Fibrosis peritoneal
Resumen
La diálisis peritoneal (DP) es una de las formas de sustitución de la función renal y como tratamiento abarca a más de 100.000 pacientes con insuficiencia renal crónica estadio V en todo el mundo, por lo que la tasa de prevalencia abarca entre el 10 y el 15% de la población en diálisis. Los mayores obstáculos para el tratamiento a largo plazo de la terapia son las infecciones y las alteraciones que sufre la membrana peritoneal al exponerse a las soluciones dialíticas, que generan pérdida de la capacidad dialítica, con modificaciones en la difusión como en la ultrafiltración. Estas alteraciones pueden afectar a casi el 50% de los pacientes en diálisis peritoneal. Incluyen fibrosis progresiva, angiogénesis y degeneración vascular. En un pequeño porcentaje la fibrosis ocurre en el peritoneo visceral conduciendo a su peor representación: esclerosis peritoneal encapsulante, con una alta tasa de mortalidad. Conocer la fisiopatología de dichas alteraciones, genera cambios en el uso de la terapia para evitar la aparición y progresión a la fibrosis, y de esa manera disminuir el “drop-out” de la técnica por agotamiento peritoneal. En este artículo se revisará algunos de los mecanismos de producción y las posibles medidas a tomar para disminuir la aparición de fibrosis peritoneal.
Citas
Di Paolo N, Sacchi G. Atlas of peritoneal histology. Perit Dial Int. 2000;20 Suppl 3:S5-96.
Li FK, Davenport A, Robson RL, Loetscher P, Rothlein R, Williams JD, et al. Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression. Kidney Int. 1998;54(6):2170-83.
Gandhi VC, Humayun HM, Ing TS, Daugirdas JT, Jablokow VR, Iwatsuki S, et al. Sclerotic thickening of the peritoneal membrane in maintenance peritoneal dialysis patients. Arch Intern Med. 1980;140:1201-03.
Williams JD, Craig KJ, Topley N, Von Ruhland C, Fallon M, Newman GR, et al. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol 2002;13:470-9.
Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemi cal basis of diabetic complications. N Engl J Med 1988; 318:1315-21.
Nakamura S, Tachikawa T, Tobita K, Miyazaki S, Sakai S, Morita T, et al. Role of advanced glycation end products and growth factors in peritoneal dysfunction in CAPD patients. Am J Kidney Dis. 2003;41(Suppl 1):S61-7.
Welten AG, Schalkwijk CG, ter Wee PM, Meijer S, van den Born J, Beelen RJ. Single exposure of mesothelial cells to glucose degradation products (GDPs) yields early advanced glycation end-products (AGEs) and a proinflammatory response. Perit Dial Int. 2003;23:213-21.
Inagi R, Miyata T, Yamamoto T, Suzuki D, Urakami K, Saito A, et al. Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis. FEBS Lett. 1999;463:260-4.
Witowski J, Wisniewska J, Korybalska K, Bender TO, Breborowicz A, Gahl GM, et al. Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells. J Am Soc Nephrol. 2001;12:2434-41.
Jörres A. Effect of peritoneal dialysis on peritoneal cell biology: peritoneal fibroblasts. Perit Dial Int. 1999;19(Suppl 2):S348-52.
Witowski J, Korybalska K, Wisniewska J, Breborowicz A, Gahl GM, Frei U, et al. Effect of glucose degradation products on human peritoneal mesothelial cell function. J Am Soc Nephrol. 2000; 11:729-39.
Morgan LW, Wieslander A, Davies M, Horiuchi T, Ohta Y, Beavis MJ, et al. Glucose degradation products (GDP) retard remesothelialization independently of Dglucose concentration. Kidney Int. 2003;64:1854-66.
Yanez-Mo M, Lara-Pezzi E, Selgas R, Ramirez-Huesca M, Domínguez-Jiménez C, Jiménez-Heffernan JA, et al. Peritoneal dialysis and epithelial-tomesenchymal transition of mesothelial cells. N Engl J Med. 2003;348:403-13. [Erratum in: N Engl J Med. 2005;353:2827].
Ito T, Yorioka N, Yamamoto M, Kataoka K, Yamakido M. Effect of glucose on intercellular junctions of cultured human peritoneal mesothelial cells. J Am Soc Nephrol. 2000;11:1969-79.
Leung JC, Chan LY, Li FF, Tang SC, Chan KW, Chan TM, et al. Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF. Nephrol Dial Transplant. 2005;20:1336-49.
Lai KN, Lai KB, Chan TM, Lam CW, Li FK, Leung JCK. Changes of cytokine profile during peritonitis in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 2000;35:644-52.
Bos HJ, van Bronswijk H, Helmerhorst TJ, Oe PL, Hoefsmit EC, Beelen RH. Distinct subpopulations of elicited human macrophages in peritoneal dialysis patients and women undergoing laparoscopy: a study on peroxidatic activity. J Leukocyte Biol.1988;43:172-8.
