Amino Acid Homeostasis and Fatigue in Chronic Hemodialysis Patients.

Patients dependent on chronic hemodialysis treatment are prone to malnutrition, at least in part due to insufficient nutrient intake, metabolic derangements, and chronic inflammation. Losses of amino acids during hemodialysis may be an important additional contributor. In this study, we assessed changes in plasma amino acid concentrations during hemodialysis, quantified intradialytic amino acid losses, and investigated whether plasma amino acid concentrations and amino acid losses by hemodialysis and urinary excretion are associated with fatigue. The study included a total of 59 hemodialysis patients (65 ± 15 years, 63% male) and 33 healthy kidney donors as controls (54 ± 10 years, 45% male). Total plasma essential amino acid concentration before hemodialysis was lower in hemodialysis patients compared with controls (p = 0.006), while total non-essential amino acid concentration did not differ. Daily amino acid losses were 4.0 ± 1.3 g/24 h for hemodialysis patients and 0.6 ± 0.3 g/24 h for controls. Expressed as proportion of protein intake, daily amino acid losses of hemodialysis patients were 6.7 ± 2.4% of the total protein intake, compared to 0.7 ± 0.3% for controls (p < 0.001). Multivariable regression analyses demonstrated that hemodialysis efficacy (Kt/V) was the primary determinant of amino acid losses (Std. ß = 0.51; p < 0.001). In logistic regression analyses, higher plasma proline concentrations were associated with higher odds of severe fatigue (OR (95% CI) per SD increment: 3.0 (1.3; 9.3); p = 0.03), while higher taurine concentrations were associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.3 (0.1; 0.7); p = 0.01). Similarly, higher daily taurine losses were also associated with lower odds of severe fatigue (OR (95% CI) per log2 increment: 0.64 (0.42; 0.93); p = 0.03). Lastly, a higher protein intake was associated with lower odds of severe fatigue (OR (95% CI) per SD increment: 0.2 (0.04; 0.5); p = 0.007). Future studies are warranted to investigate the mechanisms underlying these associations and investigate the potential of taurine supplementation.

Chronic Dialysis Patients Are Depleted of Creatine: Review and Rationale for Intradialytic Creatine Supplementation.

There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6-1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages.

Complementary Biomarker Assessment of Components Absorbed from Diet and Creatinine Excretion Rate Reflecting Muscle Mass in Dialysis Patients.

To prevent protein energy malnutrition (PEM) and accumulation of waste products, dialysis patients require diet adjustments. Dietary intake assessed by self-reported intakes often provides biased information and standard 24-h urinary excretion is inapplicable in dialysis patients. We aimed to assess dietary intake via a complementary, less biased biomarker method, and to compare this to dietary diaries. Additionally, we investigated the prospective association of creatinine excretion rate (CER) reflecting muscle mass with mortality. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h excretion of protein, sodium, potassium, phosphate and creatinine in 42 chronic dialysis patients and compared with protein, sodium, potassium, and phosphate intake assessed by 5-day dietary diaries. Cox regression analyses were employed to investigate associations of CER with mortality. Mean age was 64 ± 13 years and 52% were male. Complementary biomarker assessed (CBA) and dietary assessed (DA) protein intake were significantly correlated (r = 0.610; p < 0.001), but there was a constant bias, as dietary diaries overestimated protein intake in most patients. Correlations were found between CBA and DA sodium intake (r = 0.297; p = 0.056), potassium intake (r = 0.312; p = 0.047) and phosphate uptake/intake (r = 0.409; p = 0.008). However, Bland-Altman analysis showed significant proportional bias. During a median follow-up of 26.6 (25.3⁻31.5) months, nine dialysis patients (23%) died. CER was independently and inversely associated with survival (HR: 0.59 (0.42⁻0.84); p = 0.003). Excretion measurements may be a more reliable assessment of dietary intake in dialysis patients, as this method is relatively free from biases known to exist for self-reported intakes. CER seems to be a promising tool for monitoring PEM.

Vasopressin release is enhanced by the Hemocontrol biofeedback system and could contribute to better haemodynamic stability during haemodialysis.

BACKGROUND: Haemodialysis with the Hemocontrol biofeedback system (HHD) is associated with improved haemodynamic stability compared with standard haemodialysis (HD) (SHD). Although the beneficial effect of HHD on haemodynamic stability is generally explained by its effect on blood volume, we questioned whether additional factors could play a role. Since HHD is associated with higher initial dialysate sodium concentrations and ultrafiltration (UF) rate, we studied whether the beneficial effect of HHD on haemodynamic stability may be explained by an increased release of the vasoconstrictor arginine vasopressin (AVP). METHODS: Fifteen chronic dialysis patients underwent SHD and HHD in random order. All other treatment factors were identical and patients served as their own control. Plasma levels of AVP were measured pre-dialysis, at 30 and 60 min intra-dialysis and, next, hourly until completion of the dialysis session. RESULTS: Plasma AVP levels did not change significantly during SHD, whereas AVP levels rose significantly within 30 min after the start of HHD (P < 0.01). AVP levels were significantly higher at 30 and 60 min of HHD in comparison with SHD (P < 0.05). Dialysis hypotension occurred significantly less frequent during HHD than during SHD (P < 0.05). CONCLUSIONS: HHD is associated with higher initial AVP levels compared with SHD. The enhanced release of the vasoconstrictor AVP with HHD could contribute to the lower frequency of dialysis hypotension by facilitating fluid removal during the first part of the dialysis session, permitting lower UF rates during the second half of the dialysis session.

Exploration of the difference in incidence of renal replacement therapy between Flanders and the Netherlands--investigation of explanatory variables.

AIM: This study investigates the difference in the incidence of renal replacement therapy (RRT) between Flanders and the Netherlands and possible explanations for this difference. METHODS: End-stage renal disease incidence data were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). Additional sources were the National Institute of Statistics (NIS), the Central Bureau of Statistics (CBS), the Organisation for Economic Cooperation and Development (OECD) health data and the WHO Health For All database (WHO-HFA). RESULTS: There is remarkable difference in incidence rate of RRT between Flanders and the Netherlands, with a higher rate in Flanders. This difference is already present in patients aged 45-64 years and increases with age, being >2-fold higher in subjects of ≥ 75 years. With respect to the renal diagnoses leading to need for RRT, a higher share of especially diabetes mellitus type 2 and renovascular disease was observed in Flanders. Remarkably, the difference in incidence rate of RRT is not associated with a difference in survival on RRT, not even in the elderly, arguing against a restricted access to RRT in the Netherlands. In the general population, the expected number of healthy life years at birth is lower in Belgium than in the Netherlands, and in Belgium, the hospital discharge rates for diabetes, acute myocardial infarction and cerebrovascular accident and the number of coronary bypass procedures and percutaneous coronary interventions per capitum is higher, as is the prevalence of obesity. CONCLUSION: Our data do not support the assumption that the differences in RRT incidence in the elderly between Flanders and the Netherlands are due to a more restricted access to RRT in the Netherlands but may be due to differences in underlying comorbidity and life style between the two populations.