Can Overnutrition Lead to Wasting?—The Paradox of Diabetes Mellitus in End-Stage Renal Disease Treated with Maintenance Hemodialysis

Background: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). Methods: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. Results: DM patients had lower albumin (3.93 (3.61–4.20) vs. 4.10 (3.80–4.30) g/dL, p < 0.01), total cholesterol (158 (133–196) vs. 180 (148–206) mg/dL, p < 0.01), and creatinine (6.34 (5.08–7.33) vs. 7.12 (5.70–8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0–15.0) vs. 11.0 (9.0–13.0) points, p < 0.001), BMI (27.9 (24.4–31.8) vs. 25.6 (22.9–28.8) kg/m2, p < 0.001), fat tissue index (15.0 (11.4–19.6) vs. 12.8 (9.6–16.0) %, p < 0.001), and overhydration (2.1 (1.2–4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality—both all-cause and cardiovascular—were observed in DM patients. Conclusions: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited.Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW.Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures.Results: Muscle indices as per US metrics indicated significance (p &lt; 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p &lt; 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p &lt; 0.001), along with lower malnutrition–inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision.Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

Intradialytic nutrition and quality of life in Chilean older patients in hemodialysis with protein-energy wasting

Purpose The study assessed the impact of intradialytic oral nutritional supplementation on the quality of life in patients receiving hemodialysis and diagnosed with protein energy wasting. Methods A pre-test post-test quasi-experimental study was conducted before and after 3 months of intradialytic oral nutritional supplementation on 109 older hemodialysis patients. We measured before and after 3 months of intradialytic oral nutritional supplementation, the quality of life score, the burden of kidney disease, three quality of life scales and the mental and physical health status using KDQoL-SF™ 1.3, body composition and biochemical parameters of nutritional condition. Results The mean age of the patients was 69.4 ± 3.4 years, 59% were male, and the time on dialysis was 63.5 ± 52.6 months. Comparing the baseline with month 3 of intradialytic oral nutritional supplementation, we observed to better quality of life. In contrast to malnutrition, score, specifically increased significantly score of symptoms/problems list related to hemodialysis, sexual function, social and cognitive function, sleep, pain, energy/fatigue and general state of health. Significant changes were also found in nutritional status, energy intake and body composition indicators. After 3 months of intradialytic oral nutritional supplementation, we observed a nutritional status recovery in one or more indicators in 92% of the patients. Conclusion Our findings indicate that 3 months of intradialysis oral nutritional supplementation improves the components of physical and mental quality of life and nutritional status in older patients receiving hemodialysis diagnosed with loss of protein energy. These results are relevant to improve the experience of patients with protein energy loss receiving hemodialysis.

Ernährung

Etwa 10–15 % der Weltbevölkerung leiden an einer chronischen Nierenerkrankung (CKD), die mit einem irreversiblen Verlust der Nierenfunktion einhergeht. Eine globale Metaanalyse brachte eine Prävalenz eines Protein-Energy Wasting (PEW) bei 11–54 % der prädialytischen CKD-Patienten (Stadium 3–5) hervor. In der Gruppe der dialysierten Patienten waren 28–54 % betroffen. Auch wenn die Spannweite der Prävalenzen aufgrund unterschiedlicher Bewertungskriterien der Studien sehr groß ist, kann eine steigende PEW-Prävalenz mit zunehmendem CKD-Stadium bestätigt werden 1.

Serum Osteoprotegerin Is an Independent Marker of Metabolic Complications in Non-DialysisDependent Chronic Kidney Disease Patients

Background: Osteoprotegerin (OPG) belongs to the tumour necrosis factor superfamily and is known to accelerate endothelial dysfunction and vascular calcification. OPG concentrations are elevated in patients with chronic kidney disease. The aim of this study was to investigate the association between OPG levels and frequent complications of chronic kidney disease (CKD) such as anaemia, protein energy wasting (PEW), inflammation, overhydration, hyperglycaemia and hypertension. Methods: One hundred non-dialysis-dependent men with CKD stage 3–5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure overhydration, fat amount and lean body mass. We also measured the serum concentrations of haemoglobin, albumin, total cholesterol, C-reactive protein (CRP), fibrinogen and glycated haemoglobin (HgbA1c), as well as blood pressure. Results: We observed a significant, positive correlation between OPG and age, serum creatinine, CRP, fibrinogen, HgbA1c concentrations, systolic blood pressure and overhydration. Negative correlations were observed between OPG and glomerular filtration rate (eGFR), serum albumin concentrations and serum haemoglobin level. Logistic regression models revealed that OPG is an independent marker of metabolic complications such as anaemia, PEW, inflammation and poor renal prognosis (including overhydration, uncontrolled diabetes and hypertension) in the studied population. Conclusion: Our results suggest that OPG can be an independent marker of PEW, inflammation and vascular metabolic disturbances in patients with chronic kidney disease.