• Users Online: 193
  • Print this page
  • Email this page

Table of Contents
Year : 2019  |  Volume : 5  |  Issue : 2  |  Page : 44-47

Nutritional challenges in malnutrition, inflammation, and atherosclerosis (MIA)syndrome

1 Department of Nephrology, Renal Sciences Centre, Kanpur, Uttar Pradesh, India
2 Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission20-Dec-2019
Date of Acceptance24-Dec-2019
Date of Web Publication08-Jan-2020

Correspondence Address:
Dr. Anita Saxena
Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrnm.jrnm_56_19

Get Permissions


Headings are not required in this abstract as material and methods results etc are not involved. Patients undergoing hemodialysis (HD) have a high prevalence of protein–energy malnutrition and inflammation. As these two conditions occur concomitantly with mild-to-severe atherosclerosis in CKD, these three conditions collectively have been referred to as malnutrition-inflammation-atherosclerosis syndrome (MIA syndrome). but later studies showed that syndrome also exists in preterminal renal failure patients and PD patients. The three components not only coexist but also interact with each other. This article briefly discusses potential nutritional management of MIA syndrome.

Keywords: Atherosclerosis, inflammation, malnutrition

How to cite this article:
Kumar N, Saxena A. Nutritional challenges in malnutrition, inflammation, and atherosclerosis (MIA)syndrome. J Renal Nutr Metab 2019;5:44-7

How to cite this URL:
Kumar N, Saxena A. Nutritional challenges in malnutrition, inflammation, and atherosclerosis (MIA)syndrome. J Renal Nutr Metab [serial online] 2019 [cited 2020 Mar 28];5:44-7. Available from: http://www.jrnm.in/text.asp?2019/5/2/44/275408

  What is Malnutrition Inflammation and Atherosclerosis (MIA) Syndrome? Top

Protein–energy malnutrition with muscle wasting is common in patients with chronic kidney disease (CKD). Besides malnutrition, conditions such as inflammation and atherosclerosis are noteworthy complications, leading to increased incidence of infection, hospitalization, and cardiovascular mortality in patients with CKD. Patients undergoing hemodialysis (HD) are known to be inflicted with protein energy malnutrition and inflammation. As these two conditions occur concomitantly with mild-to-severe atherosclerosis in CKD, these three conditions collectively have been referred to as malnutrition-inflammation-atherosclerosis syndrome.[1]

How does malnutrition set in: Over time, with loss of appetite and subclinical inflammation CKD patients tend to have reduced body weight, reduced energy stores, loss of muscle mass and concomitantly loss of protein stores which reflect low levels of total protein, serum albumin, transferrin, pre-albumin and other visceral proteins. In kidney disease, the pathophysiology of malnutrition is multifactorial. Poor food intake because of anorexia, nausea and vomiting due to uraemic toxicity, gastroparesis, hormonal derangements, depression, acidosis and increased resting energy expenditure are the major factors which cause malnutrition. Of the two types of malnutrition Type and Type 2, Type 2 malnutrition is plagued with inflammation. Inflammation is the hallmark of Type 2 malnutrition, and hence this type of malnutrition is not reversible even on replenishing the nutrients. Inflammation, alone or in combination with a low protein intake, plays a significant role in causing hypoalbuminaemia [2],[3],[4],[5],[6] Above all the resting energy expenditure is also raised in Type 2 malnutrition. Wasting, infection and inflammation related cardiovascular disease are the main cause of mortality in the CKD patients. In patients who are on dialysis, the dialysis procedure per se is catabolic [7]. Factors directly associated with catabolism in dialysis procedure are bio-incompatible dialyzer membrane, nutrient (vitamins and amino acids and peptides which cause hypoalbuminemia) losses in the dialysate, and in patients on peritoneal dialysis poor appetite due to abdominal discomfort and uptake of glucose. ISRNM has proposed diagnostic criteria for PEW [8].

