Your activity: 246 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

NSAIDs: Acute kidney injury

NSAIDs: Acute kidney injury
Authors:
Randy Luciano, MD, PhD
Mark A Perazella, MD, FACP
Section Editor:
Paul M Palevsky, MD
Deputy Editor:
Eric N Taylor, MD, MSc, FASN
Literature review current through: Dec 2022. | This topic last updated: Nov 18, 2021.

INTRODUCTION — Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications used for analgesic and antiinflammatory benefits. NSAIDs can induce several different forms of kidney injury including hemodynamically mediated acute kidney injury (AKI); electrolyte and acid-base disorders; acute interstitial nephritis (AIN), which may be accompanied by the nephrotic syndrome; and papillary necrosis (table 1).

This topic reviews hemodynamically mediated AKI. The roles of NSAIDs in AIN, chronic kidney disease (CKD), and electrolyte disorders are discussed elsewhere:

(See "Clinical manifestations and diagnosis of acute interstitial nephritis".)

(See "Epidemiology and pathogenesis of analgesic-related chronic kidney disease".)

(See "NSAIDs: Electrolyte complications".)

The mechanism of action, therapeutic action, and non-kidney-related adverse effects of NSAIDs are also discussed elsewhere:

(See "NSAIDs: Pharmacology and mechanism of action".)

(See "NSAIDs: Therapeutic use and variability of response in adults".)

(See "Nonselective NSAIDs: Overview of adverse effects".)

(See "NSAIDs: Adverse cardiovascular effects".)

EPIDEMIOLOGY — Adverse kidney events occur in approximately 1 to 5 percent of all patients using nonsteroidal antiinflammatory drugs (NSAIDs) [1]. Because of the large number of patients that take NSAIDs (estimates of more than 70 million prescriptions and 30 billion over-the-counter doses annually), this translates to upwards of 2.5 million patients experiencing a nephrotoxic event annually [2].

Use of NSAIDs increases the risk of AKI by nearly twofold [3], and the risk diminishes after cessation of the drug [4].AKI can occur with any class of traditional, nonselective NSAID or cyclooxygenase-2 (COX-2)-specific NSAIDs [5-10]. As an example, in a nested, case-control study that included 121,722 older patients, an increased risk of hospitalization within 30 days was associated with initiation of nonselective NSAIDs (other than naproxen), naproxen, rofecoxib, and celecoxib with relative risks (RRs) of 2.3, 2.4, 2.3, and 1.5, respectively, compared with unexposed individuals [10].

The selective COX-2 inhibitors also decrease glomerular filtration rate (GFR) [8-13]. In a randomized, controlled study, indomethacin and rofecoxib decreased GFR (as measured by inulin or iothalamate clearance) to a similar degree among older patients [14]. Case reports and case series also show that the selective COX-2 inhibitors have a nephrotoxicity profile similar to traditional NSAIDs, causing AKI, edema, and electrolyte disorders [9].

RISK FACTORS — Risk factors for nonsteroidal antiinflammatory drug (NSAID)-induced AKI include chronic kidney disease (CKD); volume depletion from aggressive diuresis, vomiting or diarrhea, or effective arterial volume depletion due to heart failure, nephrotic syndrome, or cirrhosis; and severe hypercalcemia (figure 1). Certain medications, including diuretics, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and calcineurin inhibitors (CNIs), may increase the risk of NSAID-induced AKI.

Among older patients with CKD, NSAID users are more likely to have deterioration of kidney function over time compared with patients who do not use NSAIDs chronically, and higher doses of NSAIDs are associated with a greater risk of a decline in kidney function [15]. It is not known whether the decline in kidney function among such patients is related to episodes of AKI, however. (See "Epidemiology and pathogenesis of analgesic-related chronic kidney disease".)

An observational study reported an increase in mean estimated glomerular filtration rate (eGFR) among 1522 patients who had NSAIDs discontinued [16]. This study analyzed NSAID prescribing patterns and eGFR among 1522 patients with CKD stage 3, 4, and 5 before and after implementation of mandatory reporting of eGFR to clinicians. A 10.2 percent reduction in NSAID prescriptions followed reporting of eGFR. The mean eGFR increased from 45.9 to 46.9, 23.9 to 27.1, and 12.4 to 26.4 mL/min/1.73 m2 among patients with eGFRs of 30 to 59, 15 to 29, and <15 mL/min/1.73 m2, respectively, after reporting of the eGFR.

