Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition and Metabolism (ISRNM)

doi:10.1053/J.JRN.2013.01.001

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Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition and Metabolism (ISRNM)

Journal Article•DOI•

Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition and Metabolism (ISRNM)

Juan Jesus Carrero¹, Peter Stenvinkel¹, Lilian Cuppari², T. Alp Ikizler³, Kamyar Kalantar-Zadeh⁴, George A. Kaysen⁵, William E. Mitch⁶, S. Russ Price⁷, S. Russ Price⁸, Christoph Wanner⁹, Angela Yee-Moon Wang¹⁰, Pieter ter Wee¹¹, Harold A. Franch⁷, Harold A. Franch⁸ - Show less +10 more•Institutions (11)

Karolinska Institutet¹, Federal University of São Paulo², Vanderbilt University³, University of California, Irvine⁴, University of California, Davis⁵, Baylor College of Medicine⁶, Emory University⁷, United States Department of Veterans Affairs⁸, University of Würzburg⁹, University of Hong Kong¹⁰, VU University Amsterdam¹¹

01 Mar 2013-Journal of Renal Nutrition (W.B. Saunders Ltd)-Vol. 23, Iss: 2, pp 77-90

TL;DR: This consensus statement of current knowledge on the etiology of PEW syndrome in CKD is provided to increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of Pew.

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About: This article is published in Journal of Renal Nutrition.The article was published on 2013-03-01 and is currently open access. It has received 628 citations till now. The article focuses on the topics: Wasting & Kidney disease.

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Journal Article•DOI•

KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update

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T. Alp Ikizler, Jerrilynn D. Burrowes, Laura Byham-Gray, Katrina L. Campbell, Juan Jesus Carrero, Winnie Chan, Denis Fouque, Allon N. Friedman, Sana Ghaddar, D. Jordi Goldstein-Fuchs, George A. Kaysen, Joel D. Kopple, Daniel Teta, Angela Yee-Moon Wang, Lilian Cuppari - Show less +11 more

01 Sep 2020-American Journal of Kidney Diseases

TL;DR: The 2020 update to the KDOQI Clinical Practice Guideline for Nutrition in CKD provides comprehensive up-to-date information on the understanding and care of patients with chronic kidney disease (CKD), especially in terms of their metabolic and nutritional milieu for the practicing clinician and allied health care workers.

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670 citations

Journal Article•DOI•

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism

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T. Alp Ikizler¹, Noël Cano, Harold A. Franch², Denis Fouque, Jonathan Himmelfarb³, Kamyar Kalantar-Zadeh⁴, Martin K. Kuhlmann, Peter Stenvinkel⁵, Pieter Terwee⁶, Daniel Teta⁷, Angela Yee-Moon Wang⁸, Christoph Wanner⁹ - Show less +8 more•Institutions (9)

Vanderbilt University¹, Emory University², University of Washington³, University of California, Irvine⁴, Karolinska Institutet⁵, VU University Amsterdam⁶, University Hospital of Lausanne⁷, University of Hong Kong⁸, University of Würzburg⁹

01 Dec 2013-Kidney International

TL;DR: In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores.

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493 citations

Journal Article•DOI•

Mechanisms of muscle wasting in chronic kidney disease

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Xiaonan H. Wang¹, William E. Mitch²•Institutions (2)

Emory University¹, Baylor College of Medicine²

01 Sep 2014-Nature Reviews Nephrology

TL;DR: Myostatin inhibition could yield new therapeutic directions for blocking muscle protein wasting in CKD or disorders associated with its complications, suggesting that therapeutic strategies will be developed to suppress or block protein loss.

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Abstract: Muscle atrophy frequently complicates the course of chronic kidney disease (CKD) and is associated with excess morbidity and mortality. In this Review, the authors describe how CKD stimulates catabolic pathways that interfere with cellular protein metabolism and discuss how knowledge of these pathways might enable the development of therapies to block muscle wasting in catabolic conditions.

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428 citations

Journal Article•DOI•

Comparative Associations of Muscle Mass and Muscle Strength with Mortality in Dialysis Patients

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Naohito Isoyama¹, Abdul Rashid Qureshi², Carla Maria Avesani³, Bengt Lindholm², Peter Bárány², Olof Heimbürger², Tommy Cederholm⁴, Peter Stenvinkel², Juan Jesus Carrero⁵, Juan Jesus Carrero² - Show less +6 more•Institutions (5)

Yamaguchi University¹, Baxter International², Rio de Janeiro State University³, Uppsala University⁴, Karolinska Institutet⁵

07 Oct 2014-Clinical Journal of The American Society of Nephrology

TL;DR: Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass.

