Pharmacy World and Science

, Volume 18, Issue 6, pp 204–210

ACE inhibitors and proteinuria

  • R. T. Gansevoort
  • D. de Zeeuw
  • P. E. de Jong
Reviews

Abstract

This review discusses the clinical consequences of uninary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibitors have been shown to reduce proteinuria more effectively than other antihypertensives. Their antiproteinuric effect seems to be independent of the underlying renal disease, and is mediated by a specific, not yet fully elucidated mechanism. Urinary protein loss related phenomena, such as hypoalbuminemia and aberrant lipoprotein profile, tend to improve also during ACE inhibitor treatment. Furthermore, ACE inhibition has been shown to prevent the renal function deterioration that is frequently observed in patients with renal disease. Interestingly, it has recently been shown that in proteinuric patients with renal disease the initial proteinuria lowering response to ACE inhibition predicts long-term renal function outcome during this treatment: the more proteinuria is lowered during the first months, the better renal function will be preserved over the following years. Because of these favorable effects ACE inhibitors have become a widely used class of agents in nephrology. They are not only prescribed for lowering blood pressure in the hypertensive renal patient, but also as symptomatic treatment of patients with proteinuria, and to prevent renal function loss in patients with both diabetic and non-diabetic renal disease.

Keywords

Albuminuria Angiotensin II Angiotensin-converting enzyme inhibitors Bradykinin Glomerular flitration rate Nephrotic syndrome Proteinuria Renal circulation Review 

