Hypertension in Chronic Kidney Disease: Novel Insights

Author(s): Anila Duni, Evangelia Dounousi, Paraskevi Pavlakou, Theodoros Eleftheriadis, Vassilios Liakopoulos*.

Journal Name: Current Hypertension Reviews

Volume 16 , Issue 1 , 2020

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Graphical Abstract:


Management of arterial hypertension in patients with chronic kidney disease (CKD) remains a major challenge due to its high prevalence and associations with cardiovascular disease (CVD) and CKD progression. Several clinical trials and meta-analyses have demonstrated that aggressive treatment of hypertension in patients with and without CKD lowers the risk of CVD and all-cause mortality, nevertheless the effects of blood pressure (BP) lowering in terms of renal protection or harm remain controversial. Both home and ambulatory BP estimation have shown that patients with CKD display abnormal BP patterns outside of the office and further investigation is required, so as to compare the association of ambulatory versus office BP measurements with hard outcomes and adjust treatment strategies accordingly. Although renin-angiotensin system blockade appears to be beneficial in patients with advanced CKD, especially in the setting of proteinuria, discontinuation of renin-angiotensin system inhibition should be considered in the setting of frequent episodes of acute kidney injury or hypotension while awaiting the results of ongoing trials. In light of the new evidence in favor of renal denervation in arterial hypertension, the indications and benefits of its application in individuals with CKD need to be clarified by future studies. Moreover, the clinical utility of the novel players in the pathophysiology of arterial hypertension and CKD, such as microRNAs and the gut microbiota, either as markers of disease or as therapeutic targets, remains a subject of intensive research.

Keywords: Arterial hypertension, chronic kidney disease, ambulatory blood pressure monitoring, renal denervation, microRNAs, gut microbiota.

Muntner P, Anderson A, Charleston J, et al. Hypertension awareness, treatment, and control in adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 2010; 55: 441-51.
Chang AR, Appel LJ. Target blood pressure for cardiovascular disease prevention in patients with CKD. Clin J Am Soc Nephrol 2018; 13(10): 1572-4.
Chang TI, Sarnak MJ. Intensive blood pressure targets and kidney disease. Clin J Am Soc Nephrol 2018; 13(10): 1575-7.
Sinha AD, Agarwal R. The complex relationship between CKD and ambulatory blood pressure patterns. Adv Chronic Kidney Dis 2015; 22(2): 102-7.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/ PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Hypertension 2018; 71(6): 1269-324.
Wright JT Jr, Williamson JD, Whelton PK, et al. SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373: 2103-16.
Soliman EZ, Ambrosius WT, Cushman WC, et al. SPRINT Research Study Group. Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: SPRINT (Systolic Blood Pressure Intervention Trial). Circulation 2017; 136(5): 440-50.
Paoletti E, De Nicola L, Gabbai FB, et al. Associations of left ventricular hypertrophy and geometry with adverse outcomes in patients with CKD and hypertension. Clin J Am Soc Nephrol 2016; 11(2): 271-9.
Papademetriou V, Zaheer M, Doumas M, et al. ACCORD Study Group. Cardiovascular outcomes in action to control cardiovascular risk in diabetes: Impact of blood pressure level and presence of kidney disease. Am J Nephrol 2016; 43: 271-80.
Malhotra R, Nguyen HA, Benavente O, et al. Association between more intensive vs. less intensive blood pressure lowering and risk of mortality in chronic kidney disease stages 3 to 5: A systematic review and meta-analysis. JAMA Intern Med 2017; 177(10): 1498-505.
Beddhu S, Rocco MV, Toto R, et al. SPRINT Research Group. Effects of intensive systolic blood pressure control on kidney and cardiovascular outcomes in persons without kidney disease: A secondary analysis of a randomized trial. Ann Intern Med 2017; 167: 375-83.
