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| FROM EDITOR’S DESK |
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| Year : 2019 | Volume
: 5
| Issue : 3 | Page : 57-58 |
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Latency and crescendo of uremic Milieu
Anita Saxena
Editor, JRNM, Professor; Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| Date of Submission | 02-Feb-2020 |
| Date of Acceptance | 02-Feb-2020 |
| Date of Web Publication | 17-Feb-2020 |
Correspondence Address:
Dr. Anita Saxena
Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jrnm.jrnm_2_20
How to cite this article:
Saxena A. Latency and crescendo of uremic Milieu. J Renal Nutr Metab 2019;5:57-8 |
Preventing protein–energy wasting is a challenging task in chronic kidney disease (KD). It was in the 1930s that Rudolph Schoenheimer discovered that skeletal muscle is in a state of continual turnover. In a normal adult, 3.5–4.5 g protein/kg body weight is synthesized and degraded each day, and the majority of these proteins are intracellular proteins.[1] Simple mathematics implies that in a healthy human weighing 70 kg and consuming 1 g/kg/day of protein, 280 g of protein is synthesized every day which is four times the body weight. However, when catabolic conditions are present, skeletal muscle is degraded at an accelerated rate. In chronic KD, to a certain extent, treatment outcome and mortality are related to loss of muscle mass, which springs two questions: (i) how are protein stores lost? and (ii) how can the losses be prevented? Loss of muscle protein stores can result from three major responses, namely, (i) impaired growth of new muscle fibers, (ii) suppression of protein synthesis, and (iii) stimulation of protein degradation. In chronic KD, reduction in protein pool stores begins with uremia-induced protein breakdown on account of loss of appetite, taste, and smell, leading to decreased food intake; elevated levels of uremic toxins such as middle molecules and leptin; reduced levels of ghrelin; growth hormone synthesis; impaired insulin-like growth factor 1 axis; acidemia; increased insulin resistance; decreased insulin sensitivity; increased cortisol, aldosterone, and angiotensin II; and increased cytokine levels, which emerge from uremic milieu and trigger aforementioned major responses.
To compound this effect, chronic KD impairs intestinal barrier function, which leads to endotoxemia and systemic inflammation.[2] The gut–microbiota dysbiosis, which has emerged as an important modifiable nontraditional risk factor for the origination of cardiovascular disease and of progression of chronic KD,[3] also indirectly causes muscle protein breakdown (muscle wasting) by boosting the formation of uremic toxins and chronic inflammation. The human gut harbors >100 trillion microbial cells, which influence nutrition, metabolism, physiology, and immune function of the host. On one hand, uremia induces oxidative stress and inflammation and on the other hand impairment of intestinal barrier function increases intestinal permeability to high-molecular-weight polyethylene glycols contributing to the prevailing inflammation,[4],[5],[6] furthering renal insult (“the gut–kidney axis” theory and “the chronic KD–colonic axis”). An early trigger of inflammation is translocation of gut microbiota, particularly endotoxins or lipopolysaccharides on the surface of Gram-negative bacteria to the systemic circulation by signaling through toll-like receptor 4 on phagocytic cells of the immune system.[4] Several mechanisms alter the biochemical milieu of the gastrointestinal tract (GIT). The Folin's laws[7] (1905) on human urine composition pointed out that “the principal metabolic response to an increase or a decrease in dietary protein content is a parallel change in urea excretion.” Imbalanced protein intake with respect to kidney health causes high urea concentration in the intracellular and extracellular fluids, which spearheads its (urea) influx into GIT, diffusing into glandular secretions. Hydrolysis of urea by urease causes formation of large quantities of ammonia, leading to modification of the luminal pH and causing uremic enterocolitis.[8] Hence, targeting microbiota by preventing gut leakiness and prescribing low-protein intake coupled with the supplementation of essential aminoacid analogs, prebiotics, probiotics, and synbiotics for timely digestion of protein may control the formation of uremic toxins and consequently control inflammation and disease progression and preserve muscle proteins.
In this issue, two articles, one on “pathophysiology of protein energy wasting-mini review” and the other on “metabolic implications of peritoneal dialysis-classroom reading,” touch upon decreased body stores of protein in chronic KD.
| References | |  |
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| 2. | Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol 2013;37:1-6. |
| 3. | Kang JY. The gastrointestinal tract in uremia. Dig Dis Sci 1993;38:257-68. |
| 4. | Cosola C, Rocchetti MT, Sabatino A, Fiaccadori E, Di Iorio BR, Gesualdo L. Microbiota issue in CKD: How promising are gut-targeted approaches? J Nephrol 2019;32:27-37. |
| 5. | Vaziri ND, Dure-Smith B, Miller R, Mirahmadi MK. Pathology of gastrointestinal tract in chronic hemodialysis patients: An autopsy study of 78 cases. Am J Gastroenterol 1985;80:608-11. |
| 6. | Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: Evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 2007;86:1286-92. |
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| 8. | Vaziri ND, Wong J, Pahl M, Piceno YM, Yuan J, DeSantis TZ, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013;83:308-15. |
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