Patients with effective arterial volume depletion due to a condition such as heart failure are also at higher risk for NSAID-induced AKI. In a nested, case-controlled study of 386,916 patients, those who used NSAIDs and had heart failure had a higher risk of AKI compared with those who used NSAIDs but did not have heart failure and with those who did not use NSAIDs (relative risks [RRs] of 7.63, 3.34, and 2.82, respectively) [17].

Diuretics, ACE inhibitors, or ARBs may increase the risk of NSAID-induced hemodynamically mediated AKI. This was suggested in a nested, case-control cohort study in which the concomitant use of such medications was associated with an increased rate of AKI (odds ratio [OR] 1.31, 95% CI 1.12-1.53), with the highest risk within the first 30 days of therapy (OR 1.82, 95% CI 1.35-2.46) [18]. The use of NSAIDS, diuretics, ACE inhibitors, or ARBs alone did not result in significant AKI.

The risk for AKI is also elevated when NSAIDs are combined with maintenance CNI therapy in recipients of solid organ or hematopoietic cell transplants [19]. AKI occurred in 5 of 41 patients exposed to CNIs and NSAIDs compared with 7 of 126 transplant recipients only given CNIs (12 versus 6 percent). An increase in serum creatinine above baseline was also more frequent among patients exposed to both CNIs and NSAIDs (80 versus 56 percent).

KIDNEY PROSTAGLANDIN EXPRESSION AND FUNCTION — Prostaglandins (PGs) are lipids synthesized from cell membrane phospholipids (figure 2). Through the enzymatic activity of phospholipase A2, lipids are converted to arachidonic acid (AA), which is converted to a PG or leukotriene precursor in the presence of cyclooxygenase (COX) or lipoxygenase enzymes, respectively. The enzymes responsible for conversion of AA to PG precursors are COX-1 and COX-2. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the activity of both COX-1 and COX-2 enzymes (although there is enzyme-specific preference amongst traditional NSAIDS and there are specific COX-2 inhibitors). There are five PGs (PGD2, PGE2, PGF2, PGI2, and thromboxane A2) that are synthesized from a common precursor by PG-specific synthases.

In the kidney, COXs are locally produced at many sites, including glomerular and vascular endothelium, the medullary and cortical collecting tubules, and medullary interstitial cells. COX-1 is expressed ubiquitously in most tissues, while COX-2 expression is low at basal levels but increases with stimulation in the setting of acute or chronic inflammation [20] and other physiologic challenges. The tubules predominantly synthesize PGE2, while the glomeruli synthesize both PGE2 and PGI2 [21].

Kidney PGs are primarily vasodilators in the kidneys. Under basal conditions, PGs have no significant role in the regulation of kidney perfusion. However, in the setting of hypotension and reduced kidney perfusion from vasoconstriction stimulated by angiotensin II, norepinephrine, vasopressin, or endothelin, PG synthesis is increased to maintain kidney perfusion and minimize ischemia [22-25].

In addition to modulating renal hemodynamics, PGs also increase renin secretion [26,27], antagonize the water-retentive effects of arginine vasopressin [25,28], and enhance sodium excretion [29,30].

MECHANISM OF ACUTE KIDNEY INJURY — Nonsteroidal antiinflammatory drug (NSAID) inhibition of cyclooxygenase (COX) enzymes with subsequent reduction in prostaglandin (PG) synthesis can lead to reversible kidney ischemia, a decline in glomerular hydraulic pressure (the major driving force for glomerular filtration), and AKI [6,7,17].

This occurs via an NSAID-induced attenuation of renal vasodilation. In healthy patients, PGs play little role in renal hemodynamics. However, PG synthesis is increased in the setting of prolonged renal vasoconstriction, which serves to protect the glomerular filtration rate (GFR). PG synthesis is increased in the following conditions (table 2) [6,7,31]:

Chronic kidney disease (CKD), especially stage 3 or worse (ie, estimated GFR [eGFR] <60 mL/min/1.73 m2)

Volume depletion from aggressive diuresis, vomiting, or diarrhea

Effective arterial volume depletion due to heart failure, nephrotic syndrome, or cirrhosis

Older age

Severe hypercalcemia with associated renal arteriolar vasoconstriction

In these settings, PGs act to preserve renal blood flow and GFR by decreasing preglomerular resistance (figure 3). This differs from PG function in the setting of glomerular disease, where increased PG production maintains GFR in the presence of a significant reduction in glomerular capillary permeability [32].