Cheung AK, Rahman M, Reboussin DM, et al. SPRINT Research Group. Effects of intensive BP control in CKD. J Am Soc Nephrol 2017; 28: 2812-23.
Tsai WC, Wu HY, Peng YS, et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: A systematic review and meta-analysis. JAMA Intern Med 2017; 177(6): 792-9.
Beddhu S, Greene T, Boucher R, et al. Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials. Lancet Diabetes Endocrinol 2018; 6(7): 555-63.
Rocco MV, Sink KM, Lovato LC, et al. SPRINT Research Group. Effects of intensive blood pressure treatment on acute kidney injury events in the Systolic Blood Pressure Intervention Trial (SPRINT). Am J Kidney Dis 2018; 71(3): 352-61.
Ku E, Bakris G, Johansen KL, et al. Acute Declines in Renal Function during Intensive BP Lowering: Implications for Future ESRD Risk. Am Soc Nephrol 2017; 28(9): 2794-801.
Ku E, Ix JH, Jamerson K, et al. Acute declines in renal function during intensive BP lowering and long-term risk of death. J Am Soc Nephrol 2018; 29(9): 2401-8.
Malhotra R, Craven T, Ambrosius WT, et al. SPRINT Research Group. Effects of intensive blood pressure lowering on kidney tubule injury in CKD: A longitudinal subgroup analysis in SPRINT. Am J Kidney Dis 2018; pii: S0272-6386(18): 30879-5.
Nadkarni GN, Chauhan K, Rao V, et al. Effect of intensive blood pressure lowering on kidney tubule injury: Findings from the ACCORD trial study participants. Am J Kidney Dis 2018; pii: S0272-6386 (18): 30880-1.
Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-104.
Mancia G. Target blood pressure and kidney protection. Lancet Diabetes Endocrinol 2018; 6(7): 521-3.
Banegas JR, Ruilope LM, de la Sierra A, et al. High prevalence of masked uncontrolled hypertension in people with treated hypertension. Eur Heart J 2014; 35: 3304-12.
Banegas JR, Ruilope LM, de la Sierra A, et al. Relationship between clinic and ambulatory blood-pressure measurements and mortality. N Engl J Med 2018; 378: 1509-20.
Drawz PE, Pajewski NM, Bates JT, et al. Effect of intensive versus standard clinic-based hypertension management on ambulatory blood pressure: Results from the SPRINT (systolic blood pressure intervention trial) ambulatory blood pressure study. Hypertension 2017; 69: 42-50.
McManus RJ, Mant J, Franssen M, et al. TASMINH4 investigators. Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): An unmasked randomised controlled trial. Lancet 2018; 391(10124): 949-59.
Drawz PE, Alper AB, Anderson AH, et al. Chronic Renal Insufficiency Cohort Study Investigators. Masked hypertension and elevated nighttime blood pressure in CKD: Prevalence and association with target organ damage. Clin J Am Soc Nephrol 2016; 11: 642-52.
Tang H, Gong WY, Zhang QZ, et al. Prevalence, determinants, and clinical significance of masked hypertension and white-coat hypertension in patients with chronic kidney disease. Nephrology (Carlton) 2016; 21: 841-50.
Thomas G, Drawz PE. BP measurement techniques: What they mean for patients with kidney disease. Clin J Am Soc Nephrol 2018; 13(7): 1124-31.
Velasquez MT, Beddhu S, Nobakht E, Rahman M, Raj DS. Ambulatory blood pressure in chronic kidney disease: Ready for prime time? Kidney Int Rep 2016; 1(2): 94-104.
Salman IM, Hildreth CM, Ameer OZ, Phillips JK. Differential contribution of afferent and central pathways to the development of baroreflex dysfunction in chronic kidney disease. Hypertension 2014; 63: 804-10.
Isobe S, Ohashi N, Fujikura T, et al. Disturbed circadian rhythm of the intrarenal renin angiotensin system: Relevant to nocturnal hypertension and renal damage. Clin Exp Nephrol 2015; 19: 231-9.
