Markers Of Protein-energy Wasting Research Articles

Bioelectrical impedance analysis-derived phase angle as a determinant of protein-energy wasting and frailty in maintenance hemodialysis patients: retrospective cohort study

BackgroundPhase angle (PA), measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in hemodialysis (HD) patients. It remains unclear if the phase angle is associated protein-energy wasting (PEW) or frailty, which are common complication in hemodialysis patients. The aim of this study is to determine whether BIA-derived PA is a marker of PEW or frailty in HD patients.MethodsThis retrospective observational study included 116 adult HD patients (35% female, 64 ± 12 years of age) in a single dialysis center. Patients were classified according to the PA quartiles into four groups; 1) first quartile: PA < 3.7°, 2) second quartile: PA 3.7–4.1°, 3) third quartile: PA 4.2–4.9°and 4) forth quartile: PA ≥ 5.0°. International Society of Renal Nutrition and Metabolism (ISRNM) criteria and Japanese version of Cardiovascular Health Study (J-CHS) criteria were used to identify PEW and frailty.ResultsThe lower PA group was associated with a greater risk of PEW (35% vs. 24% vs. 21% vs. 3%; p = 0.032), frailty (59% vs. 40% vs. 21% vs. 3%; p < 0.001). In multivariate logistic regression analysis, the first quartile group was at a significantly greater risk of both PEW and frailty compared with the fourth quartile group after adjusting for other confounding factors.ConclusionsLower PA was associated with a greater risk of PEW and frailty in HD patients.

Markers of protein-energy wasting and physical performance in haemodialysis patients: A cross-sectional study

Physical impairments are common in uraemia, as reflected by the high risk of falls of haemodialysis (HD) patients. Furthermore, these patients often suffer from malnutrition. Up to now, it is unknown which aspects of physical performance are predominantly driven by malnutrition in HD patients. As this answer could steer different interventions, the aim of this study was to evaluate the cross-sectional relationship between nutritional status, muscle strength, exercise capacity and the risk of falls. This study recruited HD patients between December 2016 and March 2018 from two hospital-based and five satellite dialysis units (registration number on clinicaltrial.gov: NCT03910426). The mini-nutritional assessment scale as well as objective measures of protein-energy wasting were obtained (total iron-binding capacity, total protein levels, and CRP). Physical assessment included muscle strength (quadriceps, handgrip force, and sit-to-stand test), exercise capacity (six-minute walking test) and the risk of falls (Tinetti, FICSIT, and dialysis fall index). Their interrelationship was analysed by ridge regression models. Out of 113 HD patients (mean age 67 years ± 16.1, 57.5% male) 36.3% were malnourished according to the mini-nutritional assessment scale and a majority had impaired quadriceps force (86.7%), six-minute walking test (92%), and an increased risk of falls (73.5%). Total protein and CRP levels were identified as relevant nutritional factors in the association with physical performance. Nutritional parameters explained 9.2% of the variance in the risk of falls and 7.6% of the variance in exercise capacity. No conclusive association was found between nutritional status and muscle strength. Protein-energy wasting is a determinant of the risk of falls and exercise capacity in patients on HD. The association between malnutrition and muscle weakness remains inconclusive.

Predictors of protein-energy wasting in haemodialysis patients: a cross-sectional study.

Protein-energy wasting (PEW) is a highly prevalent condition in haemodialysis patients (HD). The potential usefulness of nutritional-inflammatory markers in the diagnosis of PEW in chronic kidney disease has not been established completely. We hypothesised that a combination of serum albumin, percentage of mid-arm muscle circumference and standard body weight comprises a better discriminator than either single marker of nutritional status in HD patients. A cross-sectional study was performed in 80 HD patients. Patients were categorised in two groups: well-nourished and PEW. Logistic regression analysis was applied to corroborate the reliability of the three markers of PEW with all the nutritional-inflammatory markers analysed. PEW was identified in 52.5% of HD patients. Compared with the well-nourished patients, PEW patients had lower body mass index, serum pre-albumin and body cell mass (all P<0.001) and higher C-reactive protein (s-CRP) (P<0.01). Logistic regression analyses showed that the combination of the three criteria were significantly related with s-CRP >1mg dL(-1) , phase angle <4°, and serum pre-albumin <30mg dL(-1) (all P<0.05). Other indicators, such as lymphocytes <20% and Charlson comorbidity index, were significantly involved (both P<0.01). A receiver operating characteristic curve (area under the curve) of 0.86 (P<0.001) was found. The combined utilisation of serum albumin, percentage of mid-arm muscle circumference and standard body weight as PEW markers appears to be useful for nutritional-inflammatory status assessment and adds predictive value to the traditional indicators. Larger studies are needed to achieve the reliability of these predictor combinations and their cut-off values in HD patients and other populations.