NSAID-induced inhibition of PG-mediated afferent vasodilation and reduction in peritubular blood flow may also increase the risk of ischemic acute tubular necrosis (ATN) or other nephrotoxin-induced tubular injury from drugs such as aminoglycosides, amphotericin B, hydroxyethyl starch, and radiocontrast material [33,34]. As an example, a retrospective study showed that, among 38 patients without heart failure who developed contrast-associated AKI, 8 percent were prescribed NSAIDs prior to contrast exposure [35].

PREVENTION — Nonsteroidal antiinflammatory drug (NSAID)-induced hemodynamically mediated AKI may be prevented by avoiding NSAIDs among high-risk patients (such as those with advanced chronic kidney disease [CKD], volume depletion, heart failure, or hypercalcemia). (See 'Risk factors' above.)

NSAID use should be limited among patients at high risk for NSAID-induced AKI, including those with reduced estimated glomerular filtration rate (eGFR), volume depletion, heart failure, nephrotic syndrome, cirrhosis, and hypercalcemia.

We suggest that the chronic use of NSAIDs be avoided, if at all possible, among all patients with an eGFR <30 mL/min/1.73 m2 and suggest cautious use in patients with an eGFR 30 to 89 mL/min/1.73 m2 and other comorbid conditions or risk factors, including heart failure, cirrhosis, or nephrotic syndrome. NSAIDs should never be used in patients with stage 5 CKD unless the primary goal is comfort and palliation.

In patients with stages 1 to 3 CKD in whom predisposing nephrotoxic risk factors are adequately addressed, short-acting NSAIDs used for up to seven days is a reasonable pain management strategy with an acceptably low risk of serious AKI. Routine laboratory tests and follow-up within two to three weeks should be undertaken to monitor for nephrotoxicity. Long-term therapy may be employed in patients cognizant of those conditions (vomiting, diarrhea, volume depletion, etc) that should prompt immediate NSAID discontinuation [36].

Even the episodic use of NSAIDs may confer a risk of AKI among patients with reduced eGFR (stage 4 and 5 CKD), and no "safe" dose or duration of NSAID has been defined. For patients with reduced eGFR (15 to 30 mL/min/1.73 m2) in whom limited NSAID use is unavoidable (such as those with significant pain or mobility issues in whom other pain medications are significantly less effective), short half-life NSAIDs used for ≤5 days may be employed as long as the patient is advised of the risk and the serum creatinine is followed closely during therapy [36]. In patients with CKD, opioids may be associated with more adverse effects than NSAIDs [37].

Despite efforts to minimize use in at-risk patients, many patients with CKD continue to use NSAIDs. In a cross-sectional study of 12,065 adults, chronic NSAID use (as defined as nearly every day for 30 days or longer) was reported among 5 percent of patients with moderate to severe CKD (eGFR of 15 to 59 mL/min/1.73 m2) [38]. Awareness of having CKD did not appear to alter NSAID use in this study.

Clinicians and patients also need to be aware of medications that may increase the risk of hemodynamically mediated AKI when used concomitantly with NSAIDs. (See 'Risk factors' above.)

Patients should not receive NSAIDs prior to procedures involving radiocontrast or other nephrotoxic drug administration. In a study cited above, a large number of patients who developed contrast-associated AKI had been taking NSAIDs prior to contrast exposure [35]. (See 'Mechanism of acute kidney injury' above.)

CLINICAL MANIFESTATIONS — Patients generally present with an increase in the plasma creatinine that is usually detected incidentally during an evaluation of an unrelated problem. The increase in the plasma creatinine concentration usually occurs within the first three to seven days of therapy, which is the time required for attainment of steady-state drug levels and therefore maximum inhibition of prostaglandin synthesis [39]. However, the increase in plasma creatinine may occur at any point.

Urinalysis is usually negative for hematuria and proteinuria. Although low-level proteinuria (<500 mg/day) may be observed, significant proteinuria (ie, >1 g/day) is uncommon and suggests a nonsteroidal antiinflammatory drug (NSAID)-induced glomerular lesion (minimal change disease or membranous nephropathy) rather than hemodynamically mediated AKI.

The urine sediment may contain hyaline casts and, if acute tubular necrosis (ATN) has developed, renal tubular epithelial cell casts, renal tubular epithelial cells, or granular casts. White blood cells (WBCs) and WBC casts are not seen in hemodynamically mediated AKI and suggest acute interstitial nephritis (AIN). (See 'Differential diagnosis' below.)

DIAGNOSIS — The diagnosis of hemodynamically mediated AKI associated with nonsteroidal antiinflammatory drugs (NSAIDs) is similar to other forms of AKI (see "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of kidney disease'). The diagnosis is suggested by the history of recent NSAID use, the absence of significant proteinuria (<500 mg/day), and hematuria and the bland urine sediment.

Among all patients with AKI, we generally obtain a kidney ultrasound to exclude possible urinary tract obstruction. If the history is overwhelmingly consistent with NSAID initiation or subacute or chronic use, we avoid other costly tests as generally the diagnosis is made when recovery of kidney function occurs after the NSAID is discontinued. The time course to recovery can be dependent on underlying kidney disease and any additional confounding kidney injury (such as acute tubular necrosis [ATN]). If injury is truly hemodynamic in nature and due to NSAID use, recovery should begin within 24 to 72 hours. Failure to recover or progression despite removal of NSAIDs should warrant a biopsy within three to seven days, depending on the clinical course. A biopsy may also be done in patients who have features of acute interstitial nephritis (AIN) or a glomerular lesion, such as nephrotic-range proteinuria, hematuria with dysmorphic red blood cells, and/or red blood cell casts.

Differential diagnosis — The differential diagnosis of AKI is broad and is discussed elsewhere (see "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting", section on 'Major causes and pathogenesis of kidney disease'). Among patients who present with an increased plasma creatinine in the setting of NSAID use, other NSAID-associated lesions, such as AIN, or an NSAID-related glomerular lesion are among the differential diagnoses. It is important to establish the chronicity of NSAID use and the duration of the increased plasma creatinine, if possible. This is necessary to distinguish between AKI and the more subacute to chronic AIN, which may occur with or without features of nephrotic syndrome.

The urinalysis and quantitation of proteinuria may distinguish between hemodynamically mediated AKI and AIN. Whereas the urine sediment is generally bland among patients with hemodynamically mediated AKI, urine white blood cells (WBCs) and WBC casts are often observed among patients with AIN. (See 'Clinical manifestations' above.)

Quantitation of urine protein excretion may differentiate between hemodynamically mediated AKI and an NSAID-induced glomerular lesion such as membranous nephropathy or minimal change disease. As noted above, proteinuria is absent or modest among patients with hemodynamically mediated AKI and generally >1 g/day among patients with a glomerular lesion.

The urinalysis will also identify patients who have ATN. Among patients with ATN, the sediment may contain renal tubular epithelial cells, renal tubular epithelial cell casts, or muddy brown granular casts.

TREATMENT — Treatment of nonsteroidal antiinflammatory drug (NSAID)-associated hemodynamically mediated AKI is no different than other forms of AKI. The offending agent needs to be stopped immediately. Volume resuscitation should be provided in states of hypovolemia and continued based on reassessment of volume status including blood pressure/pulse, urine output, and other parameters. Kidney replacement therapy is rarely required but may be needed initially when severe AKI has occurred and there are serious electrolyte and acid-base disturbances present.

CHRONIC KIDNEY DISEASE — In addition to hemodynamically mediated AKI, it has been proposed that daily nonsteroidal antiinflammatory drug (NSAID) use for a prolonged period of time may be associated with an increased risk of chronic kidney disease (CKD), perhaps due to papillary necrosis or chronic interstitial nephritis similar to that seen with other analgesics. This issue is discussed separately. (See "Epidemiology and pathogenesis of analgesic-related chronic kidney disease".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute kidney injury in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Acute kidney injury (The Basics)" and "Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (The Basics)")

SUMMARY AND RECOMMENDATIONS

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications used for analgesic and antiinflammatory benefits. NSAIDs can induce several different forms of kidney injury including hemodynamically mediated acute kidney injury (AKI); electrolyte and acid-base disorders and acute interstitial nephritis (AIN), which may be accompanied by the nephrotic syndrome; and papillary necrosis. (See 'Introduction' above.)

