What are the effects of Dehydroepiandrosterone (DHEA) on renal function?

Effects of DHEA on Renal Function

DHEA supplementation may have negative effects on renal function, potentially causing reduced glomerular filtration rate and increased renal damage in certain contexts. The available evidence suggests caution when considering DHEA use in patients with existing kidney conditions.

Effects of DHEA on Renal Function

Negative Effects

• DHEA treatment has been shown to reduce glomerular filtration rate and renal medulla metabolism in diabetic rats 1
• DHEA administration increased plasmatic creatinine levels and decreased creatinine clearance in experimental models 1
• DHEA treatment increased urinary excretion of Transforming Growth Factor β1 (TGF-β1), which is associated with renal fibrosis 1
• DHEA may have pro-oxidant or pro-fibrotic effects on renal tissue through mechanisms not fully understood 1

Potential Protective Effects

• In some ischemia/reperfusion injury models, DHEA pretreatment altered renal IL-1β, IL-6, and VEGF synthesis, suggesting some modulatory effect on inflammatory pathways 2
• DHEA has shown protective effects against oxidative damage in renal tissue during ischemia/reperfusion injury by preventing decreases in antioxidant enzyme activities 3
• DHEA administration (50 mg/kg) prior to ischemia maintained superoxide dismutase (SOD) and catalase (CAT) activities at normal levels and prevented increases in malondialdehyde (MDA), a marker of oxidative stress 3

Context-Dependent Effects

• In ovariectomized rats with pressure-induced kidney hypertrophy, DHEA (15-30 mg/kg) showed protective effects by:

  • Inhibiting hypertension-induced increases in kidney weight 4
  • Increasing expression of Sigma-1 receptor in the kidney 4
  • Restoring endothelial nitric oxide synthase (eNOS) activity 4
  • Increasing phosphorylation of eNOS and Akt activity 4

• In dexamethasone-treated rabbits, DHEA supplementation:

  • Reduced oxidative stress in kidney cortex 5
  • Decreased NADPH oxidase activity and enhanced catalase activity 5
  • Effectively attenuated dexamethasone-induced albuminuria 5
  • Normalized glutathione redox state 5

Monitoring Considerations

• Current guidelines do not provide specific recommendations for monitoring renal function during DHEA supplementation 6
• For patients with chronic kidney disease (CKD), regular monitoring of renal function is recommended at intervals appropriate to the CKD stage (e.g., every 3 months for CKD stages 3-4) 6
• Any unexplained decrease in estimated glomerular filtration rate (eGFR) should prompt consideration of discontinuing potentially nephrotoxic medications 6

Clinical Implications

• DHEA is commonly used as a supplement for female sexual dysfunction at doses of 10-50 mg daily 7
• Given the potential negative effects on renal function, patients with existing kidney disease should be monitored carefully if DHEA supplementation is considered 1
• The long-term effects of DHEA replacement therapy are not fully known, so such regimens should be used with caution 7
• For patients with both kidney disease and heart failure, careful monitoring of renal function is particularly important, as heart failure medications can also affect kidney function 6

Conclusion

The evidence regarding DHEA's effects on renal function is mixed and context-dependent. While some studies suggest protective effects in specific conditions like ischemia/reperfusion injury and glucocorticoid-induced kidney damage, others indicate potential harm through reduced glomerular filtration and increