), and body cell mass (3-C) (r = 0.767; P < .001). Both physical activity (r = 0.456; P = .004) and HGS (r = 0.488; P = .002), but not BC, were significantly related to walking speed. CONCLUSIONS: Significant differences between 2-C and 3-C models were observed, which are partly explained by the presence of OH. OH, which was related to ΔFFM and ΔFM of the 2-C and 3-C models, is therefore an important parameter for the differences in estimation of BC parameters of the 2-C and 3-C models. Both FFM (3-C) and FFM (2-C) were significantly related to HGS. Bioimpedance, HGS, and the 4-m walking test may all be valuable tools in the multidimensional nutritional assessment of both hemodialysis and peritoneal dialysis patients.

Acute hemodynamic response and uremic toxin removal in conventional and extended hemodialysis and hemodiafiltration: a randomized crossover study.

BACKGROUND: Intensive hemodialysis (HD) may have significant benefits. Recently, the role of extended hemodiafiltration (HDF) has gained interest. The aim of this study was to evaluate the acute effects of extended HD and HDF on hemodynamic response and solute removal. STUDY DESIGN: Randomized crossover trial. SETTINGS & PARTICIPANTS: Stable patients with end-stage renal disease undergoing conventional HD. INTERVENTION: 13 patients randomly completed a single study of 4-hour HD (HD4), 4-hour HDF (HDF4), 8-hour HD (HD8), and 8-hour HDF (HDF8), with a 2-week interval between study sessions. Between study sessions, patients received routine conventional HD treatments. OUTCOMES: Acute hemodynamic effects and uremic toxin clearance. MEASUREMENTS: Blood pressure and heart rate, pulse wave analysis, cardiac output, and microvascular density by sublingual capillaroscopy, as well as relative blood volume and thermal variables, were measured. Clearance and removal of uremic toxins also were studied. RESULTS: Long treatments showed more stability of peripheral systolic blood pressure (change during HD4, -21.7±15.6 mm Hg; during HDF4, -23.3±20.8 mm Hg; during HD8, -6.7±15.2 mm Hg [P=0.04 vs. HD4; P=0.08 vs. HDF4]; and during HDF8, -0.5±14.4 mm Hg [P=0.004 vs. HD4; P=0.008 vs. HDF4]). A similar observation was found for peripheral diastolic and central blood pressures. Cardiac output remained more stable in extended sessions (change during HD4, -1.4±1.5 L/min; during HDF4, -1.6±1.0 L/min; during HD8, -0.4±0.9 L/min [P=0.02 vs. HDF4]; and during HDF8, -0.5±0.8 L/min [P=0.06 vs. HD4; P=0.03 vs. HDF4), in line with the decreased relative blood volume slope in long dialysis. No differences in microvascular density were found. Energy transfer rates were comparable (HD4, 13.3±4.7 W; HDF4, 16.2±5.6 W; HD8, 14.2±6.0 W; and HDF8, 14.5±4.3 W). Small-molecule and phosphate removal were superior during long treatments. ß2-Microglobulin and fibroblast growth factor 23 (FGF-23) reduction ratios were highest in HDF8. LIMITATIONS: Small sample size, only acute effects were studied. CONCLUSIONS: Treatment time, and not modality, was the determinant for the hemodynamic response. HDF significantly improved removal of middle molecules, with superior results in extended HDF.

The Biobank of Nephrological Diseases in the Netherlands cohort: the String of Pearls Initiative collaboration on chronic kidney disease in the university medical centers in the Netherlands.