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Abstract: Background and objectives Reduced muscle mass and strength are prevalent conditions in dialysis patients. However, muscle strength and muscle mass are not congruent; muscle strength can diminish even though muscle mass is maintained or increased. This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination ( i.e., concurrent loss of muscle mass and strength/mobility, here defined as sarcopenia). Design, setting, participants, & measurements This study included 330 incident dialysis patients (203 men, mean age 53±13 years, and mean GFR 7±2 ml/min per 1.73 m 2 ) recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low muscle strength (by handgrip) were defined against young reference populations according to the European Working Group on Sarcopenia in Older People. Results Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength alone were observed in a further 24% and 15% of patients, respectively. Old age, comorbidities, protein-energy wasting, physical inactivity, low albumin, and inflammation associated with low muscle strength, but not with low muscle mass (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and both conditions associated with mortality as separate entities. When combined, individuals with low muscle mass alone were not at increased risk of mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 0.56 to 2.67). Individuals with low muscle strength were at increased risk, irrespective of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low (HR, 1.93; 95% CI, 1.01 to 3.71). Conclusions Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass. Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation.

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373 citations

Cites background from "Etiology of the Protein-Energy Wast..."

...Markers of both muscle mass and strength are important predictors of outcomes in this patient population (2,3) subjected to a catabolic protein-energy wasting (PEW) syndrome (4)....
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Journal Article•DOI•

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism

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Juan Jesus Carrero¹, Fridtjof Thomas², Kristof Nagy³, Fatiu A Arogundade⁴, Carla Maria Avesani¹, Carla Maria Avesani⁵, Maria F. Chan⁶, Michał Chmielewski⁷, Antonio C. Cordeiro, Ángeles Espinosa-Cuevas, Enrico Fiaccadori⁸, Fitsum Guebre-Egziabher⁹, Rosa K. Hand¹⁰, Adriana M. Hung¹¹, Adriana M. Hung¹², Talat Alp Ikizler¹², Talat Alp Ikizler¹¹, Lina Johansson¹³, Kamyar Kalantar-Zadeh¹⁴, Tilakavati Karupaiah¹⁵, Bengt Lindholm¹, Peter Marckmann, Denise Mafra¹⁶, Rulan S. Parekh¹⁷, Jongha Park¹⁸, Sharon Russo¹⁷, Anita Saxena¹⁹, Siren Sezer²⁰, Daniel Teta²¹, Pieter M. ter Wee²², Cecile Verseput, Angela Yee-Moon Wang²³, Hong Xu¹, Yimin Lu²¹, Miklos Z. Molnar², Csaba P. Kovesdy² - Show less +32 more•Institutions (23)

Karolinska Institutet¹, University of Tennessee Health Science Center², Semmelweis University³, Obafemi Awolowo University⁴, Rio de Janeiro State University⁵, St George's Hospital⁶, Gdańsk Medical University⁷, University of Parma⁸, Claude Bernard University Lyon 1⁹, University of Ulsan¹⁰, Vanderbilt University¹¹, Veterans Health Administration¹², Imperial College Healthcare¹³, University of California, Irvine¹⁴, Taylors University¹⁵, Federal Fluminense University¹⁶, University of Toronto¹⁷, Case Western Reserve University¹⁸, Sanjay Gandhi Post Graduate Institute of Medical Sciences¹⁹, Başkent University²⁰, University of Lausanne²¹, VU University Amsterdam²², University of Hong Kong²³

01 Nov 2018-Journal of Renal Nutrition

TL;DR: It is concluded that PEW is a common phenomenon across the spectrum of AKI and CKD, and the well-documented impact of PEW on patient outcomes justifies the need for increased medical attention.

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202 citations

Cites background or methods from "Etiology of the Protein-Energy Wast..."

...The search string consisted of two parts: (1) the exposure (i....
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...The following information was abstracted from each study and entered into the MetaXL data set: (1) first author’s name, (2) PubMed-Indexed for MEDLINE number, (3) year of publication, (4) country, (5) geographical region, (6) type of population (pediatric, AKI, Tx, CKD, or dialysis), (7) total number of patients, (8) number of patients with PEW, and (9) method of PEW definition (SGA or MIS)....
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...For brevity in our tables and figures, we make the following exceptions from theM49 Standard names: (1) ‘‘Hong Kong’’ refers to China, Hong Kong Special Administrative Region; (2) ‘‘Korea’’ to the Republic of Korea; (3) ‘‘Taiwan’’ to the island of Taiwan; (4) ‘‘UK’’ to the United Kingdom of Great Britain and Northern Ireland; (5) ‘‘USA’’ to the United States of America; (6) ‘‘Iran’’ to Iran (Islamic Republic of)....
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...Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx)....
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...Study Population, Inclusion/Exclusion Criteria The study population included the following groups of patients within the spectrum of kidney diseases that were analyzed separately: (1) acute kidney injury (AKI), (2) pediatric CKD patients, (3) adult nondialysis-dependent patients with CKD stages 3-5, (4) adult dialysis-dependent patients, and (5) in patients undergoing kidney transplantation (Tx)....
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References

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O'Brien's

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Buttolph, Frank E., Miss (d. ), Collector

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16,220 citations

Journal Article•DOI•

Cachexia: a new definition.