Apolipoprotein A‐IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus – a post hoc analysis of the 4D Study

Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apoA-IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. This post hoc analysis was performed in the German Diabetes Dialysis Study (4D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apoA-IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index (BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. Mean (±SD) apoA-IV concentration was 49.8 ± 14.2 mg dL(-1). Age- and gender-adjusted apoA-IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL(-1) increase; P < 0.001). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio (HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m(-2) (HR = 0.87, 95% CI 0.82-0.94, P < 0.001) and those in the nonwasting group according to the extended definition (HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apoA-IV at baseline. Further associations were observed for sudden cardiac death. ApoA-IV was less strongly associated with atherogenic events such as myocardial infarction. Low apoA-IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status.

Association of Relatively Low Serum Parathyroid Hormone With Malnutrition-Inflammation Complex and Survival in Maintenance Hemodialysis Patients

Low serum parathyroid hormone (PTH) has been implicated as a primary biochemical marker of adynamic bone disease in individuals with chronic kidney disease (CKD) who undergo maintenance hemodialysis (MHD) treatment. We hypothesized that the malnutrition-inflammation complex is associated with low PTH levels in these patients and confounds the PTH-survival association. We examined 748 stable MHD outpatients in southern California and followed them for up to 5 years (October 2001-December 2006). In 748 MHD patients, serum PTH <150pg/mL was more prevalent among non-blacks and diabetics. There was no association between serum PTH and coronary artery calcification score, bone mineral density, or dietary protein or calorie intake. Low serum PTH was associated with markers of protein-energy wasting and inflammation, and this association confounded the relationship between serum PTH and alkaline phosphatase. Although 5-year crude mortality rates were similar across PTH increments, after adjustment for the case-mix and surrogates of malnutrition and inflammation, a moderately low serum PTH in 100-150pg/mL range was associated with the greatest survival compared to other serum PTH levels, i.e., a death hazard ratio of 0.52 (95% confidence interval: 0.29-0.92, p<0.001) compared to PTH of 300-600pg/mL (reference). Low serum PTH may be another facet of the malnutrition-inflammation complex in CKD, and after controlling for this confounder, a moderately low PTH in 100-150pg/mL range appears associated with the greatest survival. Limitations of observational studies should be considered.

Outcome predictability of biomarkers of protein-energy wasting and inflammation in moderate and advanced chronic kidney disease

Background:Markers of protein-energy wasting (PEW) and inflammation are common in chronic kidney disease (CKD) and are among the strongest predictors of mortality in dialysis patients. Objective:We hypothesized that markers of PEW and inflammation show similar associations in patients with non-dialysis-dependent CKD (NDD-CKD). Design:We examined the associations of serum albumin, white blood cell (WBC) count, percentage of lymphocytes in WBCs (%LYM), and a combination of all 3 with all-cause mortality and with the composite of predialysis mortality or end-stage renal disease (ESRD) by using fixed-covariate and time-dependent Cox models in 1220 men with NDD-CKD. Results:Lower albumin and %LYM and a higher WBC count were significantly associated with outcomes. In time-dependent Cox models, compared with patients in whom none of these markers indicated PEW, those in whom 1, 2, or all 3 markers indicated the presence of PEW had multivariable-adjusted hazard ratios (95% CI) for all-cause mortality of 1.7 (1.2, 2.4), 2.4 (1.7, 3.4), and 3.6 (2.5, 5.1); theP for trend was <0.001. Similar associations were present in fixed-covariate models for all-cause mortality and in fixed-covariate and time-dependent models for the composite outcome. Conclusions:Traditional and nontraditional markers of PEW display robust, strong, and independent associations with mortality in patients with NDD-CKD. Clinical trials are warranted to examine whether PEW-improving interventions can lead to better outcomes in these patients.