Despite advances in preventive therapy, prognosis in chronic kidney disease (CKD) is still grim. Clinical cohorts of CKD patients provide a strategic resource to identify factors that drive progression in the context of clinical care and to provide a basis for improvement of outcome. The combination with biobanking, moreover, provides a resource for fundamental and translational studies. In 2007, the Dutch government initiated and funded the String of Pearls Initiative (PSI), a strategic effort to establish infrastructure for disease-based biobanking in the University Medical Centres (UMCs) in the Netherlands, in a 4-year start-up period. CKD was among the conditions selected for biobanking, and this resulted in the establishment of the Biobank of Nephrological Diseases-NL (BIND-NL) cohort. Patients with CKD Stages 1-4 are eligible. The data architecture is designed to reflect routine care, with specific issues added for enrichment, e.g. questionnaires. Thus, the collected clinical and biochemical data are those required by prevailing guidelines for routine nephrology care, with a minimal dataset for all patients, and diagnosis-specific data for the diagnostic categories of primary and secondary glomerular disorders and adult dominant polycystic kidney disease, respectively. The dataset is supplemented by a biobank, containing serum, plasma, urine and DNA. The cohort will be longitudinally monitored, with yearly follow-up for clinical outcome. Future linking of the data to those from the national registries for renal replacement therapy is foreseen to follow the patients' lifeline throughout the different phases of renal disease and different treatment modalities. In the design of the data architecture, care was taken to ensure future exchangeability of data with other CKD cohorts by applying the data harmonization format of the Renal DataSHaPER, with a dataset based upon standardized indicator sets to facilitate collaboration with other CKD cohorts. Enrolment started in 2010, and over 2200 eligible patients have been enrolled in the different UMCs. Follow-up of enrolled patients has started, and enrolment will continue at a slower rate. The aggregation and standardization of clinical data and biosamples from large numbers of CKD patients will be a strategic resource not only for clinical and translational research, but also by its basis in routine clinical care for clinical governance and quality improvement projects.

Vascular access vulnerability in intensive hemodialysis: a significant Achilles' heel?

BACKGROUND: Frequent hemodialysis (HD) may be associated with an increased risk of vascular access complications. Studies addressing vascular access outcomes in frequent HD show conflicting results. METHODS: We searched Medline for trials looking at vascular access outcomes in frequent HD. RESULTS: Nineteen studies met the inclusion criteria; only studies with a control group were included for analysis (n = 15). The vascular access event rate was higher in intensive HD as compared to conventional HD (difference of 6.7 events per 100 patient-years, p = 0.009). Overall event rates were not significantly different between conventional and intensive HD when stratified for access type, but were notably higher in the arteriovenous grafts and catheter group as compared to the arteriovenous fistula (AVF) group. CONCLUSION: Intensive HD is associated with an increased risk of vascular access complications. Overall reported event rates were lower in the AVF group. Further controlled studies should investigate whether a 'fistula first' strategy may be recommended also for intensive HD.

Effects of ultrapure hemodialysis and low molecular weight heparin on the endothelial surface layer.

BACKGROUND: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. METHODS: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B. Mean platelet volume (MPV) and platelet large cell ratio (P-LCR) were also measured. RESULTS: Syndecan-1 increased significantly 30 min after LMWH administration. sP-Selectin increased 120 min after HD start, and MPV and P-LCR decreased significantly during HD. No significant changes of PBR, sE-Selectin, sICAM-1, or sVCAM-1 were perceived. CONCLUSIONS: HD caused a significant increase in Syndecan-1 without a change in PBR. The administration of LMWH appeared to precede the rise in Syndecan-1.

Out of control: accelerated aging in uremia.

Next to a high morbidity, patients with end-stage renal failure (ESRD) suffer from a complex spectrum of clinical manifestations. Both the phenotype of patients with ESRD as well as the pathophysiology of uremia show interesting parallels with the general aging process. Phenotypically, patients with ESRD have an increased susceptibility for both cardiovascular as well as infectious disease and show a reduction in functional capacity as well as muscular mass (sarcopenia), translating into a high prevalence of frailty also in younger patients. Pathophysiologically, the immune dysfunction, telomere attrition and the presence of low-grade inflammation in uremic patients also show parallels with the aging process. System models of aging, such as the homeodynamic model and reliability theory of Gavrilov may also have relevance for ESRD. The reduction in the redundancy of compensatory mechanisms and the multisystem impairment in ESRD explain the rapid loss of homeodynamic/homeostatic balance and the increased susceptibility to external stressors in these patients. System theories may also explain the relative lack of success of interventions focusing on single aspects of renal disease. The concept of accelerated aging, which also shares similarities with other organ diseases, may be of relevance both for a better understanding of the uremic process, as well as for the design of multidimensional interventions in ESRD patients, including an important role for early rehabilitation. Research into processes akin to both aging and uremia may result in novel therapeutic approaches.

