Association between objectively measured protein intake and muscle status, health-related quality of life, and mortality in hemodialysis patients.

BACKGROUND: Protein intake is known to be associated with muscle mass, health-related quality of life (HRQoL), and mortality in patients with stage 5 chronic kidney disease undergoing dialysis. However, most studies evaluated protein intake based on 24 h dietary recall or food frequency questionnaire, and these methods are prone to bias. Therefore, this study aimed to evaluate the association of objectively measured protein intake with muscle mass and strength, HRQoL, and mortality. METHODS: Dietary protein intake was calculated based on the combined (urinary and dialysate) urea excretion rate according to the Maroni formula and indexed to body weight. Muscle mass was calculated based on the combined dialysate and urinary creatinine excretion rate, and muscle strength was assessed by handgrip strength. HRQoL was based on the Short Form 36. Linear and Cox regression were used for the analyses. RESULTS: We included 59 hemodialysis patients (mean age 65 ± 15 years, 37% female, median hemodialysis vintage 15 [6-39] months). Mean protein intake was 0.82 ± 0.23 g/kg/day, and 76% had a low protein intake (<1.0 g/kg/day). Higher protein intake was independently associated with higher muscle mass (Standardized beta (St. ß) [95% confidence interval (95%CI) = 0.56 [0.34 to 0.78]) and higher scores on the physical functioning domain of HRQoL (St. ß [95%CI] = 0.49 [0.25 to 0.73]), but not with muscle strength (St. ß [95%CI] = 0.17 [-0.10 to 0.43]). During a median follow-up of 21.6 [8.6-36.6] months, 16 (27.1%) patients died. Higher protein intake was associated with lower mortality risk (hazard ratio [95%CI] = 0.34 [0.16-0.73]). This association remained significant after adjustment for potential confounders. CONCLUSIONS: Protein intake is independently associated with muscle mass, physical functioning domain of HRQOL, and mortality. Clinicians and dietitians should closely monitor the protein intake of hemodialysis patients.

The Impact of Combined Nutrition and Exercise Interventions in Patients with Chronic Kidney Disease.

Combined nutrition and exercise interventions potentially improve protein-energy wasting/malnutrition-related outcomes in patients with chronic kidney disease (CKD). The aim was to systematically review the effect of combined interventions on nutritional status, muscle strength, physical performance and QoL. MEDLINE, Cochrane, Embase, Web of Science and Google Scholar were searched for studies up to the date of July 2023. Methodological quality was appraised with the Cochrane risk-of-bias tool. Ten randomized controlled trials (nine publications) were included (334 patients). No differences were observed in body mass index, lean body mass or leg strength. An improvement was found in the six-minute walk test (6-MWT) (n = 3, MD 27.2, 95%CI [7 to 48], p = 0.008), but not in the timed up-and-go test. No effect was found on QoL. A positive impact on 6-MWT was observed, but no improvements were detected in nutritional status, muscle strength or QoL. Concerns about reliability and generalizability arise due to limited statistical power and study heterogeneity of the studies included.

Effects of salt and protein intake on polyuria in V2RA-treated ADPKD patients.

BACKGROUND: The only treatment proven to be renoprotective in autosomal dominant polycystic kidney disease (ADPKD) is a vasopressin V2-receptor antagonist (V2RA). However, aquaresis-associated side effects limit tolerability. We investigated whether salt and/or protein intake influences urine volume and related endpoints in V2RA-treated ADPKD patients. METHODS: In this randomized, controlled, double-blind, crossover trial, ADPKD patients treated with maximally tolerated dose of a V2RA were included. While on a low salt and low protein diet, patients were given additional salt and protein to mimic regular intake, which was subsequently replaced by placebo in random order during four 2-week periods. Primary endpoint was change in 24-h urine volume. Secondary endpoints were change in quality of life, measured glomerular filtration rate (mGFR), blood pressure and copeptin level. RESULTS: Twelve patients (49 ± 8 years, 25.0% male) were included. Baseline salt and protein intake were 10.8 ± 1.3 g/24-h and 1.2 ± 0.2 g/kg/24-h, respectively. During the low salt and low protein treatment periods, intake decreased to 5.8 ± 1.6 g/24-h and 0.8 ± 0.1 g/kg/24-h, respectively. Baseline 24-h urine volume (5.9 ± 1.2 L) decreased to 5.2 ± 1.1 L (-11%, P = .004) on low salt and low protein, and to 5.4 ± 0.9 L (-8%, P = .04) on low salt. Reduction in 24-h urine volume was two times greater in patients with lower urine osmolality (-16% vs -7%). Polyuria quality of life scores improved in concordance with changes in urine volume. mGFR decreased during the low salt and low protein, while mean arterial pressure did not change during study periods. Plasma copeptin decreased significantly during low salt and low protein periods. CONCLUSION: Lowering dietary salt and protein intake has a minor effect on urine volume in V2RA-treated ADPKD patients. Reduced intake of osmoles decreased copeptin concentrations and might thus increase the renoprotective effect of a V2RA in ADPKD patients.

