Clinical Investigation

Kidney International (1993) 44, 165–172; doi:10.1038/ki.1993.227

Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients

Eric Rondeau, Françoise Paillard, Marie-Noëlle Peraldi, Isabelle Violet, Sophie Tasse, Jean-Claude Dussaule, Raymond Ardaillou and Jean-Daniel Sraer

Service de Néphrologie, and Service d'Explorations Fonctionnelles et INSERM U 64, Hôpital Tenon, Paris; and Institut de Recherche International Servier, Courbevoie, France

Correspondence: Dr Eric Rondeau, Service de Néphrologie A, Hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.

Received 9 October 1992; Revised 25 February 1993; Accepted 1 March 1993.

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Abstract

Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients. To determine the renal functional reserve in renal transplant recipients, we measured the glomerular filtration rate by inulin clearance and the renal plasma flow by PAH clearance before and during an amino acid infusion (Totamine, 6 to 8 mg/kg/min for 90 to 120 min) in 18 transplanted patients with stable renal function. To test the role of the renin-angiotensin system on the renal functional reserve, we performed a crossover placebo-controlled randomized trial of acute blockade of the renin-angiotensin system by injection of perindoprilat (2 mg i.v.), an inhibitor of angiotensin converting enzyme before amino acid infusion, each patient being studied twice at seven day intervals. Amino acid infusion induced a time-dependent increase in the glomerular filtration rate (P = 0.04), whether or not the renin-angiotensin system was blocked. Maximal increases were from 49.1 plusminus 4.1 to 58.9 plusminus 5.4, mean plusminus SE (18.5%), in control conditions and from 52.4 plusminus 5.6 to 62.1 plusminus 5.5 ml/min/1.73 m2 (19.7%) after perindoprilat. The increase in glomerular filtration rate was less pronounced in patients taking cyclosporin A than in patients treated with steroid and azathioprine. Amino acid infusion also induced a significant and time-dependent increase (15.2 to 20.2%) in the renal plasma flow (P < 0.01) whether or not perindoprilat had been given. Furthermore, perindoprilat alone increased renal plasma flow by 13.6%, and this effect seemed additive with that of amino acids. Perindoprilat injection decreased filtration fraction (from 0.20 plusminus 0.01 to 0.19 plusminus 0.01). This parameter returned to basal values after amino acid infusion (0.20 plusminus 0.01). Amino acid infusion decreased renal vascular resistances as did perindoprilat alone. After perindoprilat administration, renal vascular resistances further decreased during amino acid infusion (P = 0.03). These results demonstrate that renal transplant recipients possess a renal functional reserve of which the mobilization is not inhibited in acute experiments by blockade of the renin-angiotensin system.

