The mechanism of increased renal susceptibility to toxic substances in the elderly Part I: The role of increased vasoconstriction

Springer Science and Business Media LLC - Tập 32 - Trang 539-547 - 2001
Mirjana Jerkić1, Srećko Vojvodić1, José Miguel López-Novoa1
1Instituto Reina Sofia de Investigacióon Nefrológica, Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain

Tóm tắt

The mechanisms of increased susceptibility to nephrotoxins inaging are complex and incompletely understood. It is very important to try to increase our knowledge of them because adults become increasingly vulnerable to nephrotoxic substances, as they grow older. In addition, the percentage of elderly people will increase markedly in the near future, at least in the developed countries. Drugs such as diuretics, laxatives, NSAIDs,aminoglycosides and other nephrotoxic antibiotics, and converting enzyme inhibitors are used a lot by aging people and can produce severe renal problems. Beside drugs, the clinical use of radiocontrast agents also rises in older patients. It seems that the main mechanism of the increased renal susceptibility to toxic substances in the elderly is a disbalance between vasoconstrictorand vasodilator factors (in favor of vasoconstrictor ones).Increased propensity to vasoconstriction (to Ang II, ET and PAF),as well as increased levels of oxidatively modified biomolecules in the elderly, may enhance susceptibility of old kidney to toxic substances. In addition, all mechanisms that influence both mesangial and fibroblast cell proliferation and over-production of extracellular matrix might also be involved in the processes that make the old kidney prone to drug-induced chronic toxic injury.

Tài liệu tham khảo

Meyer BR. Renal function in aging. J Am Geriatr Soc 1989 Aug; 37(8): 791–800. Baylis C, Corman B. The aging kidney: Insights from experimental studies. J Am Soc Nephrol 1998 Apr; 9(4): 699–709. Epstein M. Aging and the kidney. J Am Soc Nephrol 1996 Aug; 7(8): 1106–1122. Chan R, Michelis MF. Nephrologic complications of drug therapy in the elderly. Geriatric Nephrology and Urology 1998; 8(8): 29–44. Pascual J, Orofino L, Liaño F, Marcén R, Naya MT, Orte L, Ortuño J. Incidence and prognosis of acute renal failure in older patients. J Am Geriatr Soc 1990 Jan; 38(1): 25–30. Goldstein RS, Tarloff JB, Hook JB. Age-related nephropathy in laboratory rats. FASEB J 1988; 2: 2241–2251. Rodríguez-Puyol D. The aging kidney. Kidney Int 1998 Dec; 54(6): 2247–2265. Jassal SV, Oreopoulos DG. The aging kidney. Geriatr Nephrol Urol 1998; 8(3): 141–147. López-Novoa JM, Montañes I. Changes in renal function and morphology in aging laboratory animals. In: Macias Nuñez JF, Cameron JS, editors. Renal function and disease in the elderly. London, Boston, Singapore, Sydney, Toronto: Butterworths & Co. Ltd., 1987: 162–183. Macías-NÚñez JF, López-Novoa JM, Martínez-Maldonado M. Acute renal failure in the aged. Semin Nephrol 1996 Jul; 16(4): 330–338. Flamenbaum W. Diuretic use in the elderly: Potential for diuretic-induced hypokalemia. Am J Cardiol 1986 Jan; 57(2): 38A–43A. Hämmerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamic changes in the elderly: Clinical implications. Clinical Pharmacokinetics 1998; 35: 49–64. Bailey RB, Jones SR. Chronic