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Upper Gastrointestinal Disorders Among Dialysis Patients

Year 2019, Issue: 2, 135 - 141, 01.06.2019

Abstract

The prevalence of co-morbid gastrointestinal symptoms is high in dialysis patients, and dyspeptic symptoms, such as nausea, vomiting, and epigastric burning are the most common symptoms. Upper gastrointestinal disorders e.g., peptic ulcer disease and gastroparesis underlie most of these symptoms, while less common but severe complications are also likely that include gastrointestinal bleeding from gastric antral vascular ectasia, erosions or ulcers. Incidence of gastrointestinal disorders is considered to increase with the duration of renal failure, independent of dialysis modality. While uremia and dialysis have been linked to an increased risk of gastrointestinal tract lesions, pathogenesis of gastrointestinal dysfunction in end-stage renal disease is considered to be multifactorial and has not yet been clarified. In addition, conflicting data exist on the association of renal dysfunction with gastrointestinal disorders, and there are no explicit guidelines for the management of co-morbid gastrointestinal problems in patients with concomitant renal failure. Herein, we review the common upper gastrointestinal disorders that occur among dialysis patients, with an emphasis on prevalence, pathogenesis and diagnostic strategies

References

  • Nespor SL, Holley JL. Patients on hemodialysis rely on nephrologists and dialysis units for maintenance health care. ASAIO J 1992;38:M279-81.
  • Shirazian S, Radhakrishnan J. Gastrointestinal disorders and renal failure: exploring the connection. Nat Rev Nephrol 2010; 6: 480-92. [CrossRef]
  • Strid H, Simrén M, Johansson AC, Svedlund J, Samuelsson O, Björnsson ES. The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being. Nephrol Dial Transplant 2002;17:1434-9.
  • Abu Farsakh NA, Roweily E, Rababaa M, Butchoun R. Brief report: evaluation of the upper gastrointestinal tract in uraemic patients undergoing haemodialysis. Nephrol Dial Transplant 1996;11:847-50.
  • Chong VH, Tan J. Prevalence of gastrointestinal and psychosomatic symptoms among Asian patients undergoing regular hemodialysis. Nephrology (Carlton) 2013; 18: 97-103. [CrossRef]
  • Etemad B. Gastrointestinal complications of renal failure. Gastroenterol Clin North Am 1998; 27: 875-92.
  • Barri YM, Golper TA. Gastrointestinal disease in dialysis patients. 2016. Available at: http://www.uptodate.com/contents/gastrointestinal- disease-in-dialysis-patients. Accessed on: March 26, 2019
  • Riddell R, Jain D. Gastrointestinal Manifestations of Extraintestinal Disorders and Systemic Disease. Chapter 8. In: Lewin, Weinstein, and Riddell’s Gastrointestinal Pathology and Its Clinical Implications. Wloters Kluwer; UK, 2014, pp. 390-3. Available at: http://www. lww.co.uk/media/Riddell-Ch8-Gastrointestinal-Manifestations-of- Extraintestinal-Disorders-and-Systematic-Disease.pdf
  • Kalman RS, Pedrosa MC. Evidence-based review of gastrointestinal bleeding in the chronic kidney disease patient. Semin Dial 2015;28:68-74. [CrossRef]
  • Thomas R, Panackal C, John M, et al. Gastrointestinal complications in patients with chronic kidney disease. A 5-year retrospective study from a tertiary referral center. Ren Fail 2013; 35: 49-55. [CrossRef]
  • Muto S, Murayama N, Asano Y, Hosoda S, Miyata M. Hypergastrinemia and achlorhydria in chronic renal failure. Nephron 1985; 40: 143-8. [CrossRef]
  • Laaksonen S, Voipio-Pulkki L, Erkinjuntti M, Asola M, Falck B. Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia? J Intern Med 2000; 248: 21-6.
  • Lee YC, Hung SY, Wang HH, Wang HK, Lin CW, Chang MY et al. Different Risk of Common Gastrointestinal Disease Between Groups Undergoing Hemodialysis or Peritoneal Dialysis or With Non-End Stage Renal Disease: A Nationwide Population-Based Cohort Study. Medicine (Baltimore) 2015; 94: e1482. [CrossRef]
  • Hammer J, Oesterreicher C, Hammer K, Koch U, Traindl O, Kovarik J. Chronic gastrointestinal symptoms in hemodialysis patients. Wien Klin Wochenschr 1998; 110:287-91.
  • Santos PR, Monteiro DL, de Paula PH, et al. Volaemic status and dyspepsia in end-stage renal disease patients. Nephrology (Carlton) 2015; 20: 519-22. [CrossRef]
  • Khedmat H, Ahmadzad-Asl M, Amini M, et al. Gastro-duodenal lesions and Helicobacter pylori infection in uremic patients and renal transplant recipients. Transplant Proc 2007; 39: 1003-7. [CrossRef]
  • Kang JY, Ho KY, Yeoh KG, et al. Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection. J Gastroenterol Hepatol 1999; 14: 771-8.
  • Nardone G, Rocco A, Fiorillo M, et al. Gastroduodenal lesions and Helicobacter pylori infection in dyspeptic patients with and without chronic renal failure. Helicobacter 2005; 10: 53-8. [CrossRef]
  • Stolic RV, Jovanovic AN, Zivic ZP, et al. Influence of the level of renal insufficiency on endoscopic changes in the upper gastrointestinal tract. Am J Med Sci 2008; 336: 39-43. [CrossRef]
  • Bacci MR, Chehter EZ. Dyspepsia among patients with chronic kidney disease: a cross sectional study. Int Arch Med 2013; 6: 43. [CrossRef]
  • Sugimoto M, Sakai K, Kita M, Imanishi J, Yamaoka Y. Prevalence of Helicobacter pylori infection in long-term hemodialysis patients. Kidney Int 2009; 75: 96-103. [CrossRef]
  • Luzza F, Imeneo M, Maletta M, et al. Helicobacter pylori-specific IgG in chronic haemodialysis patients: relationship of hypergastrinaemia to positive serology. Nephrol Dial Transplant 1996; 11: 120-4.
  • Huang JJ, Huang CJ, Ruaan MK, Chen KW, Yen TS, Sheu BS. Diagnostic efficacy of (13)C-urea breath test for Helicobacter pylori infection in hemodialysis patients. Am J Kidney Dis 2000; 36: 124-9. [CrossRef]
  • Wang YL, Sheu BS, Huang JJ, Yang HB. Noninvasive stool antigen assay can effectively screen Helicobacter pylori Infection and assess success of eradication therapy in hemodialysis patients. Am J Kidney Dis 2001; 38: 98-103. [CrossRef]
  • Talley NJ, American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology 2005; 129: 1753-5. [CrossRef]
  • Sheu BS, Huang JJ. Helicobacter pylori infection in hemodialysis patients. Int J Artif Organs 2001; 24: 669-70.
  • Chang SS, Hu HY. Lower Helicobacter pylori infection rate in chronic kidney disease and end-stage renal disease patients with peptic ulcer disease. J Chin Med Assoc 2014; 77: 354-9. [CrossRef]
  • Nakajima F, Sakaguchi M, Amemoto K, et al. Helicobacter pylori in patients receiving long-term dialysis. Am J Nephrol 2002; 22: 468-72. [CrossRef]