Shostak A, Pivnik E, Gotloib L. Cultured rat mesothelial cells generate hydrogen peroxide: a new player in peritoneal defense? J Am Soc Nephrol. 1996;7:2371-8.
Jörres A, Topley N, Steenweg L, Muller C, Kottgen E, Gahl GM. Inhibition of cytokine synthesis by peritoneal dialysate persists throughout the CAPD cycle. Am J Nephrol. 1992;12:80-5.
Ha H, Cha MK, Choi HN, Lee HB. Effects of peritoneal dialysis solutions on the secretion of growth factors and extracellular matrix proteins by human peritoneal mesothelial cells. Perit Dial Int. 2002;22:171-7.
Jones S, Holmes C, Krediet RT, Mackenzie RK, Faict D, Tranæus A, et al. Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels. Kidney Int. 2001;59:1529-38.
Mandl–Weber S, Cohen CD, Haslinger B, Kretzler M, Sitter T. Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cells. Kidney Int. 2002;61:570-8.
Dobbie JW, Anderson JD, Hind C. Long-term effects of peritoneal dialysis on peritoneal morphology. Perit Dial Int. 1994;14(Suppl 3):S16-20.
Flessner MF. The effect of fibrosis on peritoneal transport. Contrib Nephrol. 2006;150:174-80.
Lai KN, Leung JC, Chan LY, Li FF, Tang SC, Lam MF, et al. Differential expression of receptors for advanced glycation end-products in peritoneal mesothelial cells exposed to glucose degradation products. Clin Exp Immunol. 2004;138:466-75.
Ito H, Hamada C, Ro Y, Ito Y, Hirahara I, Tomino Y. Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models. Kidney Int. 2004;65:1927-36.
Nakayama M, Kawaguchi Y, Yamada K, Hasegawa T, Takazoe K, Katoh N, et al. Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD. Kidney Int. 1997;51:182-6.
Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kB. Diabetes 2001;50:2792-808.
Ogata S, Yorioka N, Nishida Y, Shao JC, Yamakida M. Expression of receptor for advanced glycation end product mRNA by human peritoneal mesothelial cells. Nephron 2000;86:245-6.
Schwenger V, Morath C, Salava A, Amann K, Seregin Y, Deppisch R, et al. Damage to the peritoneal membrane by glucose degradation products is mediated by the receptor for advanced glycation end-products. J Am Soc Nephrol. 2006;17:199-207.
De Vriese AS, Flyvbjerg A, Mortier S, Tilton RG, Lameire NH. Inhibition of the interaction of AGE–RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane. J Am Soc Nephrol. 2003;14:2109-18.
De Vriese AS, Tilton RG, Mortier S, Lameire NH. Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia. Nephrol Dial Transplant. 2006;21:2549-55.
Oldfield MD, Bach LA, Forbes JM, Nikolic–Paterson D, McRobert A, Thallas V, et al. Advanced glycation end products cause epithelial–myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest 2001; 108:1853–63.
Friedman JM. Obesity in the new millennium. Nature 2000;404:632-4.
Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res. 2004;59:287-304.
Nordfors L, Heimbürger O, Lonnqvist F, Lindholm B, Helmrich J, Schalling M, et al. Fat tissue accumulation during peritoneal dialysis is associated with a polymorphism in uncoupling protein 2. Kidney Int. 2000;57:1713-19.
Friedman AN. Adiposity in dialysis: good or bad? Semin Dial. 2006;19:136-40.
Beddhu S, Pappas LM, Ramkumar N, Samore M. Effects of body size and body composition on survival in hemodialysis patients. J Am Soc Nephrol.
;14:2366-72.
Araujo IC, Kamimura MA, Draibe S, Canziani ME, Manfredi SR, Avesani CM, et al. Nutritional parameters and mortality in incident hemodialysis patients. J Ren Nutr. 2006;16:27-35.
Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004;145:2273-82.
Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-a, in vivo. J Clin Endocrinol Metab. 1997;82:4196-200.
Axelsson J, Rashid Qureshi A, Suliman ME, Honda H, Pecoits-Filho R, Heimbürger O, et al. Truncal fat mass as a contributor to inflammation in end-stage renal failure. Am J Clin Nutr. 2004;80:1222-9.
Leung JC, Chan LY, Tang SC, Chu KM, Lai KN. Leptin induces TGF-b synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell. Kidney Int. 2006;69:2078-86.
- Loureiro J, Sandoval P, del Peso G, González-Mateo G, Fernández-Millara V, et al. (2013) Tamoxifen Ameliorates Peritoneal Membrane Damage byBlocking Mesothelial to Mesenchymal Transition in Peritoneal Dialysis. PLoS ONE 8(4):e61165.
