Testosterone Replacement Therapy and Renal Function
Testosterone replacement therapy (TRT) does not cause renal dysfunction but can lead to an increase in serum creatinine due to increased muscle mass, which may be misinterpreted as declining renal function. 1
Effects of TRT on Creatinine and Renal Function
Creatinine Changes
- TRT leads to approximately 4 kg increase in lean body mass after 1 year, resulting in higher creatinine production 1
- Serum creatinine typically increases from baseline (0.90 ± 0.10 mg/dL to 1.12 ± 0.9 mg/dL) with long-term TRT 2
- This increase reflects increased muscle mass rather than deteriorating kidney function 1
Actual Renal Function Impact
- Long-term TRT may actually improve glomerular filtration rate (GFR) from 87.0 ± 12.9 to 98.0 ± 8.0 mL/min/1.73 m² 2
- TRT has been associated with lower levels of urea (47.0 ± 11.8 to 34.0 ± 13.9 mg/dL) and uric acid (6.57 ± 1.2 to 5.49 ± 1.5 mg/dL) 2
- Cystatin C-based GFR estimation is recommended as it's less dependent on muscle mass, providing a more accurate assessment of renal function during TRT 1
Monitoring Recommendations
Before Starting TRT
- Establish baseline renal function before initiating TRT 1
- Consider using both creatinine and cystatin C-based GFR estimates for more accurate baseline assessment 1
During TRT
- Monitor renal function at 3-6 month intervals during testosterone therapy 1
- Interpret creatinine values in the context of increased muscle mass to avoid misinterpreting renal function 1
- Watch for unexplained decreases in eGFR not attributable to muscle mass changes 1
Special Considerations
Fluid Retention
- TRT can cause fluid retention, which should be considered in patients with compromised renal or cardiac function 3
- Use TRT cautiously in men with congestive heart failure or renal insufficiency 3
Patients with Existing Renal Disease
- Hypogonadism is common among men with chronic kidney disease (CKD), beginning before the need for dialysis 4
- Low testosterone is associated with increased mortality risk in men with stage 3 or greater nephropathy 5
- Men with kidney dysfunction and low testosterone have a more than 2-fold increased all-cause mortality risk (HR 2.52; 95% CI 1.08-5.85) 5
- Over half of patients with renal failure, even in pre-dialysis phase, have low or low-normal testosterone levels 6
When to Consider Discontinuing TRT
- If there is an unexplained decrease in eGFR not attributable to muscle mass changes 1
- In patients with persistent severe secondary hyperparathyroidism (PTH >500 pg/ml) 3
- In cases of significant fluid retention in patients with compromised renal function 3
Clinical Implications
- Avoid unnecessary adjustments to doses of renally-cleared medications based solely on creatinine-based eGFR in patients on TRT 1
- Consider the potential benefits of TRT in CKD patients, as low testosterone is associated with increased mortality and cardiovascular events 7
- TRT may potentially improve bone mineral density and libido in men with renal failure who have low testosterone 6
In conclusion, while TRT can increase serum creatinine due to increased muscle mass, it does not appear to cause renal dysfunction and may actually improve renal function parameters in hypogonadal men. Proper monitoring and interpretation of renal function tests in the context of TRT is essential.