  • Cocchiara G, Romano M, Buscemi G, Maione C, Maniaci S, Romano G. Advantage of eradication therapy for Helicobacter pylori before kidney transplantation in uremic patients. Transplant Proc 2007; 39: 3041-3. [CrossRef]
  • Sugimoto M, Yamaoka Y. Review of Helicobacter pylori infection and chronic renal failure. Ther Apher Dial 2011; 15: 1-9. [CrossRef]
  • Schoonjans R, Van VB, Vandamme W, et al. Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori. Clin Nephrol 2002; 57: 201-7.
  • Sohal AS, Gangji AS, Crowther MA, Treleaven D. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006;118: 417- 22. [CrossRef]
  • Wasse H, Gillen DL, Ball AM, et al. Risk factors for upper gastrointestinal bleeding among end-stage renal disease patients. Kidney Int 2003;64: 1455-61. [CrossRef]
  • Ikeda N, Inoue T, Kobayashi K, Watanabe Y, Suzuki H. Emergency gastrointestinal bleeding in dialysis patients five years’ experience in a single dialysis center. Urol Nephrol Open Access J 2015; 2: 00021. [CrossRef]
  • Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut 1996; 38: 316-21.
  • Akmal M, Sawelson S, Karubian F, Gadallah M. The prevalence and significance of occult blood loss in patients with predialysis advanced chronic renal failure (CRF), or receiving dialytic therapy. Clin Nephrol 1994; 42: 198-202.
  • Chalasani N, Cotsonis G, Wilcox CM. Upper gastrointestinal bleeding in patients with chronic renal failure: role of vascular ectasia. Am J Gastroenterol 1996; 91: 2329-32.
  • Poralla T. Angiodysplasia in the renal patient: how to diagnose and how to treat? Nephrol Dial Transplant 1998; 13: 2188-91.
  • Alvarez L, Puleo J, Balint JA. Investigation of gastrointestinal bleeding in patients with end stage renal disease. Am J Gastroenterol 1993;88:30-3.
  • Zuckerman GR, Cornette GL, Clouse RE, Harter HR. Upper gastrointestinal bleeding in patients with chronic renal failure. Ann Intern Med 1985; 102: 588-92.
  • Cheung J, Yu A, LaBossiere J, Zhu Q, Fedorak RN. Peptic ulcer bleeding outcomes adversely affected by end-stage renal disease. Gastrointest Endosc 2010; 71: 44-9. [CrossRef]
  • Freeman JG, Cobden I, Heaton A, Keir M. Gastric emptying in chronic renal failure. Br Med J (Clin Res Ed) 1985; 291:1048.
  • McNamee PT, Moore GW, McGeown MG, Doherty CC, Collins BJ. Gastric emptying in chronic renal failure. Br Med J (Clin Res Ed) 1985;291:310-1.
  • Soffer EE, Geva B, Helman C, Avni Y, Bar-Meir. Gastric emptying in chronic renal failure patients on hemodialysis. J Clin Gastroenterol 1987; 9: 651-3.
  • Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 1993; 38: 1569-80.
  • Van Vlem B, Schoonjans R, Vanholder R, et al. Delayed gastric emptying in dyspeptic chronic hemodialysis patients. Am J Kidney Dis 2000; 36: 962-8.
  • Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med 2001; 161: 1989-96.
  • Strid H, Simrén M, Stotzer PO, Abrahamsson H, Björnsson ES. Delay in gastric emptying in patients with chronic renal failure. Scand J Gastroenterol 2004; 39: 516-20.
  • Brown-Cartwright D, Smith HJ, Feldman M. Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Gastroenterology 1988;95:49-51.
  • Bird NJ, Streather CP, O’Doherty MJ, Barton IK, Gaunt JI, Nunan TO. Gastric emptying in patients with chronic renal failure on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 1994;9:287-90.

