Emerging cross-talks between chronic kidney disease–mineral and bone disorder (CKD–MBD) and malnutrition–inflammation complex syndrome (MICS) in patients receiving dialysis

Abstract

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is a systemic disorder that affects multiple organs and systems and increases the risk of morbidity and mortality in patients with CKD, especially those receiving dialysis therapy. CKD–MBD is highly prevalent in CKD patients, and its treatment is gaining attention from healthcare providers who manage these patients. Additional important pathologies often observed in CKD patients are chronic inflammation and malnutrition/protein-energy wasting (PEW). These two pathologies coexist to form a vicious cycle that accelerates the progression of various other pathologies in CKD patients. This concept is integrated into the term “malnutrition–inflammation–atherosclerosis syndrome” or “malnutrition–inflammation complex syndrome (MICS)”. Recent basic and clinical studies have shown that CKD–MBD directly induces inflammation as well as malnutrition/PEW. Indeed, higher circulating levels of inorganic phosphate, fibroblast growth factor 23, parathyroid hormone, and calciprotein particles, as markers for critical components and effectors of CKD–MBD, were shown to directly induce inflammatory responses, thereby leading to malnutrition/PEW, cardiovascular diseases, and clinically relevant complications. In this short review, we discuss the close interplay between CKD–MBD and MICS and emphasize the significance of simultaneous control of these two seemingly distinct pathologies in patients with CKD, especially those receiving dialysis therapy, for better management of the CKD/hemodialysis population.

Muscle Wasting in Chronic Kidney Disease: Mechanism and Clinical Implications—A Narrative Review

“…Current evidence has shown that several complications associated with CKD contribute to dysregulated muscle protein balance, including anemia, metabolic acidosis, abnormal growth hormone axis and androgen deficiencies, insulin resistance, inflammation, hemodialysis (HD) process, and disuse [ 4 ], exhibiting varying extents from early CKD to dialysis [ 5 ]. Other studies have indicated that CKD-related mineral and bone disorders also involve in the development of muscle wasting in CKD [ 6 ], including vitamin D deficiency [ 7 ] and secondary hyperparathyroidism [ 8 ]. The complex interactions of these CKD factors and pathophysiological changes at the cellular level have been explored [ 9 , 10 , 11 ], but remain poorly understood.…”

An updated clinical prediction model of protein-energy wasting for hemodialysis patients

“…It is hydroxylated to 25-hydroxyvitamin D 3 (25-OHD 3 ) in the liver and further hydroxylated to biologically active 1,25-(OH) 2 D 3 via the enzyme 1-α-hydroxylase ( 44 ). CKD–MBD is prevalent in CKD patients, and high levels of PTH can induce the hydroxylation of 25-OHD 3 to 1,25-(OH) 2 D 3 ( 16 ). The biologically active 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) exerts its muscle differentiation and proliferation functions through binding with vitamin D receptor (VDR) ( 44 ).…”

“…Furthermore, inflammation can lead to adipose tissue browning, muscle atrophy, and increased resting energy expenditure (REE), which ultimately lead to PEW (15). Recent basic and clinical studies demonstrate that chronic kidney disease-mineral and bone disorder (CKD-MBD) directly induces inflammation and PEW, and high circulating levels of parathyroid hormone (PTH) have been proven to induce the inflammatory response that leads to PEW (16). PTH can also increase adipose tissue browning and REE, which explains the clinical association between secondary hyperparathyroidism and PEW in hemodialysis patients (17)(18)(19)(20).…”

Comparison of nutrition screening tools in patients receiving maintenance hemodialysis

“…3 Additionally, we have also recently developed another multifaceted and objective scoring system, named simple MICS score, as it is calculated through a combination of age, serum levels of albumin, Cr, and C-reactive protein, and BMI stratified by sex. 4 Although these newly developed scores are presumed to be good surrogates of MIS, few studies have validated those scoring systems with the MIS, a gold standard tool.To determine the association of the MIS with other surrogate markers of nutritional status, including the simple MICS score and the NRI-JH, we conducted a crosssectional study comprising 72 patients receiving maintenance hemodialysis at a single center. Their mean age was 71 years, 58% were male, 39% had diabetic nephropathy, and the median dialysis vintage was 7.5 years.…”

“…3 Additionally, we have also recently developed another multifaceted and objective scoring system, named simple MICS score, as it is calculated through a combination of age, serum levels of albumin, Cr, and C-reactive protein, and BMI stratified by sex. 4 Although these newly developed scores are presumed to be good surrogates of MIS, few studies have validated those scoring systems with the MIS, a gold standard tool.…”