salicylate intoxication. A common cause of morbidity in the elderly. J Am Geriatr Soc 1989 Jun; 37(6): 556–561. Cuny G, Royer RJ, Mur JM, Serot JM, Faure G, Netter P, Maillard A, Penin F. Pharmacokinetics of salicylates in elderly. Gerontology 1979; 25(1): 49–55. Dzgoeva FU, Kutyrina IM, Burgova EN, Salbiev KD, Vanin AF. Decrease in kidney nitric oxide formation detected by electron paramagnetic resonance in acute renal failure due to contrast media. Nephron 1999; 81: 441. Druml W, Lax F, Grimm G, Scheeweiss B, Lenz K, Laggner AN. Acute renal failure in the elderly 1975-1990. Clin Nephrol 1994; 41(6): 342–349. Sabbatini M, Sansone G, Uccello F, De Nicola L, Giliberti A, Sepe V, Magri P, Conte G, Andreucci VE. Functional versus structural changes in the pathophysiology of acute ischemic renal failure in aging rats. Kidney Int 1994 May; 45(5): 1355–1361. Peters-Volleberg GW, Dortant PM, Speijers GJ. Comparison of tobramycin nephrotoxicity in young adult and aged female rats. Pharmacol Toxicol 1999; 84(4): 147–153. Zhong Z, Arteel GE, Connor HD, Yin M, Frankenberg MV, Stachlewitz RF, Raleigh JA, Mason RP, Thurman RG. Cyclosporine A increases hypoxia and free radical production in rat kidneys: Prevention by dietary glycine. Am J Physiol 1998 Oct; 275(Pt 2): F595–F604. Greenfeld Z, Peleg I, Brezis M, Rosen S, Pisanty S. Potential interaction between prolonged cyclosporin administration and aging in the rat kidney. Ann NY Acad Sci 1994 Oct; 717: 209–212. Bennett WM, Lindsley J, Buss WC. The effect of age and dosage route on experimental cyclosporine nephrotoxicity. Transplantation 1991 March; 51(3): 730–731. Stein HJ, Lifschitz DM, Barnes BL. Current concepts on the pathophysiology of acute renal failure. Am J Physiol 1978; 234: F171–F181. Hayes JM, OConnell SNB, Siegel L, Pryce FH, Schreiner GE. Renal renin and renin release in acute renal failure in the rat. Federation Proc 1968; 27: 629. Weidmann P, De Myttenaere-Bursztein S, Maxwell MH, De Lima J. Effect on aging on plasma renin and aldosterone in normal man. Kidney Int 1975 Nov; 8(5): 325–333. Corman B, Barrault MB, Klingler C, Houot AM, Michel JB, Della Bruna R, Pinet F, Soubrier F. Renin gene expression in the aging kidney: Effect of sodium restriction. Mech Ageing Dev 1995 Sep; 84(1): 1–13. Jover B, Dupont M, Geelen G, Wahba W, Mimran A, Corman B. Renal and systemic adaptation to sodium restriction in aging rats. Am J Physiol 1993 May; 264(Pt 2): R833–R838. Hung L, Richardson A. The effect of aging on the genetic expression of renin by mouse kidney. Aging (Milano) 1993 Jun; 5(3): 193–198. Jung FF, Kennefick TM, Ingelfinger JR, Vora JP, Anderson S. Down-regulation of the intrarenal renin-angiotensin system in the aging rat. J Am Soc Nephrol 1995 Feb; 5(8): 1573–1580. Magro AM, Rudofsky UH. Plasma renin activity decrease precedes spontaneous focal glomerular sclerosis in aging rats. Nephron 1982; 31(3): 245–253. Baylis C, Engels K, Hymel A, Navar LG. Plasma renin activity and metabolic clearance rate of angiotensin II in the unstressed aging rat. Mech Ageing Dev 1997 Aug; 97(2): 163–172. Lü X, Li X, Li L, Li L, Li C, Wang H. Variation of intrarenal angiotensin II and angiotensin II receptors by acute renal ischemia in the aged rat. Ren Fail 1996 Jan; 18(1): 19–29. Ferder L, Inserra