Creatinine synthesis rate and muscle strength and self-reported physical health in dialysis patients.

BACKGROUND & AIMS: Urinary creatinine excretion reflecting endogenous creatinine synthesis rate (CSR) is an established measure of muscle mass in the general populations and in patients with chronic kidney disease. There is increasing data to suggest that CSR not only reflects muscle mass, but also muscle function. In dialysis patients, CSR has rarely been studied since it requires dialysate collection. We aimed to study whether CSR is associated with muscle strength, and self-reported physical health in dialysis patients. METHODS: Total daily CSR (dialytic removal plus, if applicable, urinary excretion), handgrip strength, and self-reported physical health according subscales of the Checklist Individual Strength and the Short Form-36 were assessed in 50 dialysis patients. Associations of CSR, indexed to body surface area, with handgrip strength and self-reported physical health were studied using multivariable linear regression models. RESULTS: Median age was 69 [interquartile range 60-78] years. Mean CSR was higher in men than in women (9.5 ± 3.3 mmol/24 h versus 6.8 ± 1.9 mmol/24 h respectively, P = 0.007). Age, BMI, and plasma albumin were positively associated with CSR. CSR was positively associated with handgrip strength (adjusted (a-) ß: 0.44 [95% CI: 0.18 to 0.71), physical functioning (a-ß: 0.54 [95% CI: 0.19 to 0.88]), social functioning (a-ß: 0.43 [95%CI 0.08 to 0.76]), and inversely with physical inactivity (adjusted ß: -0.69 [95% CI: -1.00 to -0.38), fatigue (adjusted ß: -0.61 [95% CI: -0.93 to -0.27]), and role limitation due to physical health (a-ß: 0.39 [95% CI: 0.04 to 0.74]). CONCLUSIONS: In dialysis patients, a greater CSR is associated with higher muscle strength, better physical and social functioning, and physical activity, and with less fatigue, and role limitation due to physical health. Thus, CSR reflects muscle function, self-reported physical health and social functioning in dialysis patients.

Tryptophan Intake and Tryptophan Losses in Hemodialysis Patients: A Balance Study.

Tryptophan depletion is common in hemodialysis patients. The cause of this depletion remains largely unknown, but reduced nutritional tryptophan intake, losses during dialysis or an increased catabolism due to an inflammatory state are likely contributors. Currently, little is known about tryptophan homeostasis in hemodialysis patients. We assessed dietary tryptophan intake, measured plasma tryptophan during dialysis, and measured the combined urinary and dialysate excretion of tryptophan in 40 hemodialysis patients (66 ± 15 years and 68% male). Patients had low tryptophan concentrations (27 ± 9 µmol/L) before dialysis. Mean dietary tryptophan intake was 4454 ± 1149 µmol/24 h. Mean urinary tryptophan excretion was 15.0 ± 12.3 µmol/24 h, dialysate excretion was 209 ± 67 µmol/24 h and combined excretion was 219 ± 66 µmol/24 h, indicating only 5% of dietary tryptophan intake was excreted. No associations were found between plasma tryptophan concentration and tryptophan intake, plasma kynurenine/tryptophan ratio or inflammatory markers. During dialysis, mean plasma tryptophan concentration increased 16% to 31 ± 8 µmol/L. Intradialytic increase in plasma tryptophan was associated with a lower risk of mortality, independent of age, sex and dialysis vintage (HR: 0.87 [0.76-0.99]; P = 0.04). Tryptophan intake was well above the dietary recommendations and, although tryptophan was removed during dialysis, mean plasma tryptophan increased during dialysis. The cause of this phenomenon is unknown, but it appears to be protective.

