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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
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrnm.jrnm_56_19

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  Abstract 


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 Jan 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

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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]

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Conflicts of interest

There are no conflicts of interest.



 
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