Angiotensin-converting enzyme inhibitors (ACE-I) have a renoprotective effect in patients with chronic renal failure. Prostaglandins (PGs) have also been shown to ameliorate renal impairment. Although these two have different mechanisms—ACE-I reduces intraglomerular pressure by dilating the efferent arterioles, while it is thought that PGs may increase intraglomerular pressure—coadministration of these drugs may have an additive effect. Administration of a PG with an ACE-I might have an additive effect on chronic renal failure. However, there have been no studies on the efficacy of such a combination therapy. This study was conducted to determine whether combination therapy with PGE1 and an ACE-I might have a long-term benefit on chronic renal failure. Sixty patients with chronic renal disease receiving an ACE-I in advance were assigned to receive an ACE-I alone or an ACE-I plus PGE1. Blood pressure, blood chemistry, urinary protein excretion, and the changes in the reciprocal of serum creatinine (Δ1/Cr) were monitored once monthly for an average of 36.5 months. In patients treated only with an ACE-I, the progression of renal failure did not change with time. In contrast, the decline of renal function was significantly reduced with the combination therapy. The renoprotective effect of the combination therapy was not exerted by reduced proteinuria or by decreased blood pressure. PGE1 may reinforce the renoprotective effects of ACE-I to prevent the progression of chronic renal failure.
The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) : Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–1863.
Klahr S, Levey AS, Beck GJ, et al: The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N Engl J Med 1994; 330: 877–884.
Torsello G, Schror K, Szabo Z, et al: Effects of prostaglandin E1 (PGE1) on experimental renal ischaemia. Eur J Vasc Surg 1989; 3: 5–13.
Nagao T, Nagamatsu T, Suzuki Y : Effect of lipo-prostaglandin E1 on crescentic-type anti-glomerular basement membrane nephritis in rats. Eur J Pharmacol 1998; 348: 37–44.
Yoshikawa T, Suzuki H, Kato H, Yano S : Effects of prostaglandin E1 on collagen diseases with high levels of circulating immune complexes. J Rheumatol 1990; 17: 1513–1514.
Lin CY : Improvement in steroid and immunosuppressive drug resistant lupus nephritis by intravenous prostaglandin E1 therapy. Nephron 1990; 55: 258–264.
Okada S, Ogino Y, Ichiki K, et al: Effect of prostaglandin E1 on renal haemodynamics in a patient with diabetic nephropathy. J Int Med Res 1991; 19: 497–500.
Koch JA, Plum J, Grabensee B, Modder U, PGE1 Study Group : Prostaglandin E1: a new agent for the prevention of renal dysfunction in high risk patients caused by radiocontrast media? Nephrol Dial Transplant 2000; 15: 43–49.
Abe K, Fujino Y, Sakakibara T : The effect of prostaglandin E1 during cardiopulmonary bypass on renal function after cardiac surgery. Eur J Clin Pharmacol 1993; 45: 217–220.
Moran M, Mozes MF, Maddux MS, et al: Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cyclosporine and prednisone. N Engl J Med 1990; 322: 1183–1188.
Niwa T, Maeda K, Naotsuka Y, et al: Improvement of renal function with prostaglandin E1 infusion in patients with chronic renal disease. Lancet 1982; 1: 687.
Fernandez-Llama P, Poch E, Oriola J, et al: Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis. Kidney Int 1998; 53: 1743–1747.
Yu H, Zhang Y, Liu G : Relationship between polymorphism of the angiotensin-converting enzyme gene and the response to angiotensin-converting enzyme inhibition in hypertensive patients. Hypertens Res 2003; 26: 881–886.
Lianos EA : Biosynthesis and role of arachidonic acid metabolites in glomerulonephritis. Nephron 1984; 37: 73–77.
Levenson DJ, Simmons CE Jr, Brenner BM : Arachidonic acid metabolism, prostaglandins and the kidney. Am J Med 1982; 72: 354–374.
Brenner BM : Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 1983; 23: 647–655.
Utsunomiya Y, Ogura M, Kawamura T, Mitarai T, Maruyama N, Sakai O : Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue. Clin Exp Immunol 1995; 99: 454–460.
Sakai A, Yajima M, Nishio S : Cytoprotective effect of TRK-100, a prostacyclin analogue, against chemical injuries in cultured human vascular endothelial cells. Life Sci 1990; 47: 711–719.
Gerber JG, Keller RT, Nies AS : Prostaglandins and renin release: the effect of PGI2, PGE2, and 13,14-dihydro PGE2 on the baroreceptor mechanism of renin release in the dog. Circ Res 1979; 44: 796–799.
Ito S, Carretero OA, Abe K, Beierwaltes WH, Yoshinaga K : Effect of prostanoids on renin release from rabbit afferent arterioles with and without macula densa. Kidney Int 1989; 35: 1138–1144.
Okuda T, Kojima I, Ogata E, Kurokawa K : Ambient C1- ions modify rat mesangial cell contraction by modulating cell inositol trisphosphate and Ca2+ via enhanced prostaglandin E2. J Clin Invest 1989; 84: 1866–1872.
Kanazawa M, Kohzuki M, Yoshida K, et al: Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist: beyond the renoprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation. Hypertens Res 2002; 25: 447–453.
Kanazawa M, Kohzuki M, Kurosawa H, et al: Renoprotective effect of angiotensin-converting enzyme inhibitor combined with alpha1-adrenergic antagonist in spontaneously hypertensive rats with renal ablation. Hypertens Res 2004; 27: 509–515.
Perinotto P, Biggi A, Carra N, et al: Angiotensin II and prostaglandin interactions on systemic and renal effects of L-NAME in humans. J Am Soc Nephrol 2001; 12: 1706–1712.
Iino Y, Hayashi M, Kawamura T, et al: Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension—a report of the Japanese Losartan Therapy Intended for the Global Renal Protection in Hypertensive Patients (JLIGHT) study. Hypertens Res 2004; 27: 21–30.
About this article
Cite this article
Nakayama, Y., Nonoguchi, H., Kiyama, S. et al. Long-Term Renoprotective Effect of Combination Therapy with Prostaglandin E1 and Angiotensin-Converting Enzyme Inhibitor in Patients with Chronic Renal Failure. Hypertens Res 28, 733–739 (2005). https://doi.org/10.1291/hypres.28.733
- chronic renal failure
- angiotensin-converting enzyme inhibitor
Low-dose but not high-dose prostaglandin E1 improves the histological outcome of severe forebrain ischemia in rats
Journal of Anesthesia (2010)