The Prevalence of Intradialytic Hypotension in Patients on Conventional Hemodialysis: A Systematic Review with Meta-Analysis.

BACKGROUND: Intradialytic hypotension (IDH) is considered to be a frequent complication of hemodialysis (HD) and is associated with symptom burden, increased incidence of access failure, cardiovascular events, and higher mortality. This systematic literature review aims to analyse studies that investigated the prevalence of IDH. A complicating factor herein is that many different definitions of IDH are used in literature. METHODS: A systematic literature search from databases, Medline, Cinahl, EMBASE, and the Cochrane library to identify studies reporting on the actual prevalence of IDH was conducted. Studies were categorized by the type of definition used for the prevalence of IDH. A meta-analysis of the prevalence of IDH was performed. RESULTS: In a meta-analysis comprising 4 studies including 1,694 patients and 4 studies including 13,189 patients, the prevalence of HD sessions complicated by IDH was 10.1 and 11.6% for the European Best Practice Guideline (EBPG) definition and the Nadir <90 definition, respectively. The proportion of patients with frequent IDH could not reliably be established because of the wide range in cutoff values that were used to identify patients with frequent IDH. There was a large variety in the prevalence of symptoms and interventions. Major risk factors associated with IDH across studies were diabetes, a higher interdialytic weight gain, female gender, and lower body weight. CONCLUSION: Our meta-analysis suggests that the prevalence of IDH is lower than 12% for both the EBPG and the Nadir <90 definition which is much lower than stated in most reviews.

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.

Causes and Consequences of Interdialytic weight gain.

BACKGROUND/AIMS: Higher interdialytic weight gain (IDWG) is associated with higher predialysis blood pressure and increased mortality. IDWG is also increasingly being recognized as an indicator of nutritional status. We studied in detail the associations of various patient factors and nutritional parameters with IDWG. METHODS: We collected data during one week for IDWG and hemodynamic parameters in 138 prevalent adult haemodialysis patients on a thrice-weekly haemodialysis schedule. A multivariate linear regression analysis was employed to identify factors that are associated with IDWG. RESULTS: The mean (±SD) age was 62.5 (±18.2) years, 36% were female, 36% had diuresis, and 23% had diabetes. Patients in the highest IDWG tertile were significantly younger, more frequently male, and had a significantly higher subjective global assessment score (SGA). A higher IDWG as a percentage of body weight (%IDWG) was associated with a younger age, greater height and weight, absence of diuresis, and lower postdialysis plasma sodium levels. The model with these five parameters explained 37% of the variance of %IDWG. Predialysis, intradialysis, and postdialysis diastolic blood pressure was significantly higher in the highest tertile of IDWG. CONCLUSION: The most important associations of %IDWG are age, height, weight, diuresis, and postdialysis sodium. Patients with the highest IDWG have significantly higher diastolic blood pressures.

Nutritional Status in Nocturnal Hemodialysis Patients - A Systematic Review with Meta-Analysis.