DIYALIZ HASTALARINDA ÜST GASTROINTESTINAL SISTEM HASTALIKLARI

Year 2019, Issue: 2, 135 - 141, 01.06.2019

Abstract

Diyaliz hastalarında komorbid gastrointestinal semptomlar yüksek prevalansa sahiptir. Bulantı, kusma ve mide yanması gibi dispeptik semptomlar en yaygın gastrointestinal semptomlardır. Üst gastrointestinal sistem hastalıkları örn., peptic ülser hastalığı ve gastroparezi bu semptomların önemli nedenleri arasındadır. Ek olarak gastrik antral vasküler ektaziye bağlı kanama erozyon veya ülser gelişimi gibi nadir ancak şiddetli komplikasyonlar da gözlenebilmektedir. Gastrointestinal hastalık insidansının, diyaliz türünden bağımsız ve renal yetmezlik süresi ile orantılı olarak artış gösterdiği kabul edilmektedir. Üremi ve diyaliz gastrointestinal sistem lezyon gelişimi için bir risk faktörü olmakla birlikte, son dönem renal hastalığa bağlı gastrointestinal fonksiyon bozukluğu gelişimi çok faktörlü ve henüz netlik kazanmamış bir patogeneze sahiptir. Ek olarak, renal fonksiyon bozukluğu ve gastrointestinal bozukluklar arasındaki ilişkiye dair çelişkili veriler mevcut olup, renal yetmezlik zemininde gelişen gastrointestinal hastalıkların yönetimine dair özgül kılavuzlar bulunmamaktadır. Bu derleme makalede, diyaliz hastalarında sık gözlenen üst gastrointestinal sistem hastalıkları prevalans, patogenez ve tanısal yaklaşımlar bazında sunulmaktadır