Circadian variations in body temperature during dialysis.

BACKGROUND: Thermal changes during dialysis strongly influence intra-dialytic hemodynamics. The mechanisms behind the increase in body temperature during hemodialysis (HD) are still not completely understood. The objective of this retrospective observational cohort study is to assess the effect of circadian variation on body temperature changes during HD by comparing results in patients treated on different treatment shifts. METHODS: Data from the Renal Research Institute, New York, clinical database encompassing patients treated in six states in the USA were used. Data from January and August 2008 were used for analysis. Body temperature changes during HD were categorized by dialysis shifts. Patients with morning shifts (n = 1064), afternoon shifts (n = 730) and evening shifts (n = 210) were compared. RESULTS: Pre-dialysis body temperatures were significantly different among the different shifts [morning, 36.41 (95% confidence interval: 36.39-36.43°C), afternoon, 36.47 (36.45-36.49°C), evening, 36.67 (36.64-36.70°C), P < 0.001]. In August, but not in January, intra-dialytic increases in body temperature were significantly different between patients treated during morning [0.07 (0.058-0.082°C)], afternoon [0.03 (0.016-0.044°C)] and evening shifts [-0.01 (-0.032 to 0.012°C); P < 0.001 analysis of variance], although in January, treatment shift was a significant predictor of the intra-dialytic increase in body temperature. The intra-dialytic change in body temperature was related not only to the pre-dialysis body temperature (r(2) = 0.31; P < 0.001) but also to microbiological dialysate quality, treatment time and dialysate temperature. The intra-dialytic change in blood pressure (BP) was significantly related to changes in intra-dialytic body temperature irrespective of the study month. CONCLUSIONS: Both pre-dialytic body temperature as well as changes in body temperature are significantly related to the timing of the dialysis shifts, in phase with the circadian body temperature rhythm. Due to the relationship between body temperature changes and changes in intra-dialytic BP, these findings might be of additional relevance in the pathogenesis of intra-dialytic hypotension.

Prospective study on clinical effects of renal replacement therapy in treatment-resistant congestive heart failure.

BACKGROUND/AIMS: Clinical outcome in cardiorenal syndrome (CRS) Type 2 and treatment with dialysis. METHODS: Prospective observational non-randomized study. RESULTS: Twenty-three patients were included, mean age 66±21 years. Twelve (52%) patients were treated with peritoneal dialysis (PD) and 11 (48%) with intermittent haemodialysis (IHD). Median survival time after start of dialysis was 16 months. Hospitalizations for cardiovascular causes were reduced (1.4±0.6 pre-dialysis versus 0.4±0.6 days/patient/month post-dialysis, P=0.000), without significant changes in hospitalization for all causes (1.8±1.6 versus 2.1±2.9 days/patient/month). New York Heart Association (NYHA) class (3.8±0.4 at start versus 2.4±0.7 after 4 months, P=0.000, versus 2.7±0.9 after 8 months, P=0.001) and quality of life tended to improve (63±21 at start, versus 41±20 after 4 months, versus 51±25 after 8 months; P=0.056). Left ventricular ejection fraction did not change. The number of technical complications associated with dialysis therapy was relatively high in this population. CONCLUSIONS: After starting dialysis for CRS, hospitalizations for cardiovascular causes were reduced, but not hospitalizations for all causes. Functional NYHA class improved and quality of life tended to improve, without evidence for a change in cardiac function. In this small study, no differences between IHD and PD were observed.

