E. HÜR, M. ERTİLAV, D. BOZKURT, B. ARDA, E. Y. SÖZMEN, S. ŞEN, A. BAŞCI, F. AKÇİÇEK, Ş. DUMAN

Antibiyotik tedavisine ek olarak oktreotid uygulanması deneysel peritonit modelinde ultrafiltrasyon yetmezliğini engelleyebilir

Amaç: Ultrafiltrasyon (UF) yetmezliği genellikle periton diyalizi (PD) peritonitine eşlik eder. Oktreotid (OCT) birçok hücrede anti-proliferatif etki gösterir. Bu çalışmayla peritonitlerde antibiyotik tedavisine ilaveten kullanılan OCT’nin etkinliğini araştırmayı amaçladık. Yöntem ve Gereç: Üremik-olmayan kırk dişi sıçan, “tedavisiz grup (Kontrol, n=12)”, “peritonit grup 1.5ml E.Coli (107CFU/ml)(E.Coli, n=12)”, “antibiyotik grubu (AB)(E.Coli+AB, sefazolin 50mg/kg n=8)” ve “OCT grup, E.Coli+AB+50μg/kg OCT periton içine (E.Coli+AB+OCT, n=8)” olmak üzere dört gruba ayrıldı. Altı saat sonra 3.86% glukoz içeren PD solüsyonu ile bir saatlik PET yapıldı. D1/D0 glukoz, UF volümü, diyalizat hücre sayımı, diyalizat proteini ve sitokinler ölçüldü. Tüm diyalizat örneklerden bakteriyolojik kültür yapıldı. Bulgular: E.Coli maruziyeti permeabilite artışı ile UF yetersizliğine yol açar. Antibiyotik tedavisi UF kapasitesini kısmen korur. Peritonite bağlı UF yetersizliği A.B+OCT tedavisi ile tümden engellenmiştir. Her iki tedavi, lokal TGF $\beta$ 1 üretimini inhibe ederek ve diyalizat hücre sayısını azaltarak UF yetmezliğini azaltmıştır. Sonuç: Diyalizata OCT eklenmesi peritonit nedeniyle tetiklenen UF yetersizliğini engellemeye yardım edebilir, akut dönemde sitokinlerin aşırı ekspresyonunu ve peritonit sırasındaki hücre infiltrasyonunu inhibe ederek periton canlılığını korur. Uzun vadede periton fibrozunu azaltabilir.

Octreotide in addition to antibiotic treatment may prevent ultrafiltration failure in experimental peritonitis model

Aim: Ultrafiltration (UF) failure is usually associated with peritoneal dialysis (PD) peritonitis. Octreotide (OCT) has antiproliferative effects on many cells. The present study aimed to investigate the effect of OCT on antibiotic treatment of peritonitis. Material and Methods: Forty non-uremic female rats, were divided into four groups receiving no treatment (Control, n=12); a peritonitis group which received 1.5ml suspension of E.Coli (107CFU/ml)(E.Coli, n=12); an antibiotic group which received 1.5ml suspension of E.Coli (107CFU/ml)+antibiotic (AB, cefazoline 50 mg/kg)(E.Coli+AB, n=8) and a OCT group which received E.Coli+AB+50μg/kg OCT intraperitoneally (E.Coli+AB+OCT, n=8). After six hours, a onehour PET was performed with 3.86% glucose PD solution; and D1/D0 glucose, UF volume, dialysate cell count, dialysate protein and cytokines were determined. A bacteriological culture was performed for all dialysates. Results: E.Coli exposure causes peritonitis with an increase in permeability leading to UF failure. Antibiotic treatment partially preserves UF capacity. Peritonitis induced UF failure which was completely prevented by AB plus OCT treatment. Both treatments led to attenuation of UF failure by inhibiting local TGF b-1 production and decreasing dialysate cell count. Conclusion: In conclusion, adding OCT in dialysate, may help to prevent peritonitis induced UF failure and preserve peritoneal viability by inhibiting acute cytokines over-expression and cell infiltration during peritonitis. In the long-term, it can decrease peritoneal fibrosis.