Inflammation in CKD is the most important factor in the genesis of several complications in renal disease which could be related to dialysis (graft and fistula infection, bio incompatibility, impure dialysate and back filtration) or un-related dialysis (acute and chronic bacterial infections, viral infections). Persistence of low grade inflammation is considered as a crucial component of MIA syndrome. It is an established fact that moderately elevated plasma concentrations of C-reactive protein (CRP) are associated with increased risk of cardiovascular disease,[6] ischemic stroke,[7] and mortality in the elderly.[9] Pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha are pivotal in the onset of metabolic alterations in CKD patients. Highly reactive oxygen species leading to persistent oxidative stress is another cause of persistent inflammation in these patients. Hyperprathyroidism, secondary to renal impairment, as a cause of imbalanced calcium phosphorus is a risk factor of coronary artery disease [Figure 1]. Atherosclerosis is accelerated in CKD by complex mechanisms involving cross talk between T-helper cell and subendothelial macrophages as antigen-presenting cells. Atherosclerosis is coexistent with hypertension, hyperhomocysteinemia, inflammation, malnutrition and increased oxidative stress, generation of advanced glycation end-products, advanced oxidation protein products, and hyperlipidemia.[10] A strong relationship has been reported between malnutrition, elevated CRP levels, and atherosclerosis in predialysis patients.[10],[11] The triggers of this response are alteration of lipid metabolism and subendothetial deposits of plasma lipoprotein.
Figure 1: Potential mechanisms by which hyperphosphatemia causes cardiovascular disease/death

Click here to view

The syndrome was initially described in patients with end-stage renal disease (ESRD) patients undergoing long-term HD, but later studies showed that syndrome also exists in preterminal renal failure patients and PD patients. The three components not only coexist but also interact with each other.[12] The presence of this syndrome was associated with very high mortality in HD patients.[13] The prevention of MIA syndrome is of utmost importance because the emergence of each of its components worsens the survival potential of ESRD patients. Majority of ESRD patients have the signs of atherosclerosis.[3],[14],[15]

Therefore, the predialysis period is the ideal time to start therapeutic interventions.[16] The real nutritional challenges and problems are interwoven with each factor of MIA syndrome separately and understand its correlation with each other.

  Challenges in the Management of Malnutrition, Inflammation, and Atherosclerosis Syndrome in Indian Scenario Top

In India, an estimated 100–220/million populations reach CKD Stage V due to the increased incidence of diabetes and hypertension.[16],[17]

Approximately only 10% of ESRD patients in India receive renal replacement therapy (RRT),[18] mainly due to socioeconomic constraints. Malnutrition in dialysis patients is common, and the prevalence varies widely between 20% and 60%. The causes of malnutrition in Indian CKD patients are late referral to nephrologist, late initiation of dialysis, at times noncompliance to dialysis schedule due to financial constraints, inadequate dialysis dose, inadequate dietary counseling due to paucity of dedicated renal dietitians, depression, and associated comorbidities. Poor appetite in these patients is usually the result of coexisting inflammation, metabolic acidosis, and hormonal derangements. Of all access-related bloodstream infections, 70% occur in patients with catheters. In Indian patients, also vascular access infections, especially blood line infections, are common, as only 15%–20% of ESRD patients initiate their dialysis with arteriovenous fistula (unpublished data). Water quality and dialyzer reuse in HD patients pose an additional inflammatory state in Indian settings. Atherosclerosis manifesting as a cardiovascular disease continues to be a significant killer in HD patients. The diagnosis of CVD is made late, and consequently, intervention is delayed. Many patients do not stick to their original prescription of statins and antiplatelets. Financial constraints limit the use of coronary angiography and percutaneous transluminal coronary angioplasty in the vast majority of Indian patients on HD.

  Management of Malnutrition in Malnutrition, Inflammation, and Atherosclerosis Syndrome Top

The main objective of medical nutrition intervention in patients with CKD is to slow progression of chronic renal failure without inducing malnutrition. Hence, before making any recommendations nutrient prescription, assessment of nutrition status should be performed [8]. Regular nutritional assessment should be conducted every 2-3 months for non-dialysed out-patients with glomerular filtration rate (GFR) <20 ml/mn is recommended. Screening for malnutrition should be more frequent when there is a malnutrition risk event.