Dhaun N, Moorhouse R, MacIntyre IM, et al. Diurnal variation in blood pressure and arterial stiffness in chronic kidney disease: The role of endothelin-1. Hypertension 2014; 64: 296-304.
Duni A, Liakopoulos V, Rapsomanikis KP, Dounousi E. Chronic kidney disease and disproportionally increased cardiovascular damage: Does oxidative stress explain the burden? Oxid Med Cell Longev 2017; 2017:9036450
Minutolo R, Gabbai FB, Agarwal R, et al. Assessment of achieved clinic and ambulatory blood pressure recordings and outcomes during treatment in hypertensive patients with CKD: A multicenter prospective cohort study. Am J Kidney Dis 2014; 64: 744-52.
Wang C, Zhang J, Li Y, et al. Masked hypertension, rather than white-coat hypertension, has a prognostic role in patients with non-dialysis chronic kidney disease. Int J Cardiol 2017; 230: 33-9.
Katafuchi E, Nakayama M, Tanaka S, et al. Comparison of prognostic values of daytime and night-time systolic blood pressures on renal outcomes in patients with chronic kidney disease. Circ J 2017; 81(10): 1454-62.
Scheppach JB, Raff U, Toncar S, et al. Blood pressure pattern and target organ damage in patients with chronic kidney disease. Hypertension 2018; 72(4): 929-36.
Paoletti E, De Nicola L, Gabbai FB, et al. Associations of left ventricular hypertrophy and geometry with adverse outcomes in patientswith CKD and hypertension. Clin J Am Soc Nephrol 2016; 11(2): 271-9.
Park M, Hsu CY, Li Y, et al. Chronic Renal Insufficiency Cohort (CRIC) Study Group. Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 2012; 23(10): 1725-34.
Ioannou K, Stel VS, Dounousi E, et al. Inflammation, endothelial dysfunction and increased left ventricular mass in chronic kidney disease (CKD) patients: A longitudinal study. PLoS One 2015; 10(9)e0138461
Spoto B, Ntounousi E, Testa A, et al. The sirtuin1 gene associates with left ventricular myocardial hypertrophy and remodeling in two chronic kidney disease cohorts: A longitudinal study. J Hypertens 2018; 36(8): 1705-11.
Dounousi E, Bouba I, Spoto B, et al. A genetic biomarker of oxidative stress, the paraoxonase 1 Q192R gene variant, associates with cardiomyopathy in CKD: A longitudinal study. Oxid Med Cell Longev 2016; 2016:1507270
Stel VS, Ioannou K, Brück K, et al. Longitudinal association of body mass index and waist circumference with left ventricular mass in hypertensive predialysis chronic kidney disease patients. Nephrol Dial Transplant 2013; 28(Suppl. 4): iv136-45.
Olsen MH, Angell SY, Asma S, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: The Lancet Commission on hypertension. Lancet 2016; 388(10060): 2665-71.
Nwankwo T, Yoon SS, Burt V, Gu Q. Hypertension among adults in the United States: National Health and Nutrition Examination Survey, 2011-2012. NCHS Data Brief 2013; 133: 1-8.
Di Daniele N, Fegatelli DA, Rovella V, Castagnola V, Gabriele M, Scuteri A. Circadian blood pressure patterns and blood pressure control in patients with chronic kidney disease. Atherosclerosis 2017; 267: 139-45.
Kuczera P, Kwiecień K, Adamczak M, et al. Relevance of peripheral, central or nighttime blood pressure measurements in the prediction of chronic kidney disease progression in patients with mild or no-proteinuria. Kidney Blood Press Res 2018; 43(3): 735-43.
Drawz PE, Brown R, De Nicola L, et al. CRIC Study Investigators. Variations in 24-hour BP profiles in cohorts of patients with kidney disease around the world: The I-DARE study. Clin J Am Soc Nephrol 2018; 13(9): 1348-57.