Review article: Biomarkers of clinical outcomes in advanced chronic kidney disease.

Chronic kidney disease (CKD) is a complex condition, where the decrease in kidney function is accompanied by numerous metabolic changes affecting virtually all the organ systems of the human body. Many of the biomarkers characteristic of the individually affected organ systems have been associated with adverse outcomes including higher mortality in advanced CKD, whereas in persons without CKD these biomarkers may have no bearing on survival. It is believed that the high mortality seen in CKD is a result of several abnormalities conspiring to induce or aggravate a heightened degree of cardiovascular morbidity and predisposition to wasting syndrome. Not all the biomarkers may, however, be causally responsible for the adverse outcomes associated with them. We review various biomarkers of protein-energy wasting, inflammation, oxidative stress, potassium disarrays, acid-base disorders, bone and mineral disorders, glycemic status, and anemia. Although all of these biomarkers have shown associations with worsened outcomes in CKD, markers of protein-energy wasting, especially serum albumin, remain the strongest predictor of survival in CKD patients, especially those undergoing maintenance dialysis treatment. We also review the putative pathophysiologic mechanisms behind these associations, and present potential therapeutic interventions that could result in remedies to improve poor clinical outcomes in CKD, pending the results of current and future controlled trials.

Association of Serum Total Iron-Binding Capacity and Its Changes Over Time with Nutritional and Clinical Outcomes in Hemodialysis Patients

Serum transferrin, estimated by total iron-binding capacity (TIBC), may be a marker of protein-energy wasting (PEW) in maintenance hemodialysis (MHD) patients. We hypothesized that low TIBC or its fall over time is associated with poor clinical outcomes. In 807 MHD patients in a prospective 5-year cohort, associations of TIBC and its changes over time with outcomes were examined after adjustment for case-mix and markers of iron stores and malnutrition-inflammation including serum interleukin-6, iron and ferritin. Patients with serum TIBC ≥250 mg/dl had higher body mass index, triceps and biceps skinfolds and mid-arm muscle circumference and higher serum levels of iron but lower ferritin and inflammatory markers. Some SF-36 quality of life (QoL) components were worse in the lowest and/or highest TIBC groups. Mortality was incrementally higher in lower TIBC levels (p-trend <0.001). Adjusted death hazard ratio was 1.75 (95% CI: 1.00–3.05, p = 0.05) for TIBC <150 compared to TIBC of 200–250 mg/dl. A fall in TIBC >20 mg/dl over 6 months was associated with a death hazard ratio of 1.57 (95% CI: 1.04–2.36, p = 0.03) compared to the stable TIBC group. Hence, low baseline serum TIBC is associated with iron deficiency, PEW, inflammation, poor QoL and mortality, and its decline over time is independently associated with increased death risk.

Why Is Protein–Energy Wasting Associated With Mortality in Chronic Kidney Disease?

Observational studies in chronic kidney disease (CKD) populations consistently have shown the strong mortality-predictability of such markers of protein-energy wasting (PEW) as hypoalbuminemia, low serum cholesterol levels, low body mass index, and reduced dietary protein intake. Even though the PEW-mortality association data traditionally are reported mostly in maintenance dialysis patients, emerging studies extend the existence of these associations to predialysis stages of CKD. Paradoxic risk factor patterns (reverse epidemiology) for both obesity and cholesterol recently have been reported in predialysis CKD, underscoring the overwhelming impact of PEW, a short-term killer, on reversing the long-term effect of conventional cardiovascular risk factors. Multiple pathophysiologic mechanisms have been suggested to explain the link between PEW and mortality in CKD, including derangements in muscle, adipose tissue, and the gastrointestinal, hematopoietic, and immune systems; complications related to deficiencies of multiple micronutrients; and the maladaptive activation of the inflammatory cascade. In addition to well-described pathophysiologic mechanisms involved in the higher mortality seen with PEW, we also discuss the potential role of novel factors such as circulating actin, gelsolin, and proinflammatory high-density lipoprotein. Whether PEW is causally related to adverse outcomes in CKD needs to be verified in randomized controlled trials of nutritional interventions. The initiation of major clinical trials targeting nutritional interventions with the goal of improving survival in CKD offer the promise of extending the survival of this vulnerable patient population.