'Time and time again': oscillatory and longitudinal time patterns in dialysis patients.

Oscillatory and longitudinal time patterns play a major role in human physiology. In chronic hemodialysis patients, abnormalities in both time patterns have been observed, while time patterns can also influence the response of patients to the treatment. Abnormal oscillatory patterns have been observed for ultradian rhythms (cycle time <20 h), such as an impaired heart rate variability and circadian rhythms, as reflected by reduced day-night blood pressure differences. Conversely, the circadian rhythm of body temperature may influence the hemodynamic tolerance to the dialysis treatment. With regard to infradian (cycle time >28 h) rhythms, large seasonal differences in mortality, but also in blood pressure and interdialytic weight gain, have been observed in dialysis patients. The most important longitudinal pattern is the general reduction of life span in dialysis patients. One explanation of this phenomenon relates to the concept of accelerated aging in dialysis patients, for which there are various supportive arguments. From a phenomenological point of view, this concept translates into the high prevalence of frailty, even in young dialysis patients. A multidimensional approach appears necessary to adequately address this problem. In this review, the relevance of disturbed time patterns in dialysis patients is discussed. The changes may reflect an impairment or reduction in homeostatic/homeodynamic control in dialysis patients and also may have important prognostic and therapeutic implications.

Renal replacement therapy in geriatric end-stage renal disease patients: a clinical approach.

The number of geriatric patients on dialysis is increasing. This is due to demographic factors, a wider acceptance of elderly patients on dialysis, and an earlier start of dialysis in this patient group. Recent studies have questioned the effect of dialysis on quality of life in elderly patients with severe comorbidity and showed limited survival in this specific patient group. Therefore, the decision whether or not to start dialysis may be a difficult one for both the clinician and patient. Risk scores can be of help in facilitating shared decision making, but not as a tool to withhold dialysis. However, in the elderly patient with severe comorbidity, conservative care can sometimes be a reasonable alternative to dialysis. In the process of shared decision making, a balance should be pursued between life expectancy and quality of life. If the decision to initiate dialysis is taken, choices have to be made regarding dialysis modality and treatment prescription. If adequate support is provided, assisted peritoneal dialysis can be an acceptable alternative to hemodialysis. Care for the elderly with end-stage renal disease should be undertaken by a multidisciplinary team with special dedication to a multidimensional approach in this population.

Inflammation, overhydration and cardiac biomarkers in haemodialysis patients: a longitudinal study.

BACKGROUND: Inflammation, overhydration and elevated cardiac biomarkers are related to outcome in haemodialysis (HD) patients. Here, we explored the relationship between the body composition (BC), inflammation and cardiac biomarker concentrations in HD patients longitudinally. METHODS: A total of 44 HD patients were followed for 6 months. BC was assessed by multifrequency bioimpedance (BIA). Serum concentrations of cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were assessed at 2 monthly intervals. The longitudinal data analysis was conducted with a marginal model. RESULTS: During the follow-up, the parameters describing the BC were highly predictive of both BNP and NT-proBNP and independent of gender, time, hsCRP and cTnT concentrations. The intracellular water (ICW)/body weight (BW) ratio (reflecting malnutrition) exerted a negative effect, whereas the extracellular water (ECW)/BW ratio (reflecting overhydration) had a positive effect on BNP and NT-proBNP concentrations. HsCRP and cTnT concentrations were significantly associated with each other. Furthermore, NT-proBNP concentrations were predictive of cTnT and hsCRP concentrations. CONCLUSIONS: In the present study, we find a significant relation between BIA-derived BC parameters and natriuretic peptide concentrations. This relationship was independent of the cardiac history of the patient and suggests that the natriuretic peptide levels are to some degree modifiable by changing a patient's fluid distribution. Moreover, cTnT, BNP, NT-proBNP and hsCRP were significantly related, showing a complex relation between overhydration, malnutrition, inflammation and cardiac biomarkers in dialysis patients.