Can testosterone therapy cause impaired renal function in patients with pre-existing kidney disease or those taking medications such as Angiotensin-Converting Enzyme (ACE) inhibitors or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Can Testosterone Damage Kidneys?

Testosterone therapy does not directly damage kidneys, but it should be used cautiously in patients with pre-existing renal insufficiency or congestive heart failure due to its potential to cause fluid retention, which can exacerbate these conditions. 1

Direct Renal Effects of Testosterone

Testosterone itself is not nephrotoxic and does not cause direct kidney damage. The primary renal concern with testosterone therapy relates to fluid retention and edema rather than intrinsic kidney injury 1:

• Fluid retention is uncommon and generally mild with testosterone replacement therapy 1
• The FDA label specifically warns that testosterone may promote retention of sodium and water, which can be problematic in patients with pre-existing cardiac, renal, or hepatic disease 2
• Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing renal disease 2

Testosterone Use in Chronic Kidney Disease

The evidence actually suggests that low testosterone levels are associated with worse outcomes in CKD patients, not that testosterone causes kidney damage 3, 4:

• Low testosterone is associated with an increased risk of all-cause mortality (pooled HR: 1.98,95% CI: 1.36-2.89) and cardiovascular events (pooled HR: 2.40,95% CI: 1.22-4.71) in men with CKD 3
• Testosterone replacement therapy in CKD patients (stages III-IV) has been shown to safely improve quality of life, hemoglobin levels, and grip strength without causing kidney function deterioration 5
• Testosterone can be administered to patients with end-stage renal disease without adjustment of doses used in hypogonadal men with normal renal function 6

Critical Drug Interactions That Can Affect Kidneys

The real kidney damage risk comes from combining testosterone with other medications that affect renal hemodynamics, not from testosterone alone:

ACE Inhibitors and ARBs

• These medications can cause acute kidney injury when combined with conditions that reduce renal perfusion 1
• ACE inhibitors should be temporarily suspended during intercurrent illness, volume depletion, or when testosterone-induced fluid retention occurs 1, 7
• A 10-20% increase in serum creatinine is expected and acceptable when initiating ACE inhibitors, but increases above 50% or creatinine >265 μmol/L (3 mg/dL) require dose reduction 1

NSAIDs

• NSAIDs are well-documented causes of kidney injury and should be avoided in patients with eGFR <30 mL/min/1.73 m² 1, 8
• The combination of NSAIDs with ACE inhibitors or testosterone (which can cause fluid retention) creates a triple threat for acute kidney injury 1
• NSAIDs reduce renal blood flow and can cause acute interstitial nephritis leading to proteinuria 8

Diuretics

• Overly aggressive diuresis combined with testosterone therapy can lead to volume depletion 1
• Diuretics should be reduced if testosterone causes fluid retention rather than discontinuing testosterone 1, 2

Monitoring Protocol for Testosterone in Renal Disease

Baseline assessment should include 1:

• Serum creatinine and estimated GFR
• Hematocrit or hemoglobin (testosterone increases these)
• Assessment of volume status and presence of edema

Follow-up monitoring 1:

• First visit at 1-2 months to assess fluid retention and hematocrit
• Subsequent visits every 3-6 months for the first year
• Monitor for signs of volume overload (weight gain, edema, dyspnea)

For patients on ACE inhibitors or ARBs concurrently 1, 8, 7:

• Check serum creatinine and potassium within 1 week of starting testosterone
• Counsel patients to temporarily hold ACE inhibitors/ARBs during illness, vomiting, diarrhea, or reduced oral intake 7
• Monitor for excessive creatinine increases (>30% from baseline) 7

Common Pitfalls to Avoid

1. Do not discontinue testosterone solely based on mild fluid retention - instead, adjust diuretic therapy or reduce other hypotensive agents 1, 2

2. Do not assume testosterone caused acute kidney injury - investigate for volume depletion, NSAID use, or bilateral renal artery stenosis first 1, 7

3. Do not withhold testosterone from CKD patients with hypogonadism - the evidence shows low testosterone is associated with worse outcomes, and replacement therapy is safe when monitored appropriately 3, 6, 5

4. Do not ignore the increased hematocrit - testosterone increases hemoglobin and hematocrit, which requires monitoring but is not a sign of kidney damage 1, 5

5. Do not combine testosterone with high-dose NSAIDs in patients with CKD - this combination significantly increases acute kidney injury risk 1, 8