Is testosterone therapy appropriate for patients with impaired renal function (low Glomerular Filtration Rate (GFR)) and elevated creatinine levels?

Testosterone Therapy in Patients with Low GFR and Elevated Creatinine

Testosterone therapy should be used with caution in patients with impaired renal function, but it is not contraindicated and may actually improve renal function in hypogonadal men with chronic kidney disease.

Assessment of Renal Function in Patients Considered for Testosterone Therapy

• Chronic kidney disease (CKD) is classified according to glomerular filtration rate (GFR) 1:

  • CKD 1: normal GFR ≥90 mL/min/1.73 m²
  • CKD 2: mildly decreased GFR 60-89 mL/min/1.73 m²
  • CKD 3a: mildly to moderately decreased GFR 45-59 mL/min/1.73 m²
  • CKD 3b: moderately to severely decreased GFR 30-44 mL/min/1.73 m²
  • CKD 4: severely decreased GFR 15-29 mL/min/1.73 m²
  • CKD 5: kidney failure GFR <15 mL/min/1.73 m² 2

• When evaluating renal function, consider using cystatin C-based GFR estimation rather than creatinine-based methods, as testosterone affects muscle mass and creatinine generation 2

Evidence Supporting Testosterone Use in Renal Impairment

Recent research provides encouraging evidence for testosterone therapy in patients with renal impairment:

• A long-term observational study showed that testosterone therapy in hypogonadal men improved renal function parameters over 8 years, including:

  • Increased GFR (87.0 to 98.0 mL/min/1.73 m²)
  • Decreased serum creatinine (0.90 to 1.12 mg/dL)
  • Decreased urea and uric acid levels 3

• Low testosterone levels in men with CKD are associated with increased risk of:

  • All-cause mortality (pooled HR: 1.98,95% CI: 1.36-2.89)
  • Cardiovascular events (pooled HR: 2.40,95% CI: 1.22-4.71) 4

• Testosterone therapy in end-stage renal disease (ESRD) patients can be administered without dose adjustment compared to hypogonadal men with normal renal function 5

Monitoring Recommendations

When prescribing testosterone to patients with impaired renal function:

1. Establish baseline renal function with both creatinine and cystatin C-based GFR if available
2. Monitor renal function every 3-6 months 1
3. Watch for unexplained decreases in GFR that may necessitate discontinuation of therapy
4. Monitor for electrolyte abnormalities, particularly if patient is also on medications like ACE inhibitors or ARBs 2
5. Evaluate cardiovascular risk factors, as patients with renal impairment have increased cardiovascular risk 1

Potential Benefits and Risks

Benefits:

• May improve muscle mass and bone mineral density in CKD patients 5
• Could potentially improve GFR and other renal parameters 3
• May reduce mortality risk in hypogonadal men with CKD 4, 3

Risks:

• Potential activation of the renin-angiotensin system 6
• Possible fluid retention
• Need for careful monitoring in patients with cardiovascular disease

Clinical Decision Algorithm

1. Confirm hypogonadism with appropriate laboratory testing
2. Assess severity of renal impairment using GFR estimation
3. For patients with mild to moderate renal impairment (CKD stages 1-3):
   • Standard testosterone replacement can be initiated with regular monitoring
4. For patients with severe renal impairment (CKD stages 4-5):
   • Consider nephrology consultation before initiating therapy
   • More frequent monitoring of renal function is warranted
5. Discontinue testosterone if:
   • Unexplained decrease in GFR occurs
   • Significant worsening of hypertension develops
   • Severe fluid retention occurs

Conclusion

While caution is warranted, testosterone therapy is not contraindicated in patients with low GFR and elevated creatinine. Recent evidence suggests potential benefits for renal function and mortality outcomes in hypogonadal men with CKD. Close monitoring is essential, with particular attention to changes in renal function parameters and cardiovascular risk factors.