Tripepi G, Fagugli RM, Dattolo P, et al. Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/ day ratio in nondiabetic, cardiovascular events-free hemodialysis patients. Kidney Int 2005; 68: 1294-302.
Lee MH, Ko KM, Ahn SW, et al. The impact of kidney transplantation on 24-hour ambulatory blood pressure in end-stage renal disease patients. J Am Soc Hypertens 2015; 9: 427-34.
Mallamaci F, D’Arrigo G, Tripepi R, et al. Office, standardized and 24-h ambulatory blood pressure and renal function loss in renal transplant patients. J Hypertens 2018; 36(1): 119-25.
Rahman M, Hsu JY, Desai N, et al. CRIC Study Investigators. Central blood pressure and cardiovascular outcomes in chronic kidney disease. Clin J Am Soc Nephrol 2018; 13(4): 585-95.
Sood MM, Akbari A, Manuel DG, et al. Longitudinal blood pressure in late-stage chronic kidney disease and the risk of end-stage kidney disease or mortality (best blood pressure in chronic kidney disease study). Hypertension 2017; 70(6): 1210-8.
Navaneethan SD, Schold JD, Jolly SE, et al. Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease. Kidney Int 2017; 92(5): 1272-81.
Hermida RC, Ayala DE, Mojón A, Fernández JR. sleep-time ambulatory BP is an independent prognostic marker of CKD. J Am Soc Nephrol 2017; 28(9): 2802-11.
Kazancioglu R. Risk factors for chronic kidney disease: An update. Kidney Int Suppl 2013; 3(4): 368-71.
Devonald MAJ, Karet FE. Targeting the renin angiotensin system in patients with renal disease. J R Soc Med 2002; 95(8): 391-7.
Chiurchiu C, Remuzzi G, Ruggenenti P. Angiotensin converting enzyme inhibition and renal protection in nondiabetic patients: the data of the meta-analyses. J Am Soc Nephrol 2005; 16(Suppl. 1): S58-63.
Der Mesropian PJ, Shaikh G, Cordero Torres E, Bilal A, Mathew RO. Antihypertensive therapy in nondiabetic chronic kidney disease: A review and update. Am Soc Hypertens 2018; 12(3): 154-81.
Weir MR, Lakkis JI, Jaar B, et al. Use of renin-angiotensin system blockade in advanced CKD: An NKF-KDOQI controversies report. Am J Kidney Dis 2018; pii: S0272-6386(18): 30796-0.
Hsu TW, Liu JS, Hung SC, et al. Renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with advanced chronic kidney disease, hypertension, and anemia. JAMA Intern Med 2014; 174(3): 347-54.
Jovanovich AJ, Chonchol MB, Sobhi A, et al. Mineral metabolites, II inhibition and outcomes in advanced chronic kidney disease. Am J Nephrol 2015; 42(5): 361-8.
Oh YJ, Kim SM, Shin BC, et al. The impact of renin-angiotensin system blockade on renal outcomes and mortality in predialysis patients with advanced chronic kidney disease. PLoS One 2017; 12(1)e0170874
Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant 2016; 31(2): 255-61.
Ahmed AK, Kamath NS, El Kossi M, El Nahas AM. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant 2010; 25(12): 3977-82.
Onuigbo MA. Analytical review of the evidence for renoprotection by renin-angiotensin-aldosterone system blockade in chronic kidney disease - a call for caution. Nephron Clin Pract 2009; 113(2): c63-9.
Hamming I, van Goor H, Navis GJ. ACE inhibitor use and the increased long-term risk of renal failure in diabetes. [letter] Kidney Int 2006; 70(7): 1377-8. author reply 1378.
Ku E, McCulloch CE, Vittinghoff E, Lin F. Use of antihypertensive agents and association with risk of adverse outcomes in chronic kidney disease: focus on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. J Am Heart Assoc 2018; 7(19)e009992
Georgianos PI, Vaios V, Eleftheriadis T, Zebekakis P, Liakopoulos V. Mineralocorticoid antagonists in ESRD: An overview of clinical trial evidence. Curr Vasc Pharmacol 2017; 15(6): 599-606.