In MIA syndrome, till inflammation is correcte, it will not be easy to reach the nutritional objectives. Alleviating anorexia, proper dietary counselling, convincing patient for oral nutritional supplements (ONS), intradialytic parenteral nutrition (IDPN) and enteral nutrition (EN) are the main challenges in the way of proper nutritional management of patients with MIA syndrome. It is not easy to reach the nutritional objectives in MIA syndrome. It requires proper dietary counseling, oral nutritional supplements, intradialytic parenteral nutrition (IDPN), and enteral nutrition. Clinical guidelines recommend the adequate calorie intake according to age and diabetic status (35 kcal/kg/day) and a protein intake of 0.6 in predialysis and 1.2 g/kg in dialysis population to prevent PEW.[19],[20]

Any increase in protein and carbohydrate results in concomitant increase in potassium or phosphorus in the diet which have to be restricted to prevent hyperkalemia and hyperphosphatemia. Chronic hyperphosphatemia causes secondary hyperparathyroidism, renal osteodystrophy, and cardiovascular calcification; therefore, reduction of phosphorus intake to 10–12 mg/g protein for HD patients is recommended.[21] Recommending low-phosphorus products limits protein intake, which is contraindicated in patients on RRT and also decreases the patient's quality of life. However, it is more appropriate to relax restrictions and accepts a more balanced and individualized approach in CKD patients.[22] Fiber requirement of CKD patients is 15 g/1000 kcal which is the same as that for the general population. Fiber intake can be increased to 25 g/day.[23]

Studies have shown that 97% of HD patients consume <25 g of dietary fiber per day. Another study has revealed that dialysis patients present a lower intake of Vitamin C and the carotenoids lycopene, cryptoxanthin, and lutein than controls.[24] Dietary recommendations for CKD stage 3–5D patients emphasize on potassium restriction, which is present in abundance in fruits and vegetables. However, in the face of elevated oxidative stress and increased cardiovascular risk, eliminating the sources of antioxidants, i.e., fruits and vegetables may be aggravating oxidative stress, inflammation, and infection. In CKD, oral supplements can help achieve nutritional objectives. Substitution of amino acids for dextrose in the PD fluid and the provision of parenteral nutrition during HD sessions (IDPN although controversial) can improve hypoalbuminemia and hence, nutritional status.[25],[26]

Patients who are unable to meet protein/energy requirements with food for an extended period of time should be given nutrition support. The extended period was from days to 2 weeks. However, guidelines recommend that complete nutritional assessment is needed before intervention to eliminate/treat any potentially reversible or treatable condition or medication that might interfere with appetite or cause malnutrition. In severely malnourished patients tube feeding should be offered if oral nutrition is inadequate. However, if tube feeding cannot be used (patient is unwilling or is not hospitalized), IDPN for HD and IPAA for PD should be considered. IDPN should be initiated if spontaneous intake is >20 kcal/kg/IBW and 0.8 g protein/kg/IBW. Total parenteral nutrition should be considered if spontaneous intake is <20 kcal/kg/IBW and 0.8 g protein/kg/IBW (combination of oral and IDPN is insufficient). Sodium, potassium, and magnesium may be added to the solution as per the patient's requirement.[27] Efficacy of nutritional support can be improved with exercise, anabolic agents, adequate dialysis, appetizers, and intradialysis compulsory meals. Early treatment of infections, good water quality, and adequate management of cardiovascular disease are important factors in all over the management of MIA syndrome. The uses of prebiotics and probiotics in the management of chronic inflammation are new areas of therapy. The gut microbiota as a source of inflammation in CKD patients has been proposed as some of these flora are responsible for “leaky gut” in CKD.[28],[29],[30],[31],[32]

Mediterranean diet is characterized by low to moderate consumption of animal protein and proportionally high consumption of fruits, vegetables, bread, beans, nuts, seeds and other cereals. This diet has been associated with reduced risk of cardiovascular disease. It is rich in antioxidants and has anti-inflammatory qualities, yet advocating liberal intake of fruits, vegetables and nuts can put the patient at risk of developing hyperkalemia and hyperphsphatemia if the patient is on twice weekly dialysis regime. However, patients in early CKD stages with good urine output may benefit from Mediterranean diet provided low potassium fruits and vegetables are advised and serum phosphate is within normal reference range (nuts usually have high phosphorus content). Other nutrients that are equally important for reducing inflammation are vitamin D, magnesium, and zinc. Vitamin D modulates the immune system through the VDR receptor in the cell nucleus; however, its activation is impaired when kidney function declines. Magnesium, in turn, takes part in numerous enzymatic processes, suppresses inflammation, and is inversely associated with CRP levels [33],[34],[35] Magnesium can accumulate in the body in stage 5 CKD patients. Zinc is a cofactor for many enzymes, and its deficiency may influence the production of T lymphocytes taking part in the immune response [36], hence supplement zinc if its deficiency is documented. Use of HYPERLINK “https://www.sciencedirect.com/topics/medicine-and-dentistry/anabolic-agent”anabolic steroids is well established but often it has limited efficacy and not without compliance problems and adverse effects.[37]