References

  • Nespor SL, Holley JL. Patients on hemodialysis rely on nephrologists and dialysis units for maintenance health care. ASAIO J 1992;38:M279-81.
  • Shirazian S, Radhakrishnan J. Gastrointestinal disorders and renal failure: exploring the connection. Nat Rev Nephrol 2010; 6: 480-92. [CrossRef]
  • Strid H, Simrén M, Johansson AC, Svedlund J, Samuelsson O, Björnsson ES. The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being. Nephrol Dial Transplant 2002;17:1434-9.
  • Abu Farsakh NA, Roweily E, Rababaa M, Butchoun R. Brief report: evaluation of the upper gastrointestinal tract in uraemic patients undergoing haemodialysis. Nephrol Dial Transplant 1996;11:847-50.
  • Chong VH, Tan J. Prevalence of gastrointestinal and psychosomatic symptoms among Asian patients undergoing regular hemodialysis. Nephrology (Carlton) 2013; 18: 97-103. [CrossRef]
  • Etemad B. Gastrointestinal complications of renal failure. Gastroenterol Clin North Am 1998; 27: 875-92.
  • Barri YM, Golper TA. Gastrointestinal disease in dialysis patients. 2016. Available at: http://www.uptodate.com/contents/gastrointestinal- disease-in-dialysis-patients. Accessed on: March 26, 2019
  • Riddell R, Jain D. Gastrointestinal Manifestations of Extraintestinal Disorders and Systemic Disease. Chapter 8. In: Lewin, Weinstein, and Riddell’s Gastrointestinal Pathology and Its Clinical Implications. Wloters Kluwer; UK, 2014, pp. 390-3. Available at: http://www. lww.co.uk/media/Riddell-Ch8-Gastrointestinal-Manifestations-of- Extraintestinal-Disorders-and-Systematic-Disease.pdf
  • Kalman RS, Pedrosa MC. Evidence-based review of gastrointestinal bleeding in the chronic kidney disease patient. Semin Dial 2015;28:68-74. [CrossRef]
  • Thomas R, Panackal C, John M, et al. Gastrointestinal complications in patients with chronic kidney disease. A 5-year retrospective study from a tertiary referral center. Ren Fail 2013; 35: 49-55. [CrossRef]
  • Muto S, Murayama N, Asano Y, Hosoda S, Miyata M. Hypergastrinemia and achlorhydria in chronic renal failure. Nephron 1985; 40: 143-8. [CrossRef]
  • Laaksonen S, Voipio-Pulkki L, Erkinjuntti M, Asola M, Falck B. Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia? J Intern Med 2000; 248: 21-6.
  • Lee YC, Hung SY, Wang HH, Wang HK, Lin CW, Chang MY et al. Different Risk of Common Gastrointestinal Disease Between Groups Undergoing Hemodialysis or Peritoneal Dialysis or With Non-End Stage Renal Disease: A Nationwide Population-Based Cohort Study. Medicine (Baltimore) 2015; 94: e1482. [CrossRef]
  • Hammer J, Oesterreicher C, Hammer K, Koch U, Traindl O, Kovarik J. Chronic gastrointestinal symptoms in hemodialysis patients. Wien Klin Wochenschr 1998; 110:287-91.
  • Santos PR, Monteiro DL, de Paula PH, et al. Volaemic status and dyspepsia in end-stage renal disease patients. Nephrology (Carlton) 2015; 20: 519-22. [CrossRef]
  • Khedmat H, Ahmadzad-Asl M, Amini M, et al. Gastro-duodenal lesions and Helicobacter pylori infection in uremic patients and renal transplant recipients. Transplant Proc 2007; 39: 1003-7. [CrossRef]
  • Kang JY, Ho KY, Yeoh KG, et al. Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection. J Gastroenterol Hepatol 1999; 14: 771-8.
  • Nardone G, Rocco A, Fiorillo M, et al. Gastroduodenal lesions and Helicobacter pylori infection in dyspeptic patients with and without chronic renal failure. Helicobacter 2005; 10: 53-8. [CrossRef]
  • Stolic RV, Jovanovic AN, Zivic ZP, et al. Influence of the level of renal insufficiency on endoscopic changes in the upper gastrointestinal tract. Am J Med Sci 2008; 336: 39-43. [CrossRef]
  • Bacci MR, Chehter EZ. Dyspepsia among patients with chronic kidney disease: a cross sectional study. Int Arch Med 2013; 6: 43. [CrossRef]
  • Sugimoto M, Sakai K, Kita M, Imanishi J, Yamaoka Y. Prevalence of Helicobacter pylori infection in long-term hemodialysis patients. Kidney Int 2009; 75: 96-103. [CrossRef]
  • Luzza F, Imeneo M, Maletta M, et al. Helicobacter pylori-specific IgG in chronic haemodialysis patients: relationship of hypergastrinaemia to positive serology. Nephrol Dial Transplant 1996; 11: 120-4.
  • Huang JJ, Huang CJ, Ruaan MK, Chen KW, Yen TS, Sheu BS. Diagnostic efficacy of (13)C-urea breath test for Helicobacter pylori infection in hemodialysis patients. Am J Kidney Dis 2000; 36: 124-9. [CrossRef]
