Relative contributions of nutrition and inflammation to clinical outcome in dialysis patients

doi:10.1053/ajkd.2001.29250

American Journal of Kidney Diseases

Volume 38, Issue 6, December 2001, Pages 1343-1350

https://doi.org/10.1053/ajkd.2001.29250 Get rights and content

Abstract

Protein-energy malnutrition (PEM) is a common phenomenon in maintenance dialysis (MD) patients and a risk factor for poor quality of life and increased morbidity and mortality, including cardiovascular death, in these individuals. The association between undernutrition and adverse outcome in MD patients, which stands in contrast to that seen in the general population, has been referred to as reverse epidemiology. Measures of food intake, body composition tools, nutritional scoring systems, and laboratory values are used to assess the degree of severity of PEM, but no uniform approach is available for rating the overall severity of PEM. Epidemiologic studies suggest that inflammation is a missing link between PEM and poor clinical outcome in MD patients, and the existence of a malnutrition inflammation complex syndrome is suggested in these patients. Inflammation may be due to subclinical and clinically apparent illnesses. Some investigators suggest that PEM may predispose to illness and inflammation. There is a paucity of information concerning the effect of nutritional therapy on morbidity and mortality in MD patients. Interventional studies of the effect of nutritional support on outcome often are difficult to interpret because of small sample sizes, short duration of study, and other limitations. Large-scale, randomized, clinical trials of the effects of nutritional intake, nutritional status, and inflammation on clinical outcome are needed to define better the relationships between these factors in MD patients. © 2001 by the National Kidney Foundation, Inc.

Section snippets

Protein-energy malnutrition

Many studies have found significant correlations between measures of PEM and such clinical outcomes as increased rate of hospitalization, mortality, and worsened quality of life in MD patients.2, 4, 5 Indicators of PEM in MD patients include decreased dietary protein and energy intake; reduced serum albumin, prealbumin, transferrin, cholesterol, creatinine, and insulin-like growth factor-1 concentrations; decreased total body nitrogen and total body potassium; decreased weight-for-height and

Nutrient intake

A low normalized protein equivalent of total nitrogen appearance (nPNA), also known as normalized protein catabolic rate, is believed to reflect the daily protein intake and is among the monthly reported laboratory measures in many dialysis centers.¹⁶ The nPNA, which may be confounded because of its mathematical coupling with Kt/V, has been shown in some but not all studies to be a predictor of hospitalization and mortality in MD patients.4, 17 We have shown that among MD patients who have a

Inflammation and oxidative stress

Epidemiologic evidence suggests that inflammation, including but not limited to some specific low-grade infections, such as Chlamydia pneumoniae, is a risk factor for cardiovascular diseases and mortality in the general population.21, 22 The mechanisms by which inflammation promotes cardiovascular disease are the subject of intense investigation in nonuremic populations. Data indicate that inflammatory processes promote proliferation and infiltration of inflammatory cells into the tunica intima

Interaction between protein-energy malnutrition and inflammation

The pathophysiology by which PEM is associated with increased mortality, particularly from cardiovascular disease, has not been well defined in MD patients.4, 5, 33 The association of PEM with inflammation in these patients may explain this dilemma.10, 11, 12, 13 Several investigators suggest that PEM is a consequence of chronic inflammatory processes in ESRD patients.10, 33 According to this model, inflammation is associated with a rise in plasma and probably tissue levels of catabolic

Is protein-energy malnutrition an independent cause of adverse outcome?

The extent to which PEM and inflammation may be causes of each other and the degree to which they can cause adverse outcomes independently in MD patients has not been defined clearly. The data that so far connect PEM to inflammation are epidemiologic in nature, and there is a paucity of interventional studies that could evaluate more definitively the interrelationships between PEM, inflammation, and outcome in MD patients. It also is unclear as to the degree to which PEM is an independent cause

Nutritional support and dialysis outcome

Experience with nutritional support of sick or malnourished individuals may provide some insight as to the independent role of PEM on clinical outcome in MD patients. Ample evidence suggests that maintaining an adequate nutritional intake in patients with many acute or chronic catabolic illnesses may improve their nutritional status⁶⁰ and, in some studies, reduce morbidity and mortality and improve quality of life.⁵⁰ The evidence as to whether nutritional treatment may improve morbidity and

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The Relationship Between Myostatin, Inflammatory Markers, and Sarcopenia in Patients With Chronic Kidney Disease
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To determine the prevalence of sarcopenia in patients with chronic kidney disease (CKD), investigate the relationship of the serum myostatin level with sarcopenia and inflammatory markers.
The study was conducted with four patient groups: renal transplantation (TX), stage 3-5 non–dialysis-dependent CKD (NDD-CKD), hemodialysis (HD), and peritoneal dialysis (PD). Laboratory parameters, serum myostatin, C-reactive protein, and interleukin-6 levels were studied. Body composition was estimated using a multifrequency bioimpedance analysis. Handgrip strength (HGS) was evaluated with a handgrip dynamometer. The HGS and appendicular skeletal muscle index measurements were used to determine sarcopenia presence.
The study included 130 patients (72 [55%] male patients). The patient distribution in groups was as follows: 37 in HD, 28 in PD, 37 in renal TX, and 28 in NDD-CKD. The highest level of myostatin was measured in the HD group, and the lowest in the TX group (P < .001). The HGS measurement in the PD group was significantly lower than that in the TX group (P = .025). The myostatin was negatively correlated with HGS, albumin, estimated glomerular filtration rate, and Kt/V_urea. However, myostatin had no correlation with inflammatory markers or appendicular skeletal muscle index. Sarcopenia was present in 37 (29%) patients: 15 (40%) in the HD group, nine (32%) in NDD-CKD, seven (25%) in PD, and six (16%) in TX. When the patients with and without sarcopenia were compared, only myostatin was higher in the former (P = .045). As a result of multivariate analysis, myostatin was the only independent factor which predicts sarcopenia (odds ratio: 1.002, 95% confidence interval: 1.001-1.005, P = .048).
To prevent devastating events associated with sarcopenia in patients with CKD, renal transplantation seems to be the best treatment solution. For the early recognition of sarcopenia, the measurement of the serum myostatin level may be a promising diagnostic approach.
Predictive Value of Objective Nutritional Indexes in Technique Failure in Peritoneal Dialysis Patients
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Patients undergoing peritoneal dialysis (PD) will encounter with a well-recognized challenge of technique failure (TF). We aimed to explore the predictive value of objective nutritional indexes in PD TF.
This retrospective observational study included PD patients from August 2010 to March 2019. The Controlling Nutritional Status (CONUT) score, Prognostic Nutritional Index (PNI), and Geriatric Nutritional Risk Index (GNRI) were calculated at baseline. TF was defined as a permanent switch from PD to hemodialysis. Univariate and multivariate Cox regression was performed to investigate the association between confounding factors and outcomes. The optimal cut-off values were determined using receiver operating characteristic curve analysis. We used the Kaplan-Meier curve to compare the outcomes according to the cut-off values. The area under the curve (AUC) was used to test discriminative power of these objective nutritional indexes.
We analyzed 276 PD patients, 84 (30.43%) experienced TF during 2.5 (1.4, 4.0) years of follow-up. In the Kaplan-Meier analysis, patients with a higher CONUT score (>3), lower GNRI (≤85.77), and lower PNI (≤40.2) had significantly higher risk of TF (38.2% vs. 18.9%, P = .011; 39.6% vs. 25.1%, P = .043; 35.9% vs. 17.9%, P = .022; respectively). After adjusting confounding factors, a high CONUT score and low PNI were independently and significantly associated with TF analyzed by a multivariate Cox regression model (hazard ratio 2.284, 95% confidence interval [CI] 1.248-4.179, P = .007; hazard ratio 2.070, 95% CI 1.233-3.475, P = .006; respectively). The largest AUC to predict TF was PNI (AUC 0.600, 95% CI 0.539-0.658), followed by CONUT score (AUC 0.596, 95% CI 0.535-0.654) and GNRI (AUC 0.572, 95% CI 0.511-0.631).
The CONUT score and PNI are independently associated with TF in PD patients. Moreover, assessment of PNI and the CONUT score may provide more useful predictive values than GNRI.
Technique failure; peritoneal dialysis; geriatric nutritional risk index; controlling nutritional status; prognostic nutritional index
Systemic inflammation May limit the effect of protein supplement on nutritional status in peritoneal dialysis
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Citation Excerpt :
In the present study, as both groups of patients tended to increase their nutrient intake, it is less probable that such anorexigenic effects has been present. Alternatively, a greater proteolysis or a lower protein synthesis induced by inflammation in CAPD patients [26] could be implicated. Patients with inflammation had a trend to show higher BMI and TSF [reflecting fat depots associated with intense pro-inflammatory activity [27]], whereas a higher (although non-statistically significant) increase of MAMA [which reflects muscle protein reserve [28]] and serum albumin [visceral protein reserve [12]] was observed in those subjects without inflammation.
Malnutrition and inflammation are highly prevalent and associated with poor outcomes in continuous ambulatory peritoneal dialysis (CAPD). Nutritional supplements are commonly used; however, presence of systemic inflammation could limit their effect.
To evaluate the impact of systemic inflammation on nutritional status of CAPD patients receiving an oral protein supplement.
Prospective observational study; 34 malnourished patients (subjective global assessment; SGA) received both nutritional counseling and oral egg albumin-based protein supplement. During 6-month of follow-up, patients had monthly clinical, and quarterly biochemical and inflammation [interleukin 6 and high sensitivity C-reactive protein (hsCRP)] evaluations. According to baseline hsCRP, patients were classified in two groups: Inflammation (>3 mg/L) and No-inflammation (≤3 mg/L).
