Abstract
Although the prevalence of nephrotoxicity in patients treated with nonsteroidal anti-inflammatory
drugs (NSAIDs) is relatively low, the extensive use profile of these agents implies
that many persons are at risk. At basal states of normal renal function, the role
of renal prostaglandin production for maintenance of stable renal hemodynamic function
is relatively limited. Nonetheless, in the clinical setting of reduced renal perfusion
as seen in various forms of cardio-renal disease, dehydration, and the aging kidney,
the adequacy of renal prostaglandin production mediated predominantly by cyclooxygenase-1
(COX-1) and, potentially, by COX-2 enzyme activity becomes of major significance in
the activation of compensatory renal hemodynamics. Inhibition of renal prostaglandin
production by the use of NSAIDs in these circumstances can potentially lead to the
emergence of several distinct syndromes of disturbed renal function. These include
fluid and electrolyte disorders, acute renal dysfunction, nephrotic syndrome/interstitial
nephritis, and renal papillary necrosis. In addition, by blunting the homeostatic
renal effects of prostaglandins, NSAIDs can adversely influence blood pressure control,
particularly during the use of angiotensin-converting enzyme (ACE) inhibitors, diuretics,
and β blockers. This is a matter of considerable public health concern, in that some
12 million US citizens are concurrently treated with NSAIDs and antihypertensive drugs.
Finally, the risk of congestive heart failure is significantly increased when NSAIDs
are given to patients receiving diuretic therapy who have cardiovascular risk factors.
Physiologic factors, clinical presentations, diagnostic modalities, and clinical management
strategies appropriate to these NSAID-induced renal syndromes are described.
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References
Whelton A, Watson J. Nonsteroidal anti-inflammatory drugs: effects on kidney function. In: De Broe ME, Porter GA, Bennett WM, Verpooten GA, eds. Clinical Nephrotoxins: Renal Injury From Drugs and Chemicals. Dordrecht, Netherlands: Kluwer Academic Publishers, 1997:209–222.
- Nonsteroidal antiinflammatory drugs.J Clin Pharmacol. 1991; 31: 588-598
- Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure.Ann Intern Med. 1990; 112: 568-576
- Nonsteroidal antiinflammatory drugs.West J Med. 1991; 155: 39-42
Oates JA, FitzGerald GA, Branch RA, et al. Clinicalimplications of prostaglandin and thromboxane A2 formation. N Engl J Med. 1988;319:689–698, 761–767.
- Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle.J Clin Invest. 1979; 64: 495-502
- Inhibition of sodium transport by prostaglandin E2 across the isolated perfused rabbit collecting tubule.J Clin Invest. 1977; 59: 1099-1104
- Effect of prostaglandin (PGE1) on the permeability response of the toad bladder to vasopressin, theophylline, and adenosine 3′,5′-monophosphate.Nature. 1985; 205: 397-398
- Evidence for an in vivo antagonism between vasopressin and prostaglandin in the mammalian kidney.J Clin Invest. 1975; 56: 420-426
- Therapeutic implications associated with renal studies of nabumetone.J Rheumatol. 1992; 19: 25-31
- Nonsteroidal antiinflammatory drugs.Clin Geriatr Med. 1990; 6: 365-397
- Edema associated with ibuprofen therapy.JAMA. 1977; 237: 1716-1717
- Ibuprofen-induced hyponatremia.Rheumatol Rehab. 1980; 19: 258-259
- Renal syndromes associated with nonsteroidal anti-inflammatory drugs.N Engl J Med. 1984; 310: 563-572
Whelton A. Nonsteroidal anti-inflammatory drugs: effects on kidney function. In: Greenberg A, ed. Primer on Kidney Diseases. San Diego, CA: Academic Press, 1994:163–167.