All nonselective NSAIDs or cyclooxygenase (COX)-2-specific NSAIDs may cause AKI via the attenuation of renal vasodilation. Risk factors for NSAID-induced AKI include chronic kidney disease (CKD); volume depletion from aggressive diuresis, vomiting or diarrhea, or effective arterial volume depletion due to heart failure, nephrotic syndrome, or cirrhosis; and severe hypercalcemia. Medications including diuretics, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and calcineurin inhibitors (CNIs) may increase the risk of NSAID-induced AKI. Higher doses of NSAIDs are associated with a greater risk of AKI. (See 'Risk factors' above and 'Mechanism of acute kidney injury' above.)

NSAID-induced AKI may be prevented by avoiding NSAIDs among high-risk patients. NSAID use should be limited among patients with reduced estimated glomerular filtration rate (eGFR), volume depletion, heart failure, nephrotic syndrome, cirrhosis, and hypercalcemia. The chronic use of NSAIDs should be avoided, if at all possible, among patients with an eGFR <30 mL/min/1.73 m2 and used cautiously in those with an eGFR 30 to 89 mL/min/1.73 m2. NSAIDs should never be employed in patients with stage 5 CKD unless the primary goal is comfort and palliation. For patients with reduced eGFR (15 to 30 mL/min/1.73 m2) in whom limited NSAID use is unavoidable (such as those with significant pain or mobility issues in whom other pain medications are significantly less effective), the patient should be advised of the risk, and the plasma creatinine should be followed closely when receiving NSAIDs. (See 'Prevention' above.)

Patients generally present with an incidentally detected increase in the plasma creatinine. Urinalysis is usually negative for hematuria and proteinuria. The urine sediment may contain hyaline casts and, if acute tubular necrosis (ATN) has developed, renal tubular epithelial cell casts, renal tubular epithelial cells, or granular casts. White blood cells (WBCs) and WBC casts are not seen in hemodynamically mediated AKI and suggest acute interstitial nephritis (AIN). (See 'Diagnosis' above.)

Among all patients with AKI, we generally obtain a kidney ultrasound to exclude possible urinary tract obstruction. If the history is overwhelmingly consistent with NSAID initiation or subacute or chronic use, we avoid other costly tests as generally the diagnosis is made when recovery of kidney function occurs after the NSAID is discontinued. Failure to recover within three to seven days or progression despite removal of NSAIDs should warrant a biopsy. A kidney biopsy may also be done in patients who have features of AIN or a glomerular lesion, such as nephrotic-range proteinuria or hematuria with dysmorphic red blood cells or red blood cell casts. (See 'Diagnosis' above.)

Treatment of NSAID-induced AKI is similar to that of other forms of AKI. The NSAID should be stopped immediately. Volume resuscitation should be provided in states of hypovolemia and continued based on reassessment of volume status including blood pressure/pulse, urine output, and other parameters. Kidney replacement therapy is rarely required but may be needed initially when severe AKI has occurred and there are serious electrolyte and acid-base disturbances present. (See 'Treatment' above.)

