Which kidney diseases should we avoid using diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) injections in?

Kidney Diseases Requiring Avoidance of Diclofenac Injection

Diclofenac injections should be completely avoided in patients with advanced renal disease (CKD stages 4-5, GFR <30 mL/min/1.73 m²), acute kidney injury, and in any patient with pre-existing kidney disease who is taking ACE inhibitors, ARBs, or diuretics due to the extremely high risk of acute kidney injury and progression to chronic kidney disease. 1, 2

Absolute Contraindications

Advanced Chronic Kidney Disease

• Patients with GFR <30 mL/min/1.73 m² (CKD stages 4-5) should never receive diclofenac, as the FDA label explicitly states that "treatment with diclofenac is not recommended in these patients with advanced renal disease" 2
• The KDOQI guidelines specifically state that NSAIDs should be avoided in people with GFR <30 mL/min/1.73 m² 1
• Even a single dose of diclofenac in the setting of pre-existing subclinical acute kidney injury can cause progression to chronic kidney disease 3

Acute Kidney Injury (Any Stage)

• Diclofenac is absolutely contraindicated in patients with active acute kidney injury, as NSAIDs cause dose-dependent reduction in prostaglandin formation and renal blood flow, which precipitates overt renal decompensation 2
• Patients with pre-existing subclinical AKI who receive diclofenac experience aggravated acute tubular injury and develop interstitial fibrosis and tubular atrophy 3

Dialysis Patients

• While not an absolute contraindication, diclofenac should be avoided in dialysis patients due to concerns about sodium and water retention, worsening volume overload, hypertension, heart failure, and hyperkalemia 4
• The primary kidney function concern is eliminated, but cardiovascular and fluid management complications become critical 4

High-Risk Kidney Conditions Requiring Extreme Caution or Avoidance

Moderate Chronic Kidney Disease (Stage 3)

• Prolonged NSAID therapy is not recommended for patients with GFR <60 mL/min/1.73 m² (CKD stages 3-5) 1
• For patients with GFR 30-60 mL/min/1.73 m², use only the lowest effective dose for the shortest duration if absolutely necessary 1
• Monitor renal function weekly for the first 3 weeks in these high-risk patients 1

Nephrotic Syndrome

• Patients with nephrotic syndrome should avoid NSAIDs due to their dependence on prostaglandins for maintaining renal perfusion in the setting of hypoalbuminemia and reduced effective circulating volume 5
• NSAIDs eliminate the protective vasodilatory effect of prostaglandins, causing renal vasoconstriction and decreased renal blood flow 1

Glomerular Diseases

• Patients with active glomerulonephritis, membranous nephropathy, IgA nephropathy, or other glomerular diseases should avoid diclofenac 5
• These conditions already compromise renal function, and NSAIDs can precipitate acute-on-chronic kidney injury 5

Acute Interstitial Nephritis

• Diclofenac is contraindicated in patients with a history of NSAID-induced acute interstitial nephritis, as this represents a hypersensitivity reaction that can recur with re-exposure 5
• Acute interstitial nephritis is the most common pathology (80-90%) in immune checkpoint inhibitor-related renal dysfunction, and concomitant NSAID use is a known risk factor 5

Critical High-Risk Combinations to Avoid

The "Triple Whammy"

• Never use diclofenac in patients taking both ACE inhibitors/ARBs AND diuretics, regardless of baseline kidney function 1
• This combination eliminates both vasodilatory mechanisms (prostaglandins) and pressure-maintaining mechanisms (angiotensin II), dramatically increasing acute kidney injury risk 1
• NSAIDs should not be used in CKD patients taking RAAS blocking agents 1

Congestive Heart Failure with Renal Impairment

• Patients with heart failure and any degree of renal impairment should avoid diclofenac entirely 2
• The FDA label warns that "patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly" 2
• Prostaglandins have a compensatory role in maintaining renal perfusion in heart failure patients 2

Volume Depletion States

• Diclofenac should not be initiated in patients with considerable dehydration or volume depletion 2
• Volume-depleted patients with any underlying kidney condition have dramatically increased acute kidney injury risk 1

Special Populations Requiring Avoidance

Elderly Patients with Any Renal Impairment

• The ADQI consensus recommends avoiding NSAIDs in elderly patients with creatinine clearance <30 mL/min 1
• Elderly patients are at greatest risk for NSAID-induced renal decompensation 2

Patients on Tenofovir Therapy

• Diclofenac should be avoided in patients taking tenofovir disoproxil fumarate (TDF), as drug-drug interaction exacerbates TFV-associated nephrotoxicity 6
• In one cohort, 14.6% of TDF-treated patients developed acute kidney injury shortly after initiating diclofenac, with all cases showing proximal tubular damage 6

Monitoring Requirements If Diclofenac Cannot Be Avoided

For Mild CKD (Stage 2, GFR 60-89 mL/min/1.73 m²)

• Obtain baseline serum creatinine before starting therapy 1
• Monitor renal function weekly for the first 3 weeks 1
• Ensure adequate hydration status 1
• Avoid concomitant nephrotoxic medications 1
• Use the lowest effective dose for the shortest duration 1

Critical Pitfalls to Avoid

• Do not assume that short-term use is safe in patients with pre-existing kidney disease - even a single dose can cause progression to chronic kidney disease in vulnerable patients 3
• Do not rely on stable baseline creatinine - patients can have subclinical kidney injury that becomes clinically apparent only after NSAID exposure 3
• Do not overlook drug interactions - always review the complete medication list for RAAS blockers, diuretics, and other nephrotoxic agents 1

Preferred Alternatives in Kidney Disease

• Acetaminophen is the preferred first-line analgesic for patients with any degree of kidney disease, with a recommended dose of up to 3 grams daily 1
• For inflammatory conditions, consider low-dose colchicine or intra-articular/oral glucocorticoids 1
• For severe pain, consider low-dose opioids without active metabolites (methadone, buprenorphine, or fentanyl) 1