PDF

___

1. Bengt Rippe Peritoneal Dialysis: Principles, Techniques, and Adequacy . John Feehally , Jurgen Floege, Richard J. Johnson. Comprehensive Clinical Nephrology 3rd edition Phiedelphia Mosby Elsevier 2010:979-980
2. Krediet RT. The peritoneal membrane in chronic peritoneal dialysis. Kidney Int 55: 341-56, 1999
3. Tzamaloukas, AH. Inadequacy of dialysis and infectious complications of continuous ambulatory peritoneal dialysis (CAPD): Diagnosis, management and prevention. AKF Nephrol 8:29, 1991.
4. Mujais S, Nolph K, Gokal R et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis. Perit Dial Int. 2000;20 Suppl 4:S5-21. Review.
5. Pollock, CA, Ibels, LS, Hallett, MD. Loss of ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD). Perit Dial Int 9:107, 1989
6. Margetts, PJ, Churchill, DN. Acquired ultrafiltration dysfunction in peritoneal dialysis patients. J Am Soc Nephrol 13:2787, 2002.
7. Stegmayr, BG. Beta-blockers may cause ultrafiltration failure in peritoneal dialysis patients. Perit Dial Int 17:541, 1997.
8. Honda K, Nitta K, Horita S, et al. Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure. Nephron 72: 171-6, 1996.
9. Rubin J, Herrera GA, Collins D. An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 18: 97-102, 1991.
10. Fracasso A, Baggio B, Ossi E, et al. Glycosaminoglycans prevent the functional and morphological peritoneal derangement in an experimental model of peritoneal fibrosis. Am J Kidney Dis 33: 105-10, 1999
11. Honda K, Nitta K, Horita S, et al. Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration. Nephrol Dial Transplant 14: 1541-9, 1999
12. Falconi M, Vesentini S, Bassi C. Exocrine pancreatic response to SMS 2001-995. Ital J. Gastroenterol vol 23:3 p:156, 1991.
13. Fort E, Sauterau D, Silvain C, et al. A randomized trial of glypressin plus transdermal nitroglycerin versus octreotide in the control of acute variceal hemorrhage. Europ J Gastroenterol Hepatol vol 3 suppl 1 p:25, 1991.
14. Vinciguerra L, Contillo A, Bussci R, Parente A. Efficacy of octreotide+ 5 fluorouracil therapy in one patient with carcinoid syndrome. J Endoc Invest vol 13, suppl 1:235, 1990.
15. Brunani A, Crespi C, De Martin M, et al. Four year treatment with a long acting somatostatin analogue in a patient with Verner-Morrison syndrome. J Endoc Invest vol 14:685-9, 1991.
16. Annibale B, Corleto V, Gamboni G. Efficacy of somatostatin analog (SMS 201-995) on exocrine end endocrine gastric cells in Zollinger-Ellison syndrome (ZES) and antral G cell hyperfunction (AGHC). Europ J Gastroenterol Hepatol vol 3 suppl 1 p:34, 1991.
17. Amoric JC, Dreno B, Mourreaux P, Litoux P. Syndrome du glucagonoma. Interet de L’association dacarbazine-somatostatine. Sem Hop. Paris vol 67:1069-72, 1991.
18. Cello JP, Grendell JH, Basuk P Simon D, et al. Effect of octreotide on refractory AIDS-associated diarrhoea: a prospective, multicenter clinical trial. Ann Intern Med vol 115:705-10, 1991.
19. Duman S, Sen S, Duman C, Oreopoulos D.G. Effect Of Valsartan Versus Lisinopril On Peritoneal Sclerosis In Rats. Int J Artif Organs. 2005 Feb;28(2):156-63 .
20. Duman S, Sen S, Sözmen E.Y, Oreopoulos D.G. Atorvastatin Improves Peritoneal Sclerosis Induced By Hypertonic Pd Solution In Rats. Int J Artif Organs. 2005 Feb;28(2):170-6.
21. Duman S, Gunal AI, Sen S, et al. Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution? Perit Dial Int. 2001 Mar-Apr;21(2):219-24.
22. Duman S, Sen S, Duman C, et al. Improvement of peritoneal alterations induced by hipertonic PD solutions by ACE inhibitors and by AR blockers. Nephrol Dial Transplant 2003 vol 18,Suppl 4; s:474 (Abst).
23. Duman S, Sen S, Özkahya M, et al. Does Colchicine ameliorate peritoneal alterations induced by hypertonic pd solution? V. EUROPD European Peritoneal Dialysis Meeting, Brussel, Peritoneal Dialysis International vol 22:(1) s:113, 2002.
24. Duman S, Wieczorowska-Tobis K, Styszynski A, et al. Intraperitoneal enalapril ameliorates morphologic changes induced by hypertonic peritoneal dialysis solutions in rat peritoneum. Adv Perit Dial. 2004;20:31-6.
25. Gunal AI, Duman S, Sen S, et al. By reducing TGF beta 1, octreotide lessens the peritoneal derangements induced by a high glucose solution. J Nephrol May-Jun;14(3):184-9, 2001.
26. Gunal A, Celiker H, Akpolat N, et al. By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution. Perit Dial Int. May-Jun;22(3):301-6, 2002.
27. Van Manen JG, Korevaar JC, Dekker FW, et al. NECOSAD Study Group. Netherlands Cooperative Study on Adequacy of Dialysis. Changes in employment status in end-stage renal disease patients during their first year of dialysis. Perit Dial Int. 2001 Nov-Dec;21(6):595-601.
28. Bleyer AJ, Burkart JM, Russell GB, Adams PL. Dialysis modality and delayed graft function after cadaveric renal transplantation. J Am Soc Nephrol. 1999 Jan;10(1):154-9.