BACKGROUND: Hemodialysis patients experience an elevated risk of malnutrition associated with increased morbidity and mortality. Nocturnal hemodialysis (NHD) results in more effective removal of waste products and fluids. Therefore, diet and fluid restrictions are less restricted in NHD patients. However, it is ambiguous whether transition from conventional hemodialysis (CHD) to NHD leads to improved intake and nutritional status. We studied the effect of NHD on protein intake, laboratory indices of nutritional status, and body composition. STUDY DESIGN: Systematic review with meta-analysis. POPULATION: NHD patients. SEARCH STRATEGY: Systematic literature search from databases, Medline, Cinahl, EMBASE and The Cochrane Library, to identify studies reporting on nutritional status post-transition from CHD to NHD. INTERVENTION: Transition from CHD to NHD. OUTCOMES: Albumin, normalized protein catabolic rate (nPCR), dry body weight (DBW), body mass index (BMI), phase angle, protein intake, and energy intake. RESULTS: Systematic literature search revealed 13 studies comprising 282 patients that made the transition from CHD to NHD. Meta-analysis included nine studies in 229 patients. In control group controlled studies (n = 4), serum albumin increased significantly from baseline to 4-6 months in NHD patients compared with patients that remained on CHD (mean difference 1.3 g/l, 95% CI 0.02; 2.58, p = 0.05). In baseline controlled studies, from baseline to 4-6 months of NHD treatment, significant increases were ascertained in serum albumin (mean difference (MD) 1.63 g/l, 95% CI 0.73-2.53, p<0.001); nPCR (MD 0.16 g/kg/day; 95% CI 0.04-0.29, p = 0.01); protein intake (MD 18.9 g, 95% CI 9.7-28.2, p<0.001); and energy intake (MD 183.2 kcal, 95% CI 16.8-349.7, p = 0.03). Homogeneity was rejected only for nPCR (baseline versus 4-6 months). DBW, BMI, and phase angle did not significantly change. Similar results were obtained for comparison between baseline and 8-12 months of NHD treatment. LIMITATIONS: Most studies had moderate sample sizes; some had incomplete dietary records and relatively brief follow-up period. Studies markedly differed with regard to study design. CONCLUSIONS: NHD is associated with significantly higher protein and energy intake as well as increases in serum albumin and nPCR. However, the data on body composition are inconclusive.

Effect of nocturnal haemodialysis on body composition.

BACKGROUND: Haemodialysis patients have a high risk of malnutrition which is associated with increased mortality. Nocturnal haemodialysis (NHD) is associated with a significant increase in protein intake compared with conventional haemodialysis (CHD). It is unclear whether this leads to improved nutritional status. Therefore, we studied whether 1 year of NHD is associated with a change in body composition. METHODS: Whole-body composition using dual-energy X-ray absorptiometry (DEXA) and normalised protein catabolic rate (nPCR) were measured in 11 adult patients before and 1 year after the transition from CHD (12 h dialysis/week) to NHD (28-48 h dialysis/week). Similar measurements were performed in a matched control group of 13 patients who stayed on CHD. Differences between groups were analysed with linear mixed models. RESULTS: At baseline, nPCR, total mass, fat-free mass, and fat mass did not differ significantly between the CHD and NHD groups. nPCR increased in the NHD group (from 0.96 ± 0.23 to 1.12 ± 0.20 g/kg/day; p = 0.027) whereas it was stable in the CHD group (0.93 ± 0.21 at baseline and 0.87 ± 0.09 g/kg/day at 1 year, n.s.). The change in nPCR differed significantly between the two groups (p = 0.027). We observed no significant differences in the course of total mass, fat-free mass, and fat mass during the 1-year observation period between the NHD and CHD groups. CONCLUSIONS: One year of NHD had no significant effect on body composition in comparison with CHD, despite a significantly higher protein intake in patients on NHD.

A difference between day and night: protein intake improves after the transition from conventional to frequent nocturnal home hemodialysis.

BACKGROUND: Malnutrition is an important cause of the excessive morbidity and mortality rate of dialysis patients. Frequent nocturnal home hemodialysis (NHHD) has many benefits compared with conventional thrice-weekly hemodialysis (CHD), due to the virtual absence of dietary restrictions and a much higher overall dialysis efficiency. In this observational study, we investigated whether these benefits of NHHD translate into an improved nutritional intake, with a special emphasis on protein intake. METHODS: We prospectively assessed the effect of the transition of CHD to NHHD on nutritional intake (5-day dietary intake journal), normalized protein catabolic rate, and anthropometric parameters in 15 consecutive patients who started NHHD in our center between 2004 and 2009 and completed at least 8 months of follow-up. Data were collected before the transition from CHD to NHHD and 4 and 8 months after the transition. RESULTS: Protein intake, as measured by both dietary intake journal and normalized protein catabolic rate, increased significantly after the transition from CHD to NHHD. Accordingly, phosphate intake increased significantly; however, serum phosphate levels did not increase, despite negligible phosphate binder use during NHHD. Body mass index and upper arm muscle circumference did not change significantly. CONCLUSION: The transition from CHD to NHHD has a positive effect on nutritional intake, in particular, protein intake. NHHD should be considered in malnourished patients on CHD.