Katsanos GS, Anogeianaki A, Orso C, Tetè S, Salini V, Antinolfi PL, et al. Mast cells and chemokines. J Biol Regul Homeost Agents. 2008;22:145-51.
Schilte MN, Celie JW, Wee PM, Beelen RH, van den Born J. Factors contributing to peritoneal tissue remodeling in peritoneal dialysis. Perit Dial Int. 2009;29:605-17.
Zareie M, Fabbrini P, Hekking LH, Keuning ED, Ter Wee PM, Beelen RH, et al. Novel role for mast cells in omental tissue remodeling and cell recruitment in experimental peritoneal dialysis. J Am Soc Nephrol. 2006;17:3447-57.
Alscher DM, Braun N, Biegger D, Fritz P. Peritoneal mast cells in peritoneal dialysis patients, particularly in encapsulating peritoneal sclerosis patients. Am J Kidney Dis. 2007;49:452-61.
Kawai T, Masaki T, Doi S, Arakawa T, Yokoyama Y, Doi T, et al. PPAR-γ agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-γ. Lab Invest. 2009;89:47-58.
Toblli JE, Ferrini MG, Cao G, Vernet D, Angerosa M, Gonzalez–Cadavid NF. Antifibrotic effects of pioglitazone on the kidney in a rat model of type 2 diabetes mellitus. Nephrol Dial Transplant. 2009;24:2384-91.
Sandoval P, Loureiro J, González-Mateo G, Pérez-Lozano ML, Maldonado-Rodríguez A, Sánchez-Tomero JA, et al. PPAR-γ agonist rosiglitazone protects peritoneal membrane from dialysis fluid–induced damage. Lab Invest. 2010;90:1517-32.
Li Y, Xie QH, You HZ, Tian J, Hao CM, Lin SY, et al. Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients-a randomized crossover trial. Perit Dial Int. 2012;32:507-15.
Rizos CV, Elisaf MS, Mikhailidis DP, Liberopoulos EN. How safe is the use of thiazolidinediones in clinical practice? Expert Opin Drug Saf. 2009;8:15-32.
Kihm LP, Müller-Krebs S, Klein J, Ehrlich G, Mertes L, Gross ML, et al. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J Am Soc Nephrol. 2011;22:914-26.
Lee EA, Oh JH, Lee HA, Kim SI, Park EW, Park KB, et al. Structural and functional alterations of the peritoneum after prolonged exposure to dialysis solutions: role of aminoguanidine. Perit Dial Int. 2001;21:245-53.
Zareie M, Tangelder GJ, ter Wee PM, Hekking LH, van Lambalgen AA, Keuning ED, et al. Beneficial effects of aminoguanidine on peritoneal microcirculation and tissue remodelling in a rat model of PD. Nephrol Dial Transplant.2005; 20:2783-92.
Miyoshi H, Taguchi T, Sugiura M, Takeuchi M, Yanagisawa K, Watanabe Y, et al. Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice. Horm Metab Res. 2002;34:371-7.
Kakuta T, Tanaka R, Satoh Y, Izuhara Y, Inagi R, Nangaku M, et al. Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats. Kidney Int. 2005;68:1326-36.
Duman S, Günal AI, Sen S, Asçi G, Ozkahya M, Terzioglu E, et al. Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution? Perit Dial Int. 2001;21:219-24.
Wolf G, Neilson EG. Angiotensin II as a renal growth factor. J Am Soc Nephrol. 1993;3:1531-40.
Fern RJ, Yesko CM, Thornhill BA, Kim HS, Smithies O, Chevalier RL. Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive neph-ropathy in mice. J Clin Invest. 1999;103:39-46.
Kagami S, Border WA, Miller DE, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-γ expression in rat glomerular mesangial cells. J Clin Invest. 1994;93:2431-7.
Sauter M, Cohen CD, Wörnle M, Mussack T, Ladurner R, Sitter T. ACE inhibitor and AT1-receptor blocker attenuate the production of VEGF in mesothelial cells. Perit Dial Int. 2007;27:167-72.
Duman S, Sen S, Duman C, Oreopoulos DG. Effect of valsartan versus lisinopril on peritoneal sclerosis in rats. Int J Artif Organs. 2005;28:156-63.
Jing S, Kezhou Y, Hong Z, Qun W, Rong W. Effect of renin–angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patients. Nephrology 2010;15:27-32.
Kolesnyk I, Noordzij M, Dekker FW, Boeschoten EW, Krediet RT. Treatment with angiotensin II inhibitors and residual renal function in peritoneal dialysis patients. Perit Dial Int. 2011;31:53-9.
Kolesnyk I, Dekker FW, Noordzij M, le Cessie S, Struijk DG, Krediet RT. Impact of ACE inhibitors and AII receptor blockers on peritoneal membrane transport characteristics in long-term peritoneal dialysis patients. Perit Dial Int. 2007;27:446-53.