Comparing baseline vs final, macronutrient intake and SGA increased in both groups, however, improvement of SGA was more marked in the No-inflammation group at the end of the study: 70% improved, 25% no change and 5% worsened (p = 0.001); whereas in the Inflammation group results were: 50% improved, 36% no change and 14% worsened (p = 0.03). Additionally, at final evaluation, serum albumin tended to increase more in the No-inflammation (3.0 ± 0.9 vs 3.4 ± 1.1 g/dL, p = 0.08) than in Inflammation group (2.8 ± 0.6 vs 3.0 ± 0.9 g/dL, p = 0.66), and body mass index significantly increased in No-inflammation group (20.3 ± 3.0 vs 21.6 ± 3.3 kg/m², p < 0.001) but not in Inflammation group (21.9 ± 3.0 vs 22.5 ± 3.3 kg/m², p = 0.09).
The presence of systemic inflammation in malnourished CAPD patients seemed to limit the trend for improvement on nutritional status observed with counseling and oral egg albumin-based protein supplement in patients without inflammation.
Dietary protein intake and the risk of all-cause and cardiovascular mortality in maintenance hemodialysis patients: A multicenter, prospective cohort study
2022, Nutrition
The association between dietary protein intake (DPI) and mortality in people receiving maintenance hemodialysis (MHD) remains uncertain. We aimed to explore the relationship of DPI with all-cause and cardiovascular (CV) mortality, and to examine the possible modifiers for the associations, in Chinese MHD patients.
This multicenter prospective cohort study was conducted in eight outpatient dialysis centers in South China. We enrolled 1044 MHD patients in 2014 and 2015. The DPI was assessed using a 3-d 24-h dietary recall. Using Cox proportional hazard models, we estimated the hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) for all analyzed end points.
During a median follow-up of 45 mo, there were 354 (33.9%) deaths, 210 of which were CV related. Compared with patients with a DPI of 1.0 to < 1.4 g/kg ideal body weight (IBW)/d, a significantly higher risk of all-cause mortality was found in those with a DPI < 1.0 g/kg IBW/d (adjusted HR, 1.84; 95% CI, 1.42–2.38) or ≥ 1.4 g/kg IBW/d (adjusted HR, 1.49; 95% CI, 1.00–2.22). Similar trends were found for CV mortality. Moreover, we found a significantly stronger positive association between DPI (≥ 1.4 versus 1.0 to < 1.4 g/kg IBW/d) and all-cause mortality in women (adjusted HR, 2.05; 95% CI, 1.00–4.22) than in men (adjusted HR, 0.89; 95% CI, 0.49–1.63; P for interaction = 0.0487).
In Chinese MHD patients, a DPI of 1.0 to < 1.4 g/kg IBW/d was associated with lower risks of all-cause and CV mortality.
Association between Body Mass Index and Chronic Kidney Disease in Asian Populations: A Participant-level Meta-Analysis
2021, Maturitas
Obesity and chronic kidney disease (CKD) are major public health problems worldwide. However, the association between body mass index (BMI) and CKD is inconclusive in Asians. In this meta-analysis, eight population-based studies, from China, India, Russia (Asian), Singapore and South Korea, provided individual-level data (n=50037). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². BMI was analyzed both as a continuous variable and in three categories: <25kg/m², normal; 25–29.9kg/m², overweight; and ≥30kg/m², obese. The association between BMI and CKD was evaluated in each study using multivariable logistic regression models and individual estimates were pooled using random-effect meta-analysis to obtain the pooled odds ratio (OR) and 95% confidence interval (CI). Associations were also evaluated in subgroups of age, gender, smoking, diabetes, and hypertension status. Of 50037 adults, 4258 (8.5%) had CKD. 13328 (26.6%) individuals were overweight while 4440 (8.9%) were obese. The prevalence of any CKD ranged from 3.5% to 29.1% across studies. In pooled analysis, both overweight and obesity were associated with increased odds of CKD, with pooled OR (95% CI) of 1.15 (1.03-1.29) and 1.23 (1.06-1.42), respectively. In subgroup analyses, significant associations between BMI and CKD were observed in adult males, non-smokers, and those with diabetes and arterial hypertension (all p<0.05). When evaluated as a continuous variable, BMI was not significantly associated with CKD. If confirmed in longitudinal studies, these results may have clinical implications in risk stratification and preventive measures, given that obesity and CKD are two major chronic diseases with substantial public health burden worldwide.
Association between geriatric nutritional risk index and stroke risk in hemodialysis patients: 10-Years outcome of the Q-Cohort study
2021, Atherosclerosis
The geriatric nutritional risk index (GNRI), which is calculated using the serum albumin level and body mass index, is a nutritional marker associated with an increased risk of cardiovascular events in patients who are receiving hemodialysis. However, no studies have examined the association between the GNRI level and the incidence of stroke in this population.
Three thousand forty-five patients were registered in the Q-Cohort Study, which is a multicenter, observational cohort of hemodialysis patients. The main outcomes were brain infarction and brain hemorrhage. The main exposure was GNRI levels at baseline. Patients were divided into quartiles on the basis of baseline GNRI levels: Q1, <90.7; Q2, 90.7–95.5; Q3, 95.6–99.8; Q4, >99.8. The risk of brain infarction or hemorrhage was estimated using the multivariable-adjusted Cox proportional hazard risk models and restricted cubic spline analyses.
During the 10-year follow-up period, 326 patients developed brain infarction and 149 patients developed brain hemorrhage. Cox proportional hazard risk models showed that the risk of brain infarction and hemorrhage in Q1 was significantly higher than that in Q4 group. The hazard ratios [95% confidence intervals] were 1.49 [1.05–2.12] and 1.89 [1.11–3.20], respectively. Restricted cubic spline curves showed that a lower GNRI was incrementally associated with an increased risk for both brain infarction and brain hemorrhage.
Our results suggest that a lower GNRI is an independent risk factor for both brain infarction and hemorrhage in patients who are receiving maintenance hemodialysis.