  1. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 1999; 106:13S.
  2. Green GA. Understanding NSAIDs: from aspirin to COX-2. Clin Cornerstone 2001; 3:50.
  3. Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol 2017; 18:256.
  4. Chou CI, Shih CJ, Chen YT, et al. Adverse Effects of Oral Nonselective and cyclooxygenase-2-Selective NSAIDs on Hospitalization for Acute Kidney Injury: A Nested Case-Control Cohort Study. Medicine (Baltimore) 2016; 95:e2645.
  5. Haragsim L, Dalal R, Bagga H, Bastani B. Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Am J Kidney Dis 1994; 24:578.
  6. Oates JA, FitzGerald GA, Branch RA, et al. Clinical implications of prostaglandin and thromboxane A2 formation (1). N Engl J Med 1988; 319:689.
  7. Patrono C, Dunn MJ. The clinical significance of inhibition of renal prostaglandin synthesis. Kidney Int 1987; 32:1.
  8. Perazella MA. COX-2 selective inhibitors: analysis of the renal effects. Expert Opin Drug Saf 2002; 1:53.
  9. Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med 2001; 111:64.
  10. Schneider V, Lévesque LE, Zhang B, et al. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol 2006; 164:881.
  11. Braden GL, O'Shea MH, Mulhern JG, Germain MJ. Acute renal failure and hyperkalaemia associated with cyclooxygenase-2 inhibitors. Nephrol Dial Transplant 2004; 19:1149.
  12. Dunn MJ. Are COX-2 selective inhibitors nephrotoxic? Am J Kidney Dis 2000; 35:976.
  13. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000; 35:937.
  14. Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med 2000; 133:1.
  15. Gooch K, Culleton BF, Manns BJ, et al. NSAID use and progression of chronic kidney disease. Am J Med 2007; 120:280.e1.
  16. Wei L, MacDonald TM, Jennings C, et al. Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function. Kidney Int 2013; 84:174.
  17. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis 2005; 45:531.
  18. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ 2013; 346:e8525.
  19. Delzer LM, Golightly LK, Kiser TH, et al. Calcineurin Inhibitor and Nonsteroidal Anti-inflammatory Drug Interaction: Implications of Changes in Renal Function Associated With Concurrent Use. J Clin Pharmacol 2018; 58:1443.
  20. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12:1063.
  21. Bonvalet JP, Pradelles P, Farman N. Segmental synthesis and actions of prostaglandins along the nephron. Am J Physiol 1987; 253:F377.
  22. Chou SY, Dahhan A, Porush JG. Renal actions of endothelin: interaction with prostacyclin. Am J Physiol 1990; 259:F645.
  23. Oliver JA, Pinto J, Sciacca RR, Cannon PJ. Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog. J Clin Invest 1980; 66:748.
  24. Scharschmidt LA, Dunn MJ. Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin. J Clin Invest 1983; 71:1756.
  25. Yared A, Kon V, Ichikawa I. Mechanism of preservation of glomerular perfusion and filtration during acute extracellular fluid volume depletion. Importance of intrarenal vasopressin-prostaglandin interaction for protecting kidneys from constrictor action of vasopressin. J Clin Invest 1985; 75:1477.
  26. Freeman RH, Davis JO, Villarreal D. Role of renal prostaglandins in the control of renin release. Circ Res 1984; 54:1.
  27. Ito S, Carretero OA, Abe K, et al. Effect of prostanoids on renin release from rabbit afferent arterioles with and without macula densa. Kidney Int 1989; 35:1138.
  28. Hébert RL, Jacobson HR, Breyer MD. PGE2 inhibits AVP-induced water flow in cortical collecting ducts by protein kinase C activation. Am J Physiol 1990; 259:F318.
  29. Ling BN, Kokko KE, Eaton DC. Inhibition of apical Na+ channels in rabbit cortical collecting tubules by basolateral prostaglandin E2 is modulated by protein kinase C. J Clin Invest 1992; 90:1328.
  30. Satoh T, Cohen HT, Katz AI. Intracellular signaling in the regulation of renal Na-K-ATPase. I. Role of cyclic AMP and phospholipase A2. J Clin Invest 1992; 89:1496.
  31. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984; 310:563.
  32. Takahashi K, Schreiner GF, Yamashita K, et al. Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat. J Clin Invest 1990; 85:1974.
  33. Heyman SN, Brezis M, Epstein FH, et al. Early renal medullary hypoxic injury from radiocontrast and indomethacin. Kidney Int 1991; 40:632.
  34. Perazella MA. Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol 2009; 4:1275.
  35. Weisbord SD, Bruns FJ, Saul MI, Palevsky PM. Provider use of preventive strategies for radiocontrast nephropathy in high-risk patients. Nephron Clin Pract 2004; 96:c56.
  36. Baker M, Perazella MA. NSAIDs in CKD: Are They Safe? Am J Kidney Dis 2020; 76:546.
  37. Zhan M, Doerfler RM, Xie D, et al. Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis 2020; 76:184.
  38. Plantinga L, Grubbs V, Sarkar U, et al. Nonsteroidal anti-inflammatory drug use among persons with chronic kidney disease in the United States. Ann Fam Med 2011; 9:423.
  39. Whelton A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Ann Intern Med 1990; 112:568.
Topic 7230 Version 28.0

References