  Conclusion Top

Malnutrition, inflammation, and atherosclerosis are common problems in HD patients, and the prevalence varies widely between 20% and 60%.[37] A single measure of elevated serum CRP is a strong predictor of mortality, and higher levels are associated with worse outcomes.[15] The prevention of MIA syndrome is of utmost importance because the emergence of each of its components worsens the survival potential of ESRD patients. Majority of ESRD patients have the signs of atherosclerosis.[3],[14],[15] Therefore, the predialysis period is the ideal time to start therapeutic interventions.[16]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Kaysen GA, Stevenson FT, Depner TA. Determinants of albumin concentration in hemodialysis patients. Am J Kidney Dis 1997;29:658-68.  Back to cited text no. 1
Yeun JY, Kaysen GA. Acute phase proteins and peritoneal dialysate albumin loss are the main determinants of serum albumin in peritoneal dialysis patients. Am J Kidney Dis 1997;30:923-7.  Back to cited text no. 2
Bergström J, Heimbürger O, Lindholm B, Qureshi AR. Elevated serum C-reactive protein is a strong predictor of increased mortality and low serum albumin in hemodialysis (HD) patients. J Am Soc Nephrol 1995;6:573.  Back to cited text no. 3
Bologa RM, Levine DM, Parker TS, Cheigh JS, Serur D, Stenzel KH, et al. Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis 1998;32:107-14.  Back to cited text no. 4
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-9.  Back to cited text no. 5
Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke 1999;30:981-5.  Back to cited text no. 6
Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391-8.  Back to cited text no. 7
Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH Jr., et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999;106:506-12.  Back to cited text no. 8
Stenvinkel P, Heimbürger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899-911.  Back to cited text no. 9
Kim WS, Lee DH, Youn HJ. Calcium-phosphorus product concentration is a risk factor of coronary artery disease in metabolic syndrome. Atherosclerosis 2013;229:253-7.  Back to cited text no. 10
Stenvinkel P, Heimbürger O, Lindholm B, Kaysen GA, Bergström J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000;15:953-60.  Back to cited text no. 11
Zyga S, Christopoulou G, Maria. Malliarou Malnutrition-inflammation-atherosclerosis syndrome in patients with end-stage renal disease Journal of Renal Care 2011;37:12-5.  Back to cited text no. 12
Pecoits-Filho R, Lindholm B, Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome – The heart of the matter. Nephrol Dial Transplant 2002;17 Suppl 11:28-31.  Back to cited text no. 13
Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-58.  Back to cited text no. 14
Iseki K, Tozawa M, Yoshi S, Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999;14:1956-60.  Back to cited text no. 15
Hamer RA, El Nahas AM. The burden of chronic kidney disease. BMJ 2006;332:563-4.  Back to cited text no. 16
Rajapurkar MM, John GT, Kirpalani AL, Abraham G, Agarwal SK, Almeida AF, et al. What do we know about chronic kidney disease in India:First report of the Indian CKD registry. BMC Nephrol 2012;13:10.  Back to cited text no. 17
Kirushnan BB, Rao BS, Annigeri R, Balasubramanian S, Seshadri R, Prakash KC, et al. Impact of Malnutrition, Inflammation, and Atherosclerosis on the Outcome in Hemodialysis Patients. Indian J Nephrol 2017;27:277-83.  Back to cited text no. 18
[PUBMED]  [Full text]  
NKF/ KDOQI clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis 2000;35 Suppl 2.  Back to cited text no. 19
Maraj M, Kuśnierz-Cabala B, Dumnicka P, Gala-Błądzińska A, Gawlik K, Pawlica-Gosiewska D, et al. Malnutrition, Inflammation, Atherosclerosis syndrome (MIA) and diet recommendations among end-stage renal disease patients treated with maintenance hemodialysis. Nutrients 2018;10. pii: E69.  Back to cited text no. 20
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:S1-201.  Back to cited text no. 21
Kalantar-Zadeh K, Tortorici AR, Chen JL, Kamgar M, Lau WL, Moradi H, et al. Dietary restrictions in dialysis patients: Is there anything left to eat? Semin Dial 2015;28:159-68.  Back to cited text no. 22
Khoueiry G, Waked A, Goldman M, El-Charabaty E, Dunne E, Smith M, et al. Dietary intake in hemodialysis patients does not reflect a heart healthy diet. J Ren Nutr 2011;21:438-47.  Back to cited text no. 23
Kalantar-Zadeh K, Kopple JD, Deepak S, Block D, Block G. Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire. J Ren Nutr 2002;12:17-31.  Back to cited text no. 24
Anita S, Sharma RK. Randomized controlled trial on effect of intradialytic parenteral nutrition (IDPN) on malnourished dialysis dependent patients. J Renal Nutr Metab 2015;1:121-7.  Back to cited text no. 25
Anita S. Intradialytic parenteral nutritional supplementation for prevention of muscle mass. Editorial J Renal Nutr Metab 2016;2:vii.  Back to cited text no. 26
Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, National Kidney Foundation. Am J Kidney Dis 2000;35:S1-140.  Back to cited text no. 27
Borges NA, Carmo FL, Stockler-Pinto MB, de Brito JS, Dolenga CJ, Ferreira DC, et al. Probiotic Supplementation in Chronic Kidney Disease: A Double-blind, Randomized, Placebo-controlled Trial. J Ren Nutr 2018;28:28-36.  Back to cited text no. 28
Moraes C, Borges NA, Mafra D. Resistant starch for modulation of gut microbiota: Promising adjuvant therapy for chronic kidney disease patients? Eur J Nutr 2016;55:1813-21.  Back to cited text no. 29
Mafra D, Fouque D. Gut microbiota and inflammation in chronic kidney disease patients. Clin Kidney J 2015;8:332-4.  Back to cited text no. 30
Barros AF, Borges NA, Ferreira DC, Carmo FL, Rosado AS, Fouque D, et al. Is there interaction between gut microbial profile and cardiovascular risk in chronic kidney disease patients? Future Microbiol 2015;10:517-26.  Back to cited text no. 31
Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Zeimbekis A, Kastorini CM, et al. Adherence to the Mediterranean diet is associated with renal function among healthy adults: The ATTICA study. J Ren Nutr 2010;20:176-84.  Back to cited text no. 32
Hoe E, Nathanielsz J, Toh ZQ, Spry L, Marimla R, Balloch A, et al. Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection. Nutrients 2016;8. pii: E806.  Back to cited text no. 33
Dibaba DT, Xun P, He K. Corrigendum. Dietary magnesium intake is inversely associated with serum C-reactive protein levels: Meta-analysis and systematic review. Eur J Clin Nutr 2015;69:410.  Back to cited text no. 34
Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients 2017;9. pii: E624.  Back to cited text no. 35
Fouque D, Laville M, Guebre-Egziabher F. Advances in anabolic interventions for malnourished dialysis patients Journal of Renal Nutrition 2003;13:161-5.  Back to cited text no. 36
de Mutsert R, Grootendorst DC, Boeschoten EW, Brandts H, van Manen JG, Krediet RT, et al. Subjective global assessment of nutritional status is strongly associated with mortality in chronic dialysis patients. Am J Clin Nutr 2009;89:787-93.  Back to cited text no. 37


  [Figure 1]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
What is Malnutri...
Challenges in th...
Management of Ma...
Article Figures

 Article Access Statistics
    PDF Downloaded29    
    Comments [Add]    

Recommend this journal