F, Romano L, Ercole L, Pszenny V. Effects of angiotensin-converting enzyme inhibition on mitochondrial number in the aging mouse. Am J Physiol 1993 Jul; 265(Pt 1): C15–C18. Heudes D, Michel O, Chevalier J, Scalbert E, Ezan E, Bariety J, Zimmerman A, Corman B. Effect of chronic ANG Iconverting enzyme inhibition on aging processes. I. Kidney structure and function. Am J Physiol 1994 Mar; 266(Pt 2): R1038–R1051. Corman B, Michel JB. Renin-angiotensin system, convertingenzyme inhibition, and kidney function in aging female rats. Am J Physiol 1986 Sept; 251(Pt 2): R450–R455. Baylis C. Renal responses to acute angiotensin II inhibition and administered angiotensin II in the aging, conscious, chronically catheterized rat. Am J Kidney Dis 1993 Dec; 22(6): 842–850. Tank JE, Vora JP, Houghton DC, Anderson S. Altered renal vascular responses in aging rat kidney. Am J Physiol 1994 Jun; 266(Pt 2): F942–F948. Tomita K, Ujie K, Nakanishi T, Tomura S, Matsuda O, Ando K, Shichiri M, Hirata Y, Marumo F. Plasma endothelin levels in patients with acute renal failure. [letter] N Engl JMed 1989; 321: 1127. López-Farré A, Gómez-Garre D, Bernabeu F, López-Novoa JM. A role for endothelin in the maintenance of postischaemic renal failure in the rat. J Physiol (Lond) 1991 Dec; 444: 513–522. Jerkić M, Varagic J, Jovovic DJ, Nastic-Miric D, Adanja-Grujic G, Radujkovic-Kuburovic G, Vukobratovic S, Miloradovic Z, Veljkovic V. Role of nitric oxide in postischemic experimental acute renal failure. In: Moncada S, Toda N, Maeda H, Higgs EA, editors. The Biology of nitric oxide - Part 6. London: Portland Press Ltd, 1998: 226. Lanese DM, Falk SA, Conger JD. Sequential agonist activation and site-specific mediation of acute cyclosporine constriction in rat renal arterioles. Transplantation 1994 Dec; 58(12): 1371–1378. Fogo A, Hellings SE, Inagami T, Kon V. Endothelin receptor antagonism is protective in in vivo acute cyclosporine toxicity. Kidney Int 1992 Feb; 42: 770–774. Hocher B, Rohmeiss P, Diekmann F, Zart R, Vogt V, Schiller S, Bauer C, Koppenhagen K, Distler A, Gretz N. Distribution of endothelin receptor subtypes in the rat kidney. Renal and haemodynamic effects of the mixed (A/B) endothelin receptor antagonist bosentan. Eur J Clin Chem Clin Biochem 1995 Aug; 33(8): 463–472. Kumazaki T, Fujii T, Kobayashi M, Mitsui Y. Aging-and growth-dependent modulation of endothelin-1 gene expression in human vascular endothelial cells. Exp Cell Res 1994 Mar; 211(1): 6–11. Greenfeld Z, Engels K, Samsell L, Baylis C. The role of endothelin in the age dependent increase in renal vascular resistance in the rat kidney. Mech Ageing Dev 1998; 101(1-2): 145–152. López-Novoa JM. Potential role of platelet activating factor in acute renal failure. Kidney Int 1999; 55: 1672–1682. López-Farré A, Ramón y Cajal S, Braquet P, López-Novoa JM. Platelet activating factor antagonist protect against postischaemic acute renal failure in the rats. J Pharmacol Exp Ther 1990; 253: 328–333. Rodrígez Puyol D, Lamas S, Olivera A, López-Farré A, Ortega G, Hernando L, López-Novoa JM. Action of cyclosporin A on cultured rat mesangial cells. Kidney Int 1989 Jan; 35(1): 632–637. Dos Santos POF, Boim MA, Barros EJG, Schor N. Role of platelet activating factor in gentamicin and cisplatin nephrotoxicity. Kidney Int 1991 Oct; 40(4): 742–747. Martínez-Salgado C, Rodríguez-Barbero A, Rodríguez-Puyol D, Pérez de Lema G, López-Novoa JM. Involvement of phospholipase A2 in gentamicin-induced rat mesangial cell activation Am J Physiol 1997 Jul; 273(Pt 2): F60–F66. Ruiz-Torres P, Gonzales-Rubio M, Lucio-Casaña FJ, Ruiz-Villaespesa A, Rodrigez-Puyol M, Rodrigez-Puyol D. Reactive oxygen species and platelet activating factor synthesis in age-related glomerulosclerosis. J Lab Clin Med 1994; 124: 489–495. Abete P, Ferrara N, Leosco D, Caccese P, Landino P, Sederino S, Balbi R, Rengo F. Age-related effects of platelet activating factor (PAF) in the isolated perfused rat heart. J Mol Cell Cardiol 1992 Dec; 24(12): 1399–1407. Bock AH. Pathogenesis of acute renal failure: New aspects. Nephron 1997; 76: 130–142. Duque I, García-Escribano C, Rodríguez-Puyol M, Díez-Marqués ML, López-Novoa JM, Arribas I, Hernando L, Rodríguez-Puyol D. Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli. Am J Physiol 1992 Sep; 263(Pt 2): F466–F473. Hughes AK, Stricklett PK, Padilla E, Kohan DE. Effect of reactive oxygen species on endothelin-1 production by human mesangial cells. Kidney Int 1996 Jan; 49(1): 181–189. Paller MS, Hoidal JR, Ferris TF. Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 1984 Oct; 74(4): 1156–1164. Parra T, de Arriba G, Arribas I, Perez de Lema G, Rodriguez-Puyol D, Rodriguez-Puyol M. Cyclosporine A nephrotoxicity: Role of thromboxane and reactive oxygen species. J Lab Clin Med 1998 Jan; 131(1): 63–70. Perez de Lema G, Arribas-Gómez I, Ruiz-Ginéz JA, De Arriba G, Prieto A, Rodríguez-Puyol D, Rodríguez-Puyol M. Reactive oxygen species mediate the effects of cyclosporine A on human cultured mesangial cells. Transplant Proceed 1997 Feb/March; 29(1/2): 1241–1243. Schöneich C. Reactive oxygen species and biological aging: A mechanictic approach. Exp Gerontol 1999 Jan; 34(1): 19–34. Fridovich I. Superoxide anion radical (O –2 ), superoxide dismutases, and related matters. J Biol Chem 1997 Jul; 272(30): 18515–18517. Congy F, Bonnefont-Rousselot D, Dever S, Delattre J, Emerit J. Study of oxidative stress in the elderly. Presse Med 1995 Jul; 24(24): 1115–1118. Ruiz-Torres MP, Bosch RJ, O'valle F, Del Moral RG, Ramírez C, Masseroli M, Pérez-Caballero C, Iglesias MC, Rodrígez Puyol M, Rodrígez Puyol D. Age-related increase in expression of TGF-?1 in the rat kidney: Relationship to morphologic changes. J Am Soc Nephrol 1998 May; 9(5): 782–791. Doi T, Vlassara H, Kirstein M, Yamada Y, Striker G, Striker L. Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor. Proc Natl Acad Sci USA 1992 Apr; 89(7): 2873–2877. Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: Biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 1994; 70: 138–151. Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995; 46: 223–234. Li YM, Steffes M, Donnelly T, Liu C, Fuh H, Basgen J, Bucala R, Vlassara H. Prevention of cardiovascular and renal pathology of aging by the advanced glycation inhibitor aminoguanidine. Proc Natl Acad Sci USA 1996 Apr; 93(9): 3902–3907. Reckelhoff JF, Hennington BS, Kanji V, Racusen LC, Schmidt AM, Yan SD, Morrow J, Roberts LJ II, Salahudeen AK. Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats. Am J Hypertens 1999 May; 12(5): 492–498.