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References

  1. Brenner BM, Meyer TW, Hostetter TH: Dietary intake and the progressive nature of the kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation and intrinsic renal disease. P Engl J Med 307:652–659, 1982
  2. Bosh JP, Saccaggi A, Lauer A, Rondo C, Belledonne M, Glabman S: Renal functional reserve in humans. Effect of protein intake on glomerular rate. Am J Med 75:943–950, 1983
  3. Hostetter TH: Human renal response to a meat meal. Am J Physiol 250:F613–F618, 1986 | PubMed | ISI | ChemPort |
  4. Rodriguez-Iturbe B, Herrera J, Garcia R: Response to acute protein load in kidney donors and in apparently normal postacute glomerulonephritis patients: Evidence for glomerular hyperfiltration. Lancet 2:461–464, 1985 | PubMed | ChemPort |
  5. Castellino P, Coda B, Defronzo RA: Effect of amino acid infusion on renal hemodynamics in humans. Am J Physiol 251:F132–F140, 1986
  6. Koene RA: The role of adaptation in allograft acceptance. Kidney Int 35:1073–1086, 1989
  7. Anderson S, Meyer TW, Rennke HG, Brenner BM: Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest 76:612–619, 1985 | PubMed | ISI | ChemPort |
  8. Dhaene M, Sabot JP, Philippart Y, Doutrelepont JM, Venherweghem JL: Renal functional reserve of transplanted kidneys. Nephron 44:157–158, 1986
  9. Nunley JR, King A, Comstock T, Posner M, Marshall C, Sica DA: Cyclosporine's effect on functional reserve in the renal allograft. Transplantation 51:190–193, 1991
  10. Greene ER, Avasthi PS: Effect of a high-protein meal on blood flow to transplanted human kidneys. Transplantation 48:584–587, 1989
  11. Bochicchio T, Sandoval G, Ron O, Perez-Grovas H, Bordes J, Herrera-Acosta J: Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives. Kidney Int 38:873–879, 1990 | PubMed | ChemPort |
  12. Meyer TW, Ichikawa I, Zatz R, Brenner BM: The renal hemodynamic response to aminoacid infusion in the rat. Trans Assoc Am Phys 96:76–83, 1983
  13. Woods LL, Mizelle HL, Montani JP, Hall JE: Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids. Am J Physiol 251:F303–F312, 1986
  14. Hirschberg RR, Zipser RD, Slomowitz LA, Kopple JD: Glucagon and prostaglandins are mediators of amino acid-induced rise in renal hemodynamics. Kidney Int 33:1147–1155, 1988 | PubMed |
  15. Premen AJ, Hall JE, Smith MJ Jr: Postprandial regulation of renal hemodynamics: Role of pancreatic glucagon. Am J Physiol 248:F656–F662, 1985
  16. Wada L, Don BR, Schambelan M: Hormonal mediators of amino acid-induced glomerular hyperfiltration in humans. Am J Physiol 260:F787–F792, 1991 | PubMed |
  17. Friedlander G, Blanchet-Benque F, Nitenberg A, Laborie C, Assan R, Amiel C: Glucagon secretion is essential for aminoacid-induced hyperfiltration in man. Nephrol Dial Transplant 5:110–117, 1990
  18. Hirschberg R, Kopple JD: Role of growth hormone in the amino acid-induced acute rise in renal function in man. Kidney Int 32:382–387, 1987
  19. Tolins JP, Raij L: Effects of aminoacid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor. Hypertension 17:1045–1051, 1991
  20. Paller MS, Hostetter TH: Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II. Am J Physiol 251:F34–F39, 1986
  21. Murray BM: Effect of protein intake on regional vascular resistance and reactivity to angiotensin II in the rat. Circ Res 67:440–447, 1990
  22. Ruilope LM, Rodicio J, Garcia Robles R, Sancho J, Miranda B, Granger JP, Romero JC: Influence of a low sodium diet on the renal response to amino acid infusions in humans. Kidney Int 31:992–999, 1987
  23. Corman B, Chami-Khazraji S, Scharverbeke J, Michel JB: Effect of feeding on glomerular filtration rate and proteinuria in conscious aging rats. Am J Physiol 255:F250–F256, 1988 | PubMed |
  24. Laubie M, Schiavi P, Vincent M, Schmitt H: Inhibition of angiotensin I converting enzyme with S-9490: Biochemical effects interspecies differences and role of sodium diet in the hemodynamic effects. J Cardiovasc Pharmacol 6:1076–1082, 1984
  25. Pham Huu Trung MT, Corvol P: A direct determination of plasma aldosterone using a specific aldosterone antibody. Steroids 24:587–598, 1974
  26. Pruszczynski W, Viron B, Czekalski S, Mignon F, Ardaillou R: Role of cardiac parasympathetic dysfunction in atrial natriuretic peptide response to volume changes in patients with chronic renal failure. Miner Electrol Metab 13:333–339, 1987
  27. Liberman J: Elevation of serum angiotensin converting enzyme level in sarcoidosis. Am J Med 59:365–372, 1975
  28. Winer BJ: Statistical Principles in Experimental Design (2nd ed). New York, McGraw-Hill, 1971
  29. Zuccala A, Gaggi R, Zucchelli A, Zucchelli P: Renal functional reserve in patients with a reduced number of functioning glomeruli. Clin Nephrol 32:229–234, 1989 | PubMed |
  30. Bosch JP, Lauer A, Glabmaan S: Short-term protein loading in assessment of patients with renal disease. Am J Med 77:873–879, 1984
  31. Wetzels JEM, Hoitsma AJ, Berden JHM, Koene RAP: Renal hemodynamic effects of a short-term high protein and low protein diet in patients with renal disease. Clin Nephrol 30:42–47, 1988
  32. Cairns HS, Raval U, Neild GH: Failure of cyclosporine A-treated renal allograft recipients to increase glomerular filtration rate following an amino-acid infusion. Transplantation 46:79–82, 1988
  33. Solomon LR, Atherton JC, Bobinski H, Cottam SL, Gray C, Green R, Watts HJ: Effect of a meal containing protein on lithium clearance and plasma immunoreactive atrial natriuretic peptide in man. Clin Sci 75:151–157, 1988
  34. Kanfer A, Dussaule JC, Czekalski S, Rondeau E, Sraer JD, Ardaillou R: Physiological significance of increased levels of endogenous atrial natriuretic factor in human acute renal failure. Clin Nephrol 32:51–56, 1989
  35. Zhang H, Kaseki H, Davis WB, Whisler RL, Cornwell DG: Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysaccharide. Transplantation 47:864–871, 1989
  36. Steinhausen M, Kucherer H, Parekh N, Weis S, Wiegman DL, Wilhelm KR: Angiotensin II control of the renal microcirculation: Effect of blockade by saralasin. Kidney Int 30:56–61, 1986 | PubMed | ISI | ChemPort |
  37. Ter Wee PM, Rosman JB, Van Der Geest S, Sluiter WJ, Donker AJM: Renal haemodynamics during separate and combined infusion of amino-acids and dopamine. Kidney Int 29:870–874, 1986 | PubMed | ChemPort |
  38. Slomowitz LA, Hirschberg R, Kopple JD: Captopril augments the renal response to an amino acid infusion in diabetic adults. Am J Physiol 255:F755–F762, 1988 | PubMed | ChemPort |
  39. Rosenberg ME, Chmielewski D, Hostetter TH: Effect of dietary protein on rat renin and angiotensinogen gene expression. J Clin Invest 85:1144–1149, 1990 | PubMed | ISI | ChemPort |

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