- Severe hyperkalemia caused by indomethacin and potassium supplementation.South Med J. 1985; 78: 756-757
- Indomethacin- and Moduretic-induced hyperkalemia.Isr J Med Sci. 1983; 19: 535-537
- Reversible acute renal insufficiency and hyperkalemia following indomethacin therapy.JAMA. 1981; 246: 154-155
- Indomethacin-induced azotemia and hyperkalemia.N Z Med J. 1981; 94: 377-379
- Indomethacin-induced hyperkalemia in 3 patients with gouty arthritis.JAMA. 1980; 244: 1127-1128
- Indomethacin-induced hyperkalemia and renal failure in multiple myeloma.Acta Haematol (Basel). 1982; 68: 256-260
- Indomethacin-induced prostaglandin inhibition with hyperkalemia.Ann Intern Med. 1979; 90: 783-785
- Acute oliguric renal failure induced by indomethacin.Ann Intern Med. 1979; 91: 47-49
- The effect of indomethacin on proteinuria and kidney function in the nephrotic syndrome.Acta Med Scand. 1976; 199: 121-125
- Irreversible renal failure after indomethacin in steroid-resistant nephrosis.N Engl J Med. 1980; 302: 691
- Renal complications of nonsteroidal anti-inflammatory drugs.Semin Arthritis Rheum. 1985; 14: 163-175
- Reversible acute renal failure from combined triamterene and indomethacin.Ann Intern Med. 1982; 96: 317-320
- Acute intrinsic renal failure induced by indomethacin.Mayo Clin Proc. 1982; 57: 289-296
- Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure.Ann Intern Med. 1990; 112: 568-576
- Effects of ibuprofen, naproxen, and sulindac on prostaglandins in men.Kidney Int. 1985; 27: 66-73
- Effects of sulindac and indomethacin on renal prostaglandin synthesis.Clin Pharmacol Ther. 1984; 36: 85-91
- Effects of sulindac and ibuprofen in patients with chronic glomerular disease.N Engl J Med. 1984; 310: 279-283
- Sulindac.JAMA. 1982; 248: 2864-2867
- Sulindac reduces the urinary excretion of prostaglandins and impairs renal function in patients with cirrhosis and ascites.Nephron. 1986; 42: 298-303
- Glomerular and interstitial disease induced by nonsteroidal anti-inflammatory drugs.Am J Nephrol. 1984; 4: 1-6
- Patterns of tubulo-interstitial damage associated with nonsteroidal anti-inflammatory drugs.Semin Nephrol. 1988; 8: 55-61
- Interstitial nephritis, proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs.Am J Med. 1984; 76: 1006-1012
- T and B lymphocyte subsets in fenoprofen nephropathy.Am J Med. 1983; 75: 9-16
- Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs.JAMA. 1996; 276: 466-469
- Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.JAMA. 1979; 242: 1896-1898
- Mefenamic acid nephropathy.Lancet. 1980; 2: 232-233
- Renal papillary necrosis due to ibuprofen.Arthritis Rheum. 1981; 24: 1208-1210
- Papillary necrosis following phenylbutazone ingestion.Arch Surg. 1971; 103: 420-421
- The renal circulation.JAMA. 1978; 239: 1308-1312
- Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis.Am J Med. 1974; 227: 801-805
- Epidemiology and mechanistic basis of analgesic-associated nephropathy.Toxicol Lett. 1989; 46: 141-151
- Effects of non-narcotic analgesics on the kidney.Drugs. 1986; 32: 108-128
- Renal medullary necrosis.Am J Med. 1960; 29: 132
- Unilateral renal papillary necrosis.J Urol. 1955; 73: 757
- Acute renal papillary necrosis induced by ibuprofen.Am J Therapeut. 1997; 4: 55-60
- Recovery of papillae in renal papillary necrosis.Arch Pathol. 1963; 75: 501
- On renal papillary necrosis with special reference to the diagnostic importance of papillary fragments in the urine, therapy, and prognosis.Acta Med Scand. 1960; 167: 319
- Radiological changes of renal papillary necrosis.Kidney Int. 1978; 13: 93
- Renal papillary necrosis.Acta Radiol (Stockholm). 1960; 192: 1
Buckalew VM Jr. Analgesic abuse nephropathy. In: Greenberg A, ed. Primer on Kidney Disease. San Diego, CA: Academic Press, 1994:192–196.