Kolesnyk I, Noordzij M, Dekker FW, Boeschoten EW, Krediet RT. A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients. Nephrol Dial Transplant. 2009;24:272-7.
Nishimura H, Ito Y, Mizuno M, Tanaka A, Morita Y, Maruyama S, et al. Mineralocorticoid receptor blockade ameliorates peritoneal fibrosis in new rat peritonitis model. Am J Physiol Renal Physiol. 2008;294:F1084-93.
Heimbürger O. Lipid disorders, statins and the peritoneal membrane. Contrib Nephrol. 2009;163:177-82.
Haslinger B, Goedde MF, Toet KH, Kooistra T. Simvastatin increases fibrinolytic activity in human peritoneal meso¬thelial cells independent of cholesterol lowering. Kidney Int. 2002;62:1611-19.
Haslinger B, Kleemann R, Toet KH, Kooistra T. Simvas-tatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-γ-activat human peritoneal mesothelial cells. Kidney Int. 2003;73:2065-74.
Aarons CB, Cohen PA, Gower A, Reed KL, Leeman SE, Stucchi AF, et al. Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by
increasing peritoneal fibrinolytic activity. Ann Surg. 2007;245:176-84.
Patel S, Mason RM, Suzuki J, Imaizumi A, Kamimura T, Zhang Z. Inhibitory effect of statins on renal epithelial-to-mesenchymal transition. Am J Nephrol. 2006;26:381-7.
Duman S, Sen S, Sozmen EY, Oreopoulos DG. Atorvastatin improves peritoneal sclerosis induced by hypertonic PD solution in rats. Int J Artif Organs. 2005;28:170-6.
Iñiguez MA, Rodríguez A, Volpert OV, Fresno M, Redondo JM. Cyclooxygenase-2: a therapeutic target in angiogenesis. Trends Mol Med. 2003;9:73-8.
Fabbrini P, Schilte MN, Zareie M, ter Wee PM, Keuning ED, Beelen RH, et al. Celecoxib treatment reduces peritoneal fibrosis and angiogenesis and prevents ultrafiltration failure in experimental peritoneal dialysis. Nephrol Dial Transplant. 2009;24:3669-76.
Zemel D, Struijk DG, Dinkla C, Stolk LM, ten Berge IJ, Krediet RT. Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in dialysate and peritoneal membrane characteristics during peritonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med. 1995;126:204-15.
Zhang Y, Kong J, Deb DK, Chang A, Li YC. Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system. J Am Soc Nephrol 2010;21:966–73.
Cunningham J, Zehnder D. New vitamin D analogs and changing therapeutic paradigms. Kidney Int. 2011;9:702-7.
Guerrero F, Montes de Oca A, Aguilera–Tejero E, Zafra R, Rodríguez M, López I. The effect of vitamin D derivatives on vascular calcification associated with inflammation. Nephrol Dial Transplant. 2012;27:2206-12.
Loureiro J, Schilte M, Aguilera A, Albar–Vizcaíno P, Ramírez–Huesca M, Pérez–Lozano ML, et al. BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure. Nephrol Dial Transplant. 2010;25:1098-108.
Krediet RT, Lindholm B, Rippe B. Pathophysiology of peritoneal membrane failure. Perit Dial Int. 2000;20(Suppl 4):S22-42.
Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J Clin Oncol. 2007;25:884-96.
Günal AI, Celiker H, Akpolat N, Ustündag B, Duman S, Akcicek F. By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution. Perit Dial Int. 2002;22:301-6.
Fang CC, Yen CJ, Chen YM, Shyu RS, Tsai TJ, Lee PH, et al. Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta. Kidney Int. 2000;57:2626-33.
Hung KY, Chen CT, Huang JW, Lee PH, Tsai TJ, Hsieh BS. Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells. Kidney Int. 2001;60:1249-57.
Williams JD, Topley N, Craig KJ, Mackenzie RK, Pischetsrieder M, Lage C, et al. The Euro-Balance Trial: theeffect of a new biocompatible peritoneal dialysis fluid (Balance) on the peritoneal membrane. Kidney Int. 2004;66:408-18.
Bajo MA, Selgas R, Castro MA, del Peso G, Díaz C, Sánchez-Tomero JA, et al. Icodextrin effluent leads to a greaterproliferation than glucose effluent of human mesothelialcells studied ex vivo. Perit Dial Int. 2000;20:742-7.
Le Poole CY, Welten AG, Weijmer MC, Valentijn RM, vanIttersum FJ, Ter Wee PM. Initiating CAPD with a regimenlow in glucose and glucose degradation products, withicodextrin and amino acids (NEPP) is safe and efficacious. Perit Dial Int. 2005;25(Suppl 3):S64-8.