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William J. Evans¹, John E. Morley¹, Josep M. Argilés¹, Connie W. Bales¹, Vickie E. Baracos¹, Denis Guttridge¹, Aminah Jatoi¹, Kamyar Kalantar-Zadeh¹, H. Lochs¹, Giovanni Mantovani¹, Daniel L. Marks¹, William E. Mitch¹, Maurizio Muscaritoli¹, Armine Najand¹, Piotr Ponikowski¹, Filippo Rossi Fanelli¹, Morrie Schambelan¹, Annemie M. W. J. Schols¹, Michael W. Schuster¹, David R. Thomas¹, Robert R. Wolfe¹, Stefan D. Anker¹ - Show less +18 more•Institutions (1)

University of Arkansas for Medical Sciences¹

01 Dec 2008-Clinical Nutrition

TL;DR: The prominent clinical feature of cachexia is weight loss in adults (corrected for fluid retention) or growth failure in children (excluding endocrine disorders).

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1,948 citations

Journal Article•DOI•

A proposed nomenclature and diagnostic criteria for protein–energy wasting in acute and chronic kidney disease

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Denis Fouque¹, Kamyar Kalantar-Zadeh², Joel D. Kopple², Noël Cano, Philippe Chauveau, Lilian Cuppari³, Harold A. Franch⁴, Gabriele Guarnieri⁵, Talat Alp Ikizler⁶, George A. Kaysen⁷, Bengt Lindholm⁸, Ziad A. Massy⁹, William E. Mitch¹⁰, E. Pineda¹¹, Peter Stenvinkel⁸, A. Trevinho-Becerra¹¹, Christoph Wanner¹² - Show less +13 more•Institutions (12)

University of Lyon¹, Los Angeles Biomedical Research Institute², Federal University of São Paulo³, Emory University⁴, University of Trieste⁵, Vanderbilt University Medical Center⁶, University of California, Davis⁷, Karolinska Institutet⁸, French Institute of Health and Medical Research⁹, Baylor College of Medicine¹⁰, National Autonomous University of Mexico¹¹, University of Würzburg¹²

02 Feb 2008-Kidney International

TL;DR: An expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves.

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1,584 citations

"Etiology of the Protein-Energy Wast..." refers background in this paper

...PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD....
[...]
...Low energy and/or protein intake associates with a sig- nificant decline of nutritional parameters (including hypoalbuminemia) and increased risk of morbidity and mortality in patients with advanced CKD.3,4 In most of these studies, dietary energy and protein intakes are lower than recommended for patients undergoing either hemodialysis (HD)3,5,6 or peritoneal dialysis (PD).7,8 However, dietary recalls underestimate dietary intake,9-11 and improving accuracy of dietary monitoring is needed....
[...]
...Given the unique features of the syndrome, the International Society of Renal Nutrition and Metabolism (ISRNM) proposed a common nomenclature and diagnostic criteria for these alterations in the context of CKD.1 Protein-energy wasting (PEW) was proposed to denote concurrent losses in protein and energy stores, with cachexia being regarded as only the end stage....
[...]
...Given the unique features of the syndrome, the International Society of Renal Nutrition and Metabolism (ISRNM) proposed a common nomenclature and diagnostic criteria for these alterations in the context of CKD.(1) Protein-energy wasting (PEW) was proposed to denote concurrent losses in protein and energy stores, with cachexia being regarded as only the end stage....
[...]
...Both abnormalities correct when metabolic acidosis is treated.159 Likewise, in patients being treated by HD or PD, treatment of metabolic acidosis reduced the excessive rate of protein degradation.160,161 Longterm clinical trials show similar results in PD and CKD.162,163 Thus, acidosis contributes to PEW, and correction of acidosis ameliorates it....
[...]

Journal Article•DOI•

Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression

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Stewart H. Lecker¹, R. Thomas Jagoe, Alexander Gilbert¹, Marcelo Gomes², Vickie E. Baracos³, James L. Bailey⁴, S. Russ Price⁴, William E. Mitch⁵, Alfred L. Goldberg² - Show less +5 more•Institutions (5)

Beth Israel Deaconess Medical Center¹, Harvard University², University of Alberta³, Emory University⁴, University of Texas Medical Branch⁵

01 Jan 2004-The FASEB Journal

TL;DR: Different types of skeletal muscle atrophy share a common transcriptional program that is activated in many systemic diseases including diabetes, cancer, and renal failure, according to cDNA microarrays.

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Abstract: Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair-fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down-regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up-regulated (lipin, metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1-BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.

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1,466 citations

Journal Article•DOI•

Cytokines and major depression.

[...]

Olga J. G. Schiepers¹, Marieke Wichers¹, Michael Maes¹•Institutions (1)

Maastricht University¹

01 Feb 2005-Progress in Neuro-psychopharmacology & Biological Psychiatry

TL;DR: Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.

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Abstract: In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.

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1,131 citations