29. Duman S, Aşçi G, Töz H, et al. Patients with failed renal transplant may be suitable for peritoneal dialysis. Int Urol Nephrol. 2004;36(2):249-52.
30. Bosscha K, Nieuwenhuijs VB, Gooszen AW, et al. A standardised and reproducible model of intraabdominal infection and abscess formation in rats. Eur J Surg. 2000 Dec;166(12):963-7.
31. Zemel D, Krediet RT, Koomen GCM, et al. Interleukin-8 during peritonitis in patients treated with CAPD; an in vivo model of acute inflammation. Nephrol Dial Transplant 9: 169-174, 1994.
32. Tekstra J, Visser CE, Tuk CW, et al: Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients. J Am Soc Nephrol 7: 2379-2384, 1996.
33. Lai KN, Lai KB, Lam CW, et al: Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 35: 644-652, 2000.
34. Wang T, Cheng HH, Heimbürger O, et al: Effect of peritonitis on peritoneal transport characteristics: Glucose solution versus polyglucose solution. Kidney Int 57: 1704-1712, 2000.
35. Rodela H, Yuan ZY, Hay JB, et al: Reduced lymphatic drainage of dialysate from the peritoneal cavity during acute peritonitis in sheep. Perit Dial Int 16: 163-171, 1996.
36. Carlsson O, Rippe B: Peritoneal lymphatic absorption and solute exchange during zymosan-induced peritonitis in the rat. Am J Physiol 277: H1107-H1112, 1999.
37. Breborowicz A, Wieczorowska-Tobis K, Korybalska K, et al. The effect of a nitric oxide inhibitor (L-NAME) on peritoneal transport during dialysis in rats. Perit Dial Int 18: 188-192, 1998.
38. Zemel D, Koomen GCM, Hart AAM, et al. Relationship of TNF , interleukin-6 and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med 122: 686-696, 1993.
39. Davies M, Stylianou E, Yung S, et al. Proteoglycans of CAPD-dialysate fluid and mesothelium. Contr Nephrol 85: 134-141, 1990.
40. Lipkin GW, Forbes MA, Cooper EH, Turney JH: Hyaluronic acid metabolism and its clinical significance in patients treated by continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 8: 357-360, 1993.
41. Yung S, Coles GA, Williams JD, Davies M: The source and possible significance of hyaluronan in the peritoneal cavity. Kidney Int 46: 527-533, 1994.
42. Pannekeet MM, Zemel D, Koomen GCM, et al. Dialysate markers of peritoneal tissue during peritonitis and stable CAPD. Perit Dial Int 15: 217-225, 1995.
43. Yung S, Coles GA, Davies M: IL-1$beta$ , a major stimulator of hyaluronan synthesis in vivo of human peritoneal mesothelial cells: Relevance to peritonitis in CAPD. Kidney Int 50: 1337-1343, 1996.
44. Lai KN, Szeto CC, Lai KB, et al. Increased production of hyaluronan by peritoneal cells and its significance in patients on CAPD. Am J Kidney Dis 33: 318-324, 1999 .
45. Wang T, Cheng H, Heimburger O, et al. Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume. Kidney Int 53: 496-502, 1998.
46. Polubinska A, Pawlaczyk K, Kuzlan-Pawlaczyk M, et al: Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats. Kidney Int 57: 1182-1189, 2000.
47. Breborowicz A, Polubinska A, Moberly J, et al. Hyaluronan modifies inflammatory response and peritoneal permeability during peritonitis in rats. Am J Kidney Dis 37: 594-600, 2001.
48. Fussholler A, zur Nieden S, Grabensee B, Plum J: Peritoneal fluid and solute transport: influence of treatment time, peritoneal dialysis modality, and peritonitis incidence. J Am Soc Nephrol 13: 1055-1060, 2002.
49. Wong TY, Szeto CC, Lai KB, et al. Longitudinal study of peritoneal membrane function in continuous ambulatory peritoneal dialysis: Relationship with peritonitis and fibrosing factors. Perit Dial Int 20: 679-685, 2000.
50. Davies SJ, Bryan J, Phillips L, Russel GI: Longitudinal changes in peritoneal kinetics: The effects of peritoneal dialysis and peritonitis. Nephrol Dial Transplant 11: 498-506, 1996.
51. Selgas R, Fernandez-Reyes M-J, Bosque E, et al. Functional longevity of the human peritoneum: How long is continuous peritoneal dialysis possible? Results of a prospective medium long-term study. Am J Kidney Dis 23: 64-73, 1994.
52. Wang J, Zheng H, Hauer-Jensen M. Influence of Short-Term Octreotide Administration on Chronic Tissue Injury,Transforming Growth Factor beta (TGF-beta) Overexpression, and Collagen Accumulation in Irradiated Rat Intestine. J Pharmacol Exp Ther. 2001 Apr;297(1):35-42.
53. Chowers Y, Cahalon L, Lahav M, et al. Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha- and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells. J Immunol. 2000 Sep 15;165(6):2955-61.
54. Mishin I, Ghidirim G, Vozian M. Acute spontaneous chylous peritonitis: report of a case. J Gastrointestin Liver Dis. 2010 Sep;19(3):333-5.
55. Lee PH, Lin CL, Lai PC, Yang CW. Octreotide therapy for chylous ascites in a chronic dialysis patient. Nephrology (Carlton). 2005 Aug;10(4):344-7.