Clinical Investigation

Kidney International (1993) 43, 419–425; doi:10.1038/ki.1993.61

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants

Georges Mourad1, Jean Ribstein1 and Albert Mimran1

1Department of Medicine and Nephrology, Hôpital Lapeyronie, Montpellier, France

Correspondence: Georges Mourad MD, Nephrologie, Hôpital Lapeyronie, 34059 Montpellier cedex, France.

Received 20 May 1992; Revised 3 August 1992; Accepted 17 September 1993.

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Abstract

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants. The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 plusminus 2 vs. 120 plusminus 4 mm Hg), effective renal plasma flow (285 plusminus 26 vs. 248 plusminus 33 ml/min/1.73 m2) and glomerular filtration rate (59 plusminus 4 vs. 61 plusminus 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 plusminus 3; CA -13 plusminus 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 plusminus 0.01% to 0.19 plusminus 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol. A consistent reduction of arterial pressure by either treatment seems to afford a similar degree of renal protection in long-term cyclosporine treated patients.

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References

  1. Brazy PC, Fitzwilliam JF: Progressive renal disease: Role of race and antihypertensive medications. Kidney Int 37:1113–1119, 1990 | PubMed | ISI | ChemPort |
  2. Luke RG: Pathophysiology and treatment of post-transplant hypertension. J Am Soc Nephrol 2:S37–S44, 1991 | PubMed |
  3. Cheigh JS, Stenzel KHS, Wang J: Hypertension is associated with decreased graft survival in long-term kidney transplant recipients. Transplant Proc 17:174–175, 1985
  4. Schachter M: Cyclosporine A and hypertension. J Hypertens 6:511–516, 1988
  5. Curtis JJ, Luke RG, Dubovsky E, Diethelm AG, Whelchel JD, Jones P: Cyclosporin in therapeutic doses increases renal allograft vascular resistance. Lancet 2:477–479, 1986
  6. Ribstein J, Mourad G, Mion C, Mimran A: Chronic angiotensin converting enzyme inhibition as an alternative to native kidneys removal in post-transplant hypertension. J Hypertens 4 (Suppl 5):S255–S257, 1986
  7. Curtis JJ, Luke RG, Jones PR, Diethelm AG: Hypertension in cyclosporine-treated renal transplant recipients is sodium dependant. Am J Med 85:134–138, 1988 | PubMed | ISI | ChemPort |
  8. Scherrer U, Vissing SF, Morgan BJ, Rollins JA, Tindall RSA, Ring S, Hanson P, Mohanty PK, Victor RG: Cyclosporine-induced sympathetic activation and hypertension after heart transplantation. N Engl J Med 323:693–699, 1990 | PubMed | ISI | ChemPort |
  9. Myers BD, Sibley R, Newton L, Tomlanovich SJ, Boshkos C, Stinson E, Luetscher J, Whitney DJ, Krasny D, Koplon NS, Perlroth MG: The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int 33:590–600, 1988 | PubMed | ISI | ChemPort |
  10. Bantle JP, Nath KA, Sutherland DER, Najarian JS, Ferris TF: Effects of cyclosporine on the renin-angiotensin-aldosterone system and potassium excretion in renal transplant recipients. Arch Intern Med 145:505–508, 1985
  11. Ribstein J, Mourad G, Mimran A: Renal function in cyclosporin-treated kidney transplant recipients: Influence of renin and kal-likrein, in Current Advances in ACE Inhibition, edited by Sever PS, McGregor GA, London, Churchill-Livingstone, 1989, pp. 261–264
  12. Bantle JP, Boudreau RJ, Ferris TF: Suppression of plasma renin activity by cyclosporine. Am J Med 83:59–64, 1987
  13. Murray BM, Paller MS, Ferris TF: Effect of cyclosporine administration on renal hemodynamics in conscious rats. Kidney Int 283:767–774, 1985
  14. Kaskel FJ, Devarajan P, Arbeit LA, Partin JS, Moore LC: Cyclosporine nephrotoxicity: Sodium excretion, autoregulation, and angiotensin II. Am J Physiol 252:F733–F742, 1987 | PubMed | ChemPort |
  15. Dieperink H, Leyssac PP, Starklint H, Jorgensen KA, Kemp E: Antagonist capacities of nifedipine, captopril, phenoxybenzamine, prostacyclin and indomethacin on cyclosporin A induced impairment of renal function. Eur J Clin Invest 16:540–548, 1986
  16. McNally PG, Baker F, Mistry N, Walls J, Feehally J: Effect of nifedipine on renal hemodynamics in an animal model of cyclosporin A nephrotoxicity. Clin Sci 79:259–266, 1990
  17. Orugun EO, Smart LM, Whiting PH: The effect of calcium blockade with verapamil on experimental cyclosporine nephrotoxicity. Transplant Proc 23:354–355, 1991
  18. Mimran A, Deschodt G: The role of the renin-angiotensin system in the hormonal and renal response to tilt in normal man. Renal Physiol 6:36–42, 1983