- Carcinoma of the renal pelvis in renal papillary necrosis.Acta Chir Scand. 1965; 130: 314-320
- Malignancies of the urinary tract and their relation to analgesic abuse.Kidney Int. 1978; 13: 107-113
- Analgesics and cancer of the pelvis in New South Wales.Cancer. 1982; 49: 2617-2625
- A safety assessment of fixed combinations of acetaminophen and acetylsalicylic acid, coformulated with caffeine.Renal Failure. 1998; 20: 749-762
- Blood pressure, stroke, and coronary heart disease: part 2. Short-term reductions in blood pressure: prospective observational studies corrected for the regression dilution bias.Lancet. 1990; 335: 827-838
Ruoff GE. The impact of nonsteroidal anti-inflammatory drugs on hypertension: alternative analgesics for patients at risk. Clin Ther. 2998;20:376–387.
- Detection and treatment of hypertension in elderly individuals.Am J Epidemiol. 1985; 121: 371-376
- Non-steroidal anti-inflammatory drugs and hypertension in the elderly.Br J Clin Pharmacol. 1993; 35: 455-459
- Nonsteroidal anti-inflammatory drugs and antihypertensives.Am J Med. 1991; 90: 42-47
- A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure.Arch Intern Med. 1993; 153: 477-484
- Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis.Ann Intern Med. 1994; 21: 289-300
- Diuretic therapy.N Engl J Med. 1998; 339: 387-395
- Pharmacokinetic and -dynamic analysis of the indomethacin–furosemide interaction in man.J Pharmacol Exp Ther. 1980; 215: 77-81
- Nephron site of effect of nonsteroidal anti-inflammatory drugs on solute excretion in humans.Am J Physiol. 1983; 244: F134-F139
- NSAIDs and increased blood pressure.Drug Safety. 1997; 17: 277-289
- Nonsteroidal anti-inflammatory drugs and antihypertensives.Nephron. 1990; 56: 345-352
- The mechanism of bradykinin potentiation after inhibition of angiotensin-converting enzyme by SQ 14,225 in conscious rabbits.Circ Res. 1978; 43: 40-45
- Acute renal excretory actions of losartan in spontaneously hypertensive rats.J Hypertens. 1995; 13: 1779-1784
- Prostaglandin synthesis by vascular smooth muscle cells is stimulated by bradykinin, prazosin, and hydralazine.Prog Lipid Res. 1981; 20: 557-560
- Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy.JAMA. 1994; 272: 781-786
- NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics.Arch Intern Med. 1998; 158: 1108-1112
- Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction.J Clin Invest. 1994; 94: 2504-2510
- In vivo and in vitro osmotic regulation of HSP-70 and prostaglandin synthase gene expression in kidney cells.Am J Physiol. 1995; 269: F854-F862
- Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse.Cell. 1995; 83: 473-482
- Interspecies differences in renal localization of cyclooxygenase isoforms.Toxicol Pathol. 1998; 26: 612-620
Gresham AK, Venturini CM, Edwards D, Ornberg RL. COX-2 expression is induced in the macula densa in volume depleted dogs. FASEB J. 1997;11:A-461.
- Upregulation of renal and systemic cyclooxygenase 2 in patients with active lupus nephritis.J Am Soc Nephrol. 1998; 9: 1202-1212
- Localization of cyclooxygenase-1 and 2 in adult and fetal human kidney.Am J Physiol. 1997; 272: F460-F468
Article Info
Publication History
Published online: August 16, 2004
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© 1999 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