Agarwal R, Garza D, Mayo MR, et al. Patiromer to enable spironolactone use in the treatment of patients with resistant hypertension and chronic kidney disease: Rationale and design of the AMBER study. Am J Nephrol 2018; 48(3): 172-80.
Kopp UC. Role of renal sensory nerves in physiological and pathophysiological conditions. Am J Physiol Regul Comp Physiol 2015; 308: R79-95.
Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011; 57: 911-7.
Symplicity HTN-2 Investigators. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): A randomised controlled trial. Lancet 2010; 376: 1903-9.
Bhatt DL, Kandzari DE, O’Neill WW, et al. SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014; 370: 1393-401.
Townsend RR, Mahfoud F, Kandzari DE, et al. SPYRAL HTN-OFF MED trial investigators. Catheter- based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN- OFF MED): A randomised, sham-controlled, proof-of-concept trial. Lancet 2017; 390: 2160-70.
Kandzari DE, Böhm M, Mahfoud F, et al. SPYRAL HTN-ON MED Trial Investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN- ON MED proof- of-concept randomized trial. Lancet 2018; 391: 2346-55.
Azizi M, Schmieder RE, Mahfoud F, et al. RADIANCE-HTN Investigators. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE- HTN SOLO): A multicentre, international, single- blind, randomised, sham- controlled trial. Lancet 2018; 391: 2335-45.
Wyatt CM, Textor SC. Emerging evidence on renal denervation for the treatment of hypertension. Kidney Int 2018; 94(4): 644-6.
Aroor AR, Demarco VG, Jia G, et al. The role of tissue Renin - Angiotensin - aldosterone system in the development of endothelial dysfunction and arterial stiffness. Front Endocrinol 2013; 4: 161.
Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res 2014; 114: 1804-14.
Harrison DG. The immune system in hypertension. Trans Am Clin Climatol Assoc 2014; 125: 130-40.
Liakopoulos V, Georgianos PI, Eleftheriadis T, Sarafidis PA. Epigenetic mechanisms and kidney diseases. Curr Med Chem 2011; 18(12): 1733-9.
Trionfini P, Benigni A, Remuzzi G. MicroRNAs in kidney physiology and disease. Nat Rev Nephrol 2015; 11(1): 23.
Brandenburger T, Salgado Somoza A, Devaux Y, Lorenzen JM. Noncoding RNAs in acute kidney injury. Kidney Int 2018; 94(5): 870-81.
Zarjou A, Yang S, Abraham E, Agarwal A, Liu G. Identification of a microRNA signature in renal fibrosis: Role of miR-21. Am J Physiol Renal Physiol 2011; 301: F793-801.
Zhong X, Chung AC, Chen HY, Meng XM, Lan HY. Smad3- mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol 2011; 22: 1668-81.
Li X, Wei Y, Wang Z. microRNA-21 and hypertension. Hypertens Res 2018; 41(9): 649-61.
Parthenakis F, Marketou M, Kontaraki J, et al. Low levels of microRNA-21 are a marker of reduced arterial stiffness in well-controlled hypertension. J Clin Hypertens (Greenwich) 2017; 19: 235-40.
Marques FZ, Charchar FJ. MicroRNAs in essential hypertension and blood pressure regulation. Adv Exp Med Biol 2015; 888: 215-35.
Kemp JR, Unal H, Desnoyer R, Yue H, Bhatnagar A, Karnik SS. Angiotensin II-regulated microRNA 483-3p directly targets multiple components of the renin-angiotensin system. J Mol Cell Cardiol 2014; 75: 25-39.
Marques FZ, Campain AE, Tomaszewski M, et al. Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension 2011; 58: 1093-8.
