Functional Gastroenterology Bolus: Does It Start in the Gut? Relationships Between the GI Tract and Chronic Kidney Disease.
CKD may be caused by poorly controlled hypertension or diabetes and by autoimmune conditions such as lupus erythematosus. A factor often underlying the "essential hypertension" is intestinal dysbiosis (Ahmadmehrabi, 2017). CKD patients have altered flora marked by significantly lower Bifidobacteria, Lactobacillus, and Prevotella genera and increased Clostridium perfringens and Enterobacteriaceae (Sampaio-Maia, 2016). Altered intestinal flora trigger gastrointestinal and systemic inflammation and hyperpermeability. The hyperpermeability stretches from the stomach to the colon allowing for increased lipopolysaccharide absorption and bacterial translocation (Vaziri, 2012) (Vaziri, 2013).
In addition, these increases in permeability allow higher absorption of protein fermentation (putrification) products such as indole from tryptophan, phenol from tyrosine and phenylalanine, and trimethylamine from choline and carnitine (Rossi, 2014). Once absorbed systemically, hepatocytes convert these into indoxyl sulfate, p-cresol sulfate and triethylamine-N-oxide (Stubbs JR, 2016 & Missailidis C, 2016). These three compounds are renotoxic and cardiotoxic due in part to the promotion of endothelial dysfunction. Endothelial cells typically elaborate antithrombotic, anti-inflammatory and vasodilatory substances. In endothelial dysfunction, there is a shift to prothrombotic, pro-inflammatory and vasoconstrictive patterns (Kumar, 2010).
Cytokines rise and as the intestinal protein metabolites increase, there is insulin resistance, suppression of erythropoiesis, premature cellular senescence, activation of the renin-angiotensin-aldosterone system, and enhanced atherogenesis, and vascular calcification (Rossi, 2014).
In addition, there is a decrease in short chain fatty acids (SCFA), which leads to an increase in hepatic lipogenesis and gluconeogenesis--fueling the insulin resistance and metabolic syndrome (Scorletti, 2016). Cardiovascular disease, fatty liver, and more advanced chronic renal disease become more likely. SCFAs, when present in sufficient quantities, regulate PPAR gamma as well as increasing incretin production in gut enteroendocrine cells. This allows a shift in metabolism to increased lipid synthesis and decreased beta-oxidation. Decreased SCFAs promote fatty liver and hepatic insulin resistance (Higashimura, 2015). Type 2 diabetes may ensue if the necessary hereditary, dietary (high fructose corn syrup, high carbohydrate diet) and environmental factors (persistent organic pollutants) are present.
Rather than "watchful waiting" in the setting of dysbiosis, is it not best to be proactive as early as possible and educate the patient when in the earliest stages of chronic kidney disease? Options for prevention of CKD progression include the following:
* Treat small intestinal bacterial overgrowth when present and balance Gl flora as needed (Strid, 2003);
* Modify protein intake - vegans and vegetarians have lower circulating TMAO levels, PCS and IS compared to omnivores (Koeth, 2013) (Patel, 2012);
* Modify carbohydrate intake with gluten or grain-free diets such as the specific carbohydrate, low FODMAPs or SIBO specific food guide. Increase soluble fiber if tolerated using foods such as inulin, flax, chia, psyllium, vegetable fiber (Rossi, 2015);
* Use of probiotic supplements such as Lactobacillus reuteri (Rossi. 2015);
* Balance cortisol/DHEA levels;
* Employ properly prescribed botanical medicines: Cordyceps sinensis, Rheum palmatum (Guan, 2015), Astragalus membranaceus, Salvia miltiorrhiza (Danshen), Angelica sinensis (dong quai) (Hsieh, 2017) and Portulaca oleracea (purslane) (Iranshahy, 2017) These herbs may prove useful in preventing progression of chronic kidney disease;
* Recommend moderate daily exercise such as walking; and
* Improve sleep hygiene to promote 7-8 hours of quality sleep per night.
Ahmadmehrabi S, Tang WHW. (2017). Gut microbiome and its role in cardiovascular diseases. Curr Opm Cardiol. 32(6):761-766.
Guan, Y. (201S). Effects and Mechanism of Combination of Rhein and Danshensu in the Treatment of Chronic Kidney Disease. Am J Chin Med. 43(7):1381-400.
Higashimura, Y. (2015). Propionate Promotes Fatty Acid Oxidation through the Up-Regulation of Peroxisome Proliferator-Activated Receptor [alpha] in Intestinal Epithelial Cells. J Nutr Sci Vitaminol (Tokyo). 61(6):511-5.
Hsieh, C. (2017). Prescribed Renoprotective Chinese Herbal Medicines Were Associated with a Lower Risk of All-Cause and Disease-Specific Mortality among Patients with Chronic Kidney Disease: A Population-Based Follow-Up Study in Taiwan. Evid Based Complement Alternat Med. 2017;5632195.
Iranshahy, M. (2017). A review of traditional uses, phytochemistry and pharmacology of Portulaca oleracea L. J Ethnopharmacol. 205:158-172.
Koeth, R. (2013). Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 19(5):576-85.
Kumar, V. (2010). Pathologic Basis of Disease. In V. Kumar, Pathologic Basis of Disease (pp. 490-491). Philadelphia, PA: Saunders.
Missailidis C. (2016). Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease. PioS One. 2016 Jan ll;ll(l):e0141738.
Patel, K. (2012). The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. Clin J Am Soc Nephrol. 7(6):982-8.
Rossi. (2015). The Kidney-Gut Axis: Implications for Nutrition Care. J Ren Nutr. 25(5):399-403.
Rossi, M. (2014). Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study. Nutr Metab Cardiovasc Dis. Nutr Metab Cardiovasc Dis. 24(9):1035-42.
Sampaio-Maia, B. (2016). The Role of the Gut Microbiome on Chronic Kidney Disease. Adv Appl Microbiol. 96:65-94.
Scorletti, E. Byrne CD. (2016). Extrahepatic Diseases and NAFLD: The Triangular Relationship Between NAFLD, Type 2 Diabetes, and Dysbiosis. Dig Dis. 2016;34 Suppl 1;11-18.
Strid, H. (2003). Patients with chronic renal failure have abnormal small intestinal motility and a high prevalence of small intestinal bacterial overgrowth. Digestion. 67(3):129-37.
Stubbs JR et al. (2016). Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden. J Am Soc Nephrol. 27(1):305-13.
Vaziri, N. (2012). Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol. 36(5):438-43.
Vaziri, N. (2013). Chronic Kidney disease disrupts gastric and small intestine tight junctions. Am J Nephrol. 38(2):99-103.
by Steven Sandberg-Lewis, ND, DHANP
Steven Sandberg-Lewis, ND, has been practicing since 1978, teaching gastroenterology at National University of Natural Medicine and in private practice at 8 Hearts Health and Wellness in Portland, Oregon. He lectures, presents webinars and interviews on issues of digestive health. He is the author of the medical textbook Functional Gastroenterology: Assessing and Addressing the Causes of Functional Digestive Disorders, Second Edition, 2017. Within gastroenterology, he has special interest and expertise in inflammatory bowel disease (including microscopic colitis), irritable bowel syndrome (including post-infectious IBS), Small Intestine Bacterial Overgrowth (SIBO), hiatal hernia, gastroesophageal and bile reflux (GERD), biliary dyskinesia, and chronic states of nausea and vomiting.
Dr. Sandberg-Lewis lives in Portland with his wife, Kayle. His interests include mandolin, guitar, writing, and lecturing.
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|Date:||Jan 1, 2018|
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