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References

  1. 1.
    PrinsE.J.L., HoorntjeS.J., WeeningJ.J., DonkerA.J.M.: Nephrotic syndrome in a patient on captopril, Lancet 1979, ii: 306.Google Scholar
  2. 2.
    HoorntjeS.J., WeeningJ.J., KallenbergC.G.M., DonkerA.J.M.: Serum-sickness-like syndrome with membranous glomerulopathy in patients on captopril. Lancet 1979;ii:1297.Google Scholar
  3. 3.
    HoorntjeS.J., WeeningJ.J., PrinsE.J.L., DonkerA.J.M.: Membranous glomerulopathy in a patient on captopril, Acta Med Scand 1980;208:325.Google Scholar
  4. 4.
    CaseD.B., AtlasS.A., MouradianJ.A. FishmanR.A., ShermanR.L., LaraghJ.H.: Proteinuria during long-term captopril therapy, JAMA 1980;244:346–349.Google Scholar
  5. 5.
    SturgillB.C., ShearlockK.T.: Membranous glomerulopathy and nephrotic syndrome after captopril therapy, JAMA 1983;250:2343–2345.Google Scholar
  6. 6.
    IslesC.G., HodsmanG.P., RobertsonJ.I.S.: Side-effects of captopril, Lancet 1983;i:355.Google Scholar
  7. 7.
    Captopril Collaborative Study Group: Does captopril cause renal damage in hypertensive patients? Lancet 1982;i:988–990.Google Scholar
  8. 8.
    GroelJ.I., TodrosS.S., DreslinskiG.R., JenkinsA.C.: Long-term antihypertensive therapy with captopril, Hyperten 1983;145(53):5.Google Scholar
  9. 9.
    SimonG., MoriokaS., SnyderD.K., CohnJ.N.: Increased renal plasma flow in long-term enalapril treatment of hypertension, Clin Pharmacol Ther 1983;34:459–465.Google Scholar
  10. 10.
    HerlitzH., EdenoC., MulecH., WestbergG., AurellM.: Captopril treatment of hypertension and renal failure in systemic lupus erythematosus, Nephron 1984;38:253–256.Google Scholar
  11. 11.
    TagumaY., KitamotoY., FutakiG., UedaH., MonmaH., IshizakiM.. Effect of captopril on heavy proteinuria in azotemic diabetes, N Engl J Med 1985;313:1617–1620.Google Scholar
  12. 12.
    HeegJ.E., deJongP.E., van deHemG.K., deZeeuwD.: Reduction of proteinuria by angiotensin converting enzyme inhibition, Kidney Int 1987;32:78–83.Google Scholar
  13. 13.
    BrazyP.C., SteadW.W., fitzwilliamJ.F.: Progression of renal insufficiency: Role of blood pressure, Kidney Int 1989;35:670–674.Google Scholar
  14. 14.
    VibertiG.C.: Prognostic significance of microalbuminuria, Am J Hypertens 1994;7:69s-72s.Google Scholar
  15. 15.
    HuntL.P., ShortC.d., MallickN.P.: Prognostic indicators in patients presenting with the nephrotic syndrome, Kidney Int 1988;34:382–388.Google Scholar
  16. 16.
    WilliamsP.S., FassG., BoneJ.M.: Renal pathology and proteinuria determine progression in untreated mild/moderate chronic renal failure, QJ Med 1988;67:343–354.Google Scholar
  17. 17.
    KlahrS., LeveyA.S., BeckG.J., GaggiulaA.W., HunsickerL., KusekJ.W., StrikerG.: The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease, New Engl J Med 1994;330:877–884.Google Scholar
  18. 18.
    RemuzziG., BertaniT.: Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int 1990;38:384–394.Google Scholar
  19. 19.
    SamuelssonO., WihelmsenL., ElmferdtD., PennertK., WedelH., WidstrandJ., BerglundG.: Predictors of cardiovascular morbidity in treated hypertension, results from the primary preventive trial in Goteborg, Sweden, J Hypertens 1985;3:167–176.Google Scholar
  20. 20.
    KannelW.B., StampferM.J., CastelliW.P., VerterJ.: The prognostic significance of proteinuria, The Framingham Study, Am Heart J 1984;108:1347–1352.Google Scholar
  21. 21.
    BulpittC.J., BeeversD.G., ButlerA., ColesE.C., HuntD., Munro-Faurea.D., NewsonR.B.: The survival of treated hypertensive patients and their causes of death: a report from the DHSS hypertensive care computing project (DHCCP), J Hypertens 1986;4:93–99.Google Scholar
  22. 22.
    YudkinS.J., ForrestR.D., JacksonC.: Microalbuminuria as a predictor of vascular disease in non-diabetic subjects, Lancet 1988;ii:530–533.Google Scholar
  23. 23.
    DamsgaardE.M., FrolandA., Jorgensen MogensenC.E.: Microalbuminuria as predictor of increased mortality in elderly people, Br Med J 1990;300:297–300.Google Scholar
  24. 24.
    SamuelssonO.: Proteinuria as a prognostic factor during long term hypertensive care, Drugs, 35, S5 48–54, 1988.Google Scholar
  25. 25.
    RitzE., NowickiM., FlislerD., HornerD., KlimmH.P.: Proteinuria and hypertension, Kidney Int 1994;46S47,S76-S80.Google Scholar
  26. 26.
    MogensenC.E.: Micro-albuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes, N Engl Med 1986;310:356–360.Google Scholar
  27. 27.
    JarretR.J., VibertiG.C., ArgyropoulosA., HillR.D., MahmudU., MurrelsT.J.: Microalbuminuria predicts morfality in non-insulin dependent diabetes, Diabetic Med 1984;1:17–19.Google Scholar
  28. 28.
    SchmitzA., VaethM.: Micro-albuminuria: a major risk factor in non insulin dependent diabetes. A 10 year follow-up of 503 patients, Diabetic Med 1988;5:126–134.Google Scholar
  29. 29.
    OrdonezJ.d., HiattR.A., KillebrewE.J., FirmenaB.H.: The increased risk of coronary heart disease associated with nephrotic syndrome, Kidney Int 1993;44:638–642.Google Scholar
  30. 30.
    GansevoortR.T., SluiterW., HemmelderM.H., deZeeuwD., deJongP.E.: The antiproteinuric effect of blood pressure lowering agents: a meta-analysis of comparative trials, Neprhol Dial Transplant 1995 (in press); 10:11.Google Scholar
  31. 31.
    FlorettoP., FrigatoF., VelussiM., RivaF., MuolloB., CarraroA.: Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action on albumin excretion rate in hypertensive insulin-dependent diabetic patients, Am J Hypertens 1992;5:37–846.Google Scholar
  32. 32.
    DemarieB.K., BakrisG.L.: Effects of different calcium antagonists on proteinuria associated with diabetes mellitus, Annals Int Med 1990;113:987–988.Google Scholar
  33. 33.
    WightJ.P., BrownC.B., ElNahasA.M.: Short-term effects of calcium antagonists on renal hemodynamics in patients with chronic renal failure, Nephron 1991;58:62–67.Google Scholar
  34. 34.
    KasiskeB.L., KalilR.S.N., MaJ.Z., LiaoM., KeaneW.F.: Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis, Annals Int Med 1993;118:129–138.Google Scholar
  35. 35.
    WeidmannP., BoehlenL.M., deCourtenM.: Effects of different antihypertensive drugs on human diabetic proteinuria, Neprhol Dial Transplant 1993;8:582–584.Google Scholar
  36. 36.
    AndersonS., MeyerT.W., RennkeH.G., BrennerB.M.: Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass, J Clin Invest 1985;76:612–619.Google Scholar
  37. 37.
    AriszL., DonkerA.J.M., BrentjensJ.R.H., van derHemG.K.: The effect of indomethacin on proteinuria and kidney function in the nephrotic syndrome, Acta Med Scand 1976;199:122–125.Google Scholar
  38. 38.
    DonkerA.J.M., BrentjensJ.R.H., van derHemG.K., AriszL.: Treatment of the nephrotic syndrome with indomethacin, Nephron 1978;22:374–381.Google Scholar
  39. 39.
    RosenbergM.E., SwansonJ.E., ThomasB.L., HostetterT.H.: Glomerular and hormonal responses to dietary protein intake in human renal disease, Am J Physiol 1987;253:F1083-F1090.Google Scholar
  40. 40.
    WetzelsJ.F.M., HoitsmaA.J., BerdenJ.H.M., KoeneR.A.P.: Renal hemodynamic effects of a short-term high protein and low protein diet in patients with renal disease, Clin Neprhol 1988;30:42–47.Google Scholar
  41. 41.
    OlmerM., PainC., DussolB., BerlandY.: Protein diet and nephrotic syndrome, Kidney Int 1989;36:S152-S153.Google Scholar
  42. 42.
    HeegJ.E., deJongP.E., deZeeuwD.: Additive antiproteinuretic effect of angiotensin converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy: a clue to the mechanism of action, Clinical Science 1991;81:367–372.Google Scholar
  43. 43.
    GansevoortR.T., deZeeuwd., deJongP.E.: Additive antiproteinuretic effect of ACE inhibition and a low protein diet in human renal disease, Nephrol Dial Transplant 1995;10:497–504.Google Scholar
  44. 44.
    RuilopeL.M., CasaiM.C., PragaM., AlcazarJ.M., DecapG., LaheraV., RodicioJ.L.: Additive antiproteinuric effect of converting enzyme inhibition and a low protein intake, J. Am Soc Nephrol 1992;3:1307–1311.Google Scholar
  45. 45.
    AllonM., PasqueC.b., RodriguezM.: Acute effects of captopril and ibuprofen in patients with nephrosis, J Lab Clin Med 1990;116:462–468.Google Scholar
  46. 46.
    HeegJ.E., deJongP.E., van derHemG.K., deZeeuwD.: Angiotensin II does not acutely reverse the reduction of proteinuria by long-term ACE inhbition, Kidney Int 1991;40:734–741.Google Scholar
  47. 47.
    GansevoortR.T., deZeeuwD., deJongP.E.: Dissociation between the course of the hemodynamic and antiproteinuric effects of ACE inhibition, Kidney Int 1993;44:579–584.Google Scholar
  48. 48.
    GibbonsG.H., DzauV.J.: the emerging concept of vascular remodelling, New Engl J Med 1994;330:1431–1438.Google Scholar
  49. 49.
    WolfG., NeilsonE.G.: Angiotensin II as a renal growth factor, J Am Soc Nephrol 1993;3:1531–1540.Google Scholar
  50. 50.
    DorerF.E., KahnJ.R., LentzK.E., LevineM., SkeggsL.T.: Hydrolysis of bradykinin by angiotensin converting enzyme, Circ Res 1974;34:824–827.Google Scholar
  51. 51.
    IsrailliZ.H., HallW.D.: Cough and angioneurotic edema associated with angiotensin converting enzyme inhibitor therapy, Ann Intern Med 1992;117:234–242.Google Scholar
  52. 52.
    GavrasI.: Bradykinin mediated effects of ACE inhibition, Kidney Int 1992;42:1020–1029.Google Scholar
  53. 53.
    HutchisonF.N., MartinV.I.: Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome, Am J Physiol 1990;258:F1237-F1244.Google Scholar
  54. 54.
    FenoyF.J., ScicliG., CameteroO., RomanR.J.: Effects of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril, Hypertension 1991;17:1038–1044.Google Scholar
  55. 55.
    Hajj-AliA.F., ZimmermanB.G.: Kinin contribution to renal vasodilator effect of captopril in rabbits, Hypertension 1991;17:504–509.Google Scholar
  56. 56.
    GansevoortR.T., deZeeuwD., deJongP.E.: Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin angiotensin system? Kidney Int 1994;45:861–867.Google Scholar
  57. 57.
    RhalebN.E., RouissiN., NantelF., D'Orleans-JusteP., RegoliD.: Dup 753 is a specific antagonist for the angiotensin receptor, Hypertension 1991;17:480–484.Google Scholar
  58. 58.
    HeegJ.E., deJongP.E., van derHemG.K., deZeeuwD.: Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril, Kidney Int 1989;36:272–279.Google Scholar
  59. 59.
    GansevoortR.T., deZeeuwD., deJongP.E.: Long-term benefits of the antiproteinuric effect of ACE inhibition in nondiabetic renal disease, Am J Kidney Dis 1993;2:202–206.Google Scholar
  60. 60.
    ButerH., HemmelderM.H., deZeeuwD., deJongP.E.: HCT potentiates the effect of ACE inhibition comparable to a low sodium diet, J Am Soc Nephrol 1995;6:420.Google Scholar
  61. 61.
    KnausW.A., WagnerD.P., DraperE.A., ZimmermanJ.E., BergmanM., BastosP.G.: The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults, Chest 1991;100:1619–1636.Google Scholar
  62. 62.
    MarikP.E.: The treatment of hypoalbuminemia in the critically ill patient, Heart Lung 1993;22:166–170.Google Scholar
  63. 63.
    AppelG.B., BlumC.B., ChienS., KunisC.L., AppelA.S.: the hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure and viscosity, N Engl J Med 1985;312:1544–1548.Google Scholar
  64. 64.
    JovenJ., VillabonaC., VilellaE., MasanaL., AlbertiR., VallesM.: Abnormalities of lipoprotein metabolism in patients with the nephrotic syndrome, N Engl J Med 1990;323:579–584.Google Scholar
  65. 65.
    KaradiO., RomicsL., PalosG., DomanJ., KaszasI., HeszA., KostnerG.M.: Lp (a) lipoprotein concentration in serum of patients with heavy proteinuria of different origin, Clin Chem 1989;35:2121–2123.Google Scholar
  66. 66.
    KeilaniT., SchlueterW.A., LevinM.L., GatlleD.C.: Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor, Annals Int Med 1993;118:246–254.Google Scholar
  67. 67.
    KeaneW.F., KasiskeB.L.: Hyperlipidemia in the nephrotic syndrome, N Engl J Med 1990;323:603–604.Google Scholar
  68. 68.
    Wanner, C., Bohler, J., Eckhardt, H.G., Wieland, H., Schollmeyer, P.: Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome, Clin Nephrol 1993; in press:39.Google Scholar
  69. 69.
    GansevoortR.T., HeegJ.E., DikkescheiB.D., deZeeuwd., deJongP.E., DullaartR.P.F.: Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria, Nephrol Dial Transplant 1994;9:244–250.Google Scholar
  70. 70.
    RabelinkA.J., HeneR.J., ErkelensD.W., JolesJ.A., KoomansH.A.: Effect of simvastatin and cholestyramine on lipoprotein profile in hyperlipidemia of nephrotic syndrome, Lancet 1988;ii:1335–1338.Google Scholar
  71. 71.
    ThomasM.E., FreestoneA., VargheseZ., PersaudJ.W., MoorheadJ.M.: Lipoprotein (a) in patients with proteinuria, Neprhol Dial Transplant 1992;7:597–601.Google Scholar
  72. 72.
    WarwickG.L., PackardC.J., MurrayL., GriersonD., StewartJ.P., ShepherdJ., Boulton-JonesJ.M.: Effect of simvastatin on plasma lipid and lipoprotein concentrations and low-density lipoprotein metabolism in the nephrotic syndrome, Clinical Science 1992;82:701–708.Google Scholar
  73. 73.
    BjorckS., Nybergg., MulecH., GranerusG., HerlitzH., AurellM.: Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy, Br Med J 1986;293:471–474.Google Scholar
  74. 74.
    ParvingH.H., AndersenA.R., SmidtU.M., HommelE., MathiesenE.R., SvendsenP.A.: Effect of antihypertensive teatment on kidney function in diabetic nephropathy, Br Med J 1987;294:1443–1447.Google Scholar
  75. 75.
    BrazyP.C., FitzwilliamJ.F.: Progressive renal disease: role of race and antihypertensive medications, Kidney Int 1990;37: 1113–1119.Google Scholar
  76. 76.
    LewisE.J., HunsickerL.G., BainR.P., RohdeR.D.: The effect of angiotensin converting enzyme inhibition on diabetic nephropathy, N Engl J Med 1993;329:1456–1462.Google Scholar
  77. 77.
    HannedoucheT., LandaisP., GoldfarbB., ElEsperN., Fourniera., GodinM., DurandD., ChanardJ., MignonF., SucJ-M., GrunfeldJ.P.: Randomised controlled trial of enalapril and beta-blockers in non-diabetic chronic renal failure, BMJ 1994;309:833–837.Google Scholar
  78. 78.
    MaschioG., AlbertiD., JaninG., LocatelliF., MannJ.F.E., MotoleseM., PonticelliC., RitzE., ZuchelliP.: Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency, N Engl J Med 1996 1996;334:939–945.Google Scholar
  79. 79.
    PragaM., HernandezE., MontoyoC., AndresA., RuilopeL.M., RodicioJ.L.: Long-term beneficial effects of ACE inhibition in patients with nephrotic proteinuria, Am J Kidney Dis 1992;20:240–248.Google Scholar
  80. 80.
    RossingP., HommelE., SmidtU.M., ParvingH.H.: Reduction in albuminuria predicts diminished progression in diabetic nephropathy, Kidney Int 1994;45:S145-S149.Google Scholar
  81. 81.
    ApperlooA.J., deZeeuwD, deJongP.E.: Short-term antiproteinuric response to antihypertensive treatment predicts long-term GFR decline in patients with non-diabetic renal disease, Kidney Int 1994;45:S174-S178.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • R. T. Gansevoort
    • 1
  • D. de Zeeuw
    • 2
  • P. E. de Jong
    • 2
  1. 1.Twenteborg ZiekenhuisAlmeloThe Netherlands
  2. 2.Division of Nephrology, Department of Internal MedicineState University HospitalGroningenThe Netherlands

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