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: Address reprint requests to Joel D. Kopple, MD, Department of Medicine and Public Health, Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Harbor Mailbox 406, 100 West Carson Street, Torrance, CA 90509-2910. E-mail: [email protected]

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Symposium Proceedings: Improving Prognosis for Kidney Disorders in the 21st Century: Hypertension, Anemia, Nutrition, and LipidsRelative contributions of nutrition and inflammation to clinical outcome in dialysis patients

Abstract

Section snippets

Protein-energy malnutrition

Nutrient intake

Inflammation and oxidative stress

Interaction between protein-energy malnutrition and inflammation

Is protein-energy malnutrition an independent cause of adverse outcome?

Nutritional support and dialysis outcome

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney

Am J Kidney Dis

Am J Kidney Dis

Am J Clin Nutr

Kidney Int

Am J Kidney Dis

Am J Clin Nutr

Am J Kidney Dis

Kidney Int

Kidney Int

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

J Ren Nutr

J Ren Nutr

Kidney Int

J Ren Nutr

J Ren Nutr

Am J Clin Nutr

Am J Kidney Dis

Am J Kidney Dis

USRD 2000 Annual Data Report: Atlas of End Stage Renal Diseases in the United States

Why do we need outcomes research in end stage renal disease?

J Nephrol

Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients

ASAIO J

Symposium Proceedings: Improving Prognosis for Kidney Disorders in the 21st Century: Hypertension, Anemia, Nutrition, and Lipids
Relative contributions of nutrition and inflammation to clinical outcome in dialysis patients