Romero DG, Plonczynski MW, Carvajal CA, Gomez-Sanchez EP, Gomez-Sanchez CE. Microribonucleic acid-21 increases aldosterone secretion and proliferation in H295R human adrenocortical cells. Endocrinology 2008; 149: 2477-83.
Leimena C, Qiu H. Non-coding RNA in the pathogenesis, progression and treatment of hypertension. Int J Mol Sci 2018; 19(4): 927.
Zhao N, Koenig SN, Trask AJ, et al. Mir145 regulates TGFBR2 expression and matrix synthesis in vascular smooth muscle cells. Circ Res 2015; 116: 23-34.
Sun HX, Zeng DY, Li RT, et al. Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension 2012; 60: 1407-14.
Zhang J, Zhao F, Yu X, Lu X, Zheng G. MicroRNA- 155 modulates the proliferation of vascular smooth muscle cells by targeting endothelial nitric oxide synthase. Int J Mol Med 2015; 35: 1708-14.
O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007; 104: 1604-9.
Neal CS, Michael MZ, Pimlott LK, Yong TY, Li JY, Gleadle JM. Circulating microRNA expression is reduced in chronic kidney disease. Nephrol Dial Transplant 2011; 26: 3794-802.
Klimczak D, Kuch M, Pilecki T, Żochowska D, Wirkowska A, Pączek L. Plasma microRNA-155-5p is increased among patients with chronic kidney disease and nocturnal hypertension. J Am Soc Hypertens 2017; 11(12): 831-41.
Nandakumar P, Tin A, Grove ML, et al. MicroRNAs in the miR-17 and miR-15 families are downregulated in chronic kidney disease with hypertension. PLoS One 2017; 12e0176734
McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology 2014; 142: 24-31.
Yang T, Santisteban MM, Rodriguez V, et al. Gut dysbiosis is linked to hypertension. Hypertension 2015; 65: 1331-40.
Mell B, Jala VR, Mathew AV, et al. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 2015; 47: 187-97.
Li J, Zhao F, Wang Y, et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 2017; 5(1): 14.
Wilck N, Matus MG, Kearney SM, et al. Salt- responsive gut commensal modulates TH17 axis and disease. Nature 2017; 551: 585-9.
Vaziri ND, Wong J, Pahl M, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013; 83: 308-15.
Felizardo RJ, Castoldi A. Andrade- Oliveira V, Câmara NO. The microbiota and chronic kidney diseases: A double- edged sword. Clin Transl Immunology 2016; 5(6)e86
Ranganathan N, Friedman EA, Tam P, Rao V, Ranganathan P, Dheer R. Probiotic dietary supplementation in patients with stage 3 and 4 chronic kidney disease: A 6-month pilot scale trial in Canada. Curr Med Res Opin 2009; 25: 1919-30.
Fukuuchi F, Hida M, Aiba Y, et al. Intestinal bacteria- derived putrefactants in chronic renal failure. Clin Exp Nephrol 2002; 6: 99-104.
Vaziri ND. CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens 2012; 21(6): 587-92.
Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. Gut bacterial translocation is associated with microinflammation in end- stage renal disease patients. Nephrology 2012; 17: 733-8.
Kikuchi M, Ueno M, Itoh Y, Suda W, Hattori M. Uremic toxin- producing gut microbiota in rats with chronic kidney disease. Nephron 2017; 135: 51-60.
Xu KY, Xia GH, Lu JQ, et al. Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine- N-oxide in chronic kidney disease patients. Sci Rep 2017; 7: 1445.
Zoccali C, Tripepi G, Dounousi E, Mallamaci F. Chronic kidney disease (CKD) as a systemic disease: whole body autoregulation and inter-organcross-talk. Kidney Blood Press Res 2014; 39(2-3): 134-41.
Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol 2018; 14(7): 442-56.

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Year: 2020
Page: [45 - 54]
Pages: 10
DOI: 10.2174/1573402115666190415153554

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