  • Wang YL, Sheu BS, Huang JJ, Yang HB. Noninvasive stool antigen assay can effectively screen Helicobacter pylori Infection and assess success of eradication therapy in hemodialysis patients. Am J Kidney Dis 2001; 38: 98-103. [CrossRef]
  • Talley NJ, American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology 2005; 129: 1753-5. [CrossRef]
  • Sheu BS, Huang JJ. Helicobacter pylori infection in hemodialysis patients. Int J Artif Organs 2001; 24: 669-70.
  • Chang SS, Hu HY. Lower Helicobacter pylori infection rate in chronic kidney disease and end-stage renal disease patients with peptic ulcer disease. J Chin Med Assoc 2014; 77: 354-9. [CrossRef]
  • Nakajima F, Sakaguchi M, Amemoto K, et al. Helicobacter pylori in patients receiving long-term dialysis. Am J Nephrol 2002; 22: 468-72. [CrossRef]
  • Cocchiara G, Romano M, Buscemi G, Maione C, Maniaci S, Romano G. Advantage of eradication therapy for Helicobacter pylori before kidney transplantation in uremic patients. Transplant Proc 2007; 39: 3041-3. [CrossRef]
  • Sugimoto M, Yamaoka Y. Review of Helicobacter pylori infection and chronic renal failure. Ther Apher Dial 2011; 15: 1-9. [CrossRef]
  • Schoonjans R, Van VB, Vandamme W, et al. Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori. Clin Nephrol 2002; 57: 201-7.
  • Sohal AS, Gangji AS, Crowther MA, Treleaven D. Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006;118: 417- 22. [CrossRef]
  • Wasse H, Gillen DL, Ball AM, et al. Risk factors for upper gastrointestinal bleeding among end-stage renal disease patients. Kidney Int 2003;64: 1455-61. [CrossRef]
  • Ikeda N, Inoue T, Kobayashi K, Watanabe Y, Suzuki H. Emergency gastrointestinal bleeding in dialysis patients five years’ experience in a single dialysis center. Urol Nephrol Open Access J 2015; 2: 00021. [CrossRef]
  • Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut 1996; 38: 316-21.
  • Akmal M, Sawelson S, Karubian F, Gadallah M. The prevalence and significance of occult blood loss in patients with predialysis advanced chronic renal failure (CRF), or receiving dialytic therapy. Clin Nephrol 1994; 42: 198-202.
  • Chalasani N, Cotsonis G, Wilcox CM. Upper gastrointestinal bleeding in patients with chronic renal failure: role of vascular ectasia. Am J Gastroenterol 1996; 91: 2329-32.
  • Poralla T. Angiodysplasia in the renal patient: how to diagnose and how to treat? Nephrol Dial Transplant 1998; 13: 2188-91.
  • Alvarez L, Puleo J, Balint JA. Investigation of gastrointestinal bleeding in patients with end stage renal disease. Am J Gastroenterol 1993;88:30-3.
  • Zuckerman GR, Cornette GL, Clouse RE, Harter HR. Upper gastrointestinal bleeding in patients with chronic renal failure. Ann Intern Med 1985; 102: 588-92.
  • Cheung J, Yu A, LaBossiere J, Zhu Q, Fedorak RN. Peptic ulcer bleeding outcomes adversely affected by end-stage renal disease. Gastrointest Endosc 2010; 71: 44-9. [CrossRef]
  • Freeman JG, Cobden I, Heaton A, Keir M. Gastric emptying in chronic renal failure. Br Med J (Clin Res Ed) 1985; 291:1048.
  • McNamee PT, Moore GW, McGeown MG, Doherty CC, Collins BJ. Gastric emptying in chronic renal failure. Br Med J (Clin Res Ed) 1985;291:310-1.
  • Soffer EE, Geva B, Helman C, Avni Y, Bar-Meir. Gastric emptying in chronic renal failure patients on hemodialysis. J Clin Gastroenterol 1987; 9: 651-3.
  • Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci 1993; 38: 1569-80.
  • Van Vlem B, Schoonjans R, Vanholder R, et al. Delayed gastric emptying in dyspeptic chronic hemodialysis patients. Am J Kidney Dis 2000; 36: 962-8.
  • Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med 2001; 161: 1989-96.
  • Strid H, Simrén M, Stotzer PO, Abrahamsson H, Björnsson ES. Delay in gastric emptying in patients with chronic renal failure. Scand J Gastroenterol 2004; 39: 516-20.
  • Brown-Cartwright D, Smith HJ, Feldman M. Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Gastroenterology 1988;95:49-51.
  • Bird NJ, Streather CP, O’Doherty MJ, Barton IK, Gaunt JI, Nunan TO. Gastric emptying in patients with chronic renal failure on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 1994;9:287-90.
There are 50 citations in total.

Details

Primary Language English
Journal Section Collection
Authors

Şafak Kızıltaş

Sevgi Şahin

Publication Date June 1, 2019
Published in Issue Year 2019Issue: 2

Cite

EndNote Kızıltaş Ş, Şahin S (June 1, 2019) Upper Gastrointestinal Disorders Among Dialysis Patients. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 2 135–141.