  19. Tomlanovitch SJ, Myers BD: Limitations of creatinine in quantifying severity of chronic nephropathy due to cyclosporine. Am J Kidney Dis 8:332–337, 1986
  20. Weir MR: Calcium channel blockers in organ transplantation: Important new therapeutic modalities. J Am Soc Nephrol 1:S28–S38, 1990 | ISI |
  21. Bravo EL: Converting enzyme inhibition with an orally active compound in hypertensive man. Hypertension 1:39–46, 1979
  22. Clozel JP, Fischli W: Cyclosporin-induced hypertension in marmosets: A new model of hypertension sensitive to angiotensin-converting enzyme inhibition. J Cardiovasc Pharmacol 14:77–81, 1989
  23. Dzau VJ: Multiple pathways of angiotensin production in the blood vessel wall: Evidence, possibilities and hypotheses. J Hypertens 7:933–936, 1898
  24. Kiowski W, Buhler FR, Fadyoni M, Erne P, Muller FB, Hulther UL, Bolli P: Age, race, blood pressure and renin: Predictors for antihypertensive treatment with calcium antagonists. Am J Cardiol 56 (Suppl):H81–H85, 1986
  25. MacGregeor GA, Cappucio FP, Markandu ND: Sodium intake, high blood pressure and calcium channel blockers. Am J Med 82 (Suppl 3B):16–22, 1987
  26. Dawidson I, Rooth P, Lu C, Sagalowsky A, Diller K, Palmer P, Peters P, Risser R, Sandor Z, Seney F: Verapamil improves the outcome after cadaver renal transplantation. J Am Soc Nephrol 2:983–990, 1991
  27. Dy GR, Raja RM, Mendez MM: The clinical and biochemical effect of calcium channel blockers in organ transplant recipients on cyclosporine. Transplant Proc 23:1258–1259, 1991
  28. Myers BD, Ross J, Newton L, Luetscher J, Perlroth M: Cyclosporine-associated chronic nephropathy. N Engl J Med 311:699–705, 1984 | PubMed | ISI | ChemPort |
  29. Kopp JB, Klotman PE: Cellular and molecular mechanisms of cyclosporin nephrotoxicity. J Am Soc Nephrol 1:162–179, 1990 | PubMed | ISI | ChemPort |
  30. Slomowitz LA, Wilkinson A, Hawkins R, Danovitch G: Evaluation of kidney function in renal transplant patient receiving long-term cyclosporine. Am J Kidney Dis 15:530–534, 1990
  31. Gagnon JA, Keller HI, Kokotis W, Schrier RW: Analysis of the role of the renin angiotensin system in autoregulation of glomerular filtration. Am J Physiol 219:491–496, 1970
  32. Michael UF, Meeks LA, Lee SM: Effects of nitrendipine on renal function: Evidence for interference with tubular uptake of PAH. (abstract) Kidney Int 25:290, 1984
  33. Bourbigot B, Guiserix J, Axiau J, Brossollette JF, Morin JF, Cledes J: Nicardipine increases cyclosporin blood levels. Lancet 2:447, 1986
  34. Grino JM, Sabte I, Castelao AM, Albina J: Influence of diltiazem on cyclosporin clearance. Lancet 1:387, 1986
  35. McMillen MA, Tesi RI, Baemgarten WB, Jaffe BM, Wait IB: Potentiation of cyclosporin by verapamil in vitro. Transplantation 40:444–445, 1985
  36. McNally PG, Walls J, Feehally J: The effect of nifedipine on renal function in normotensive cyclosporin A-treated renal allograft recipients. Nephrol Dial Transplant 5:962–968, 1990
  37. Feehally J, Walls J, Mistry N, Horsburgh T, Taylor J, Veitch PS, Bell PRF: Does nifedipine ameliorate cyclosporin A nephrotoxicity? Br Med J 295:310, 1987
  38. Sun CH, Ward HJ, Wellington LP, Koyle MA, Yanagawa N, Lee DBN: Serum erythropoietin levels after renal transplantation. N Engl J Med 321:151–157, 1989 | PubMed | ISI | ChemPort |
  39. Bakris GL, Sauter ER, Hussey JL, Fisher JW, Gaber AO, Winsett R: Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplantation. N Engl J Med 323:86–90, 1990 | PubMed | ISI | ChemPort |
  40. Wickre CG, Norman DJ, Bennison Z, Barry JM, Bennett WM: Post-renal transplant erythrocytosis: A review of 53 patients. Kidney Int 23:731–737, 1983 | PubMed | ISI | ChemPort |
  41. Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE: Enalapril-associated anemia in renal transplant recipient treated for hypertension. Am J Kidney Dis 17:199–205, 1991 | PubMed | ISI | ChemPort |
  42. Gaston RS, Julian BA, Diethelm AG, Curtis JJ: Effects of enalapril on erythrocytosis after renal transplantation. Ann Intern Med 115:954–955, 1991 | PubMed | ISI | ChemPort |
  43. Islam MS, Bourbigot B, Codet JP, Songy B, Gournier G, Cledes J: Captopril induces correction of post renal transplant erythremia. Transplant Int 3:222–225, 1990
  44. Gould AB, Goodman S, Dewolf R, Onesti G, Swartz C: Interrelation of the renin system and erythropoeitin in rats. J Lab Clin Med 96:523–534, 1980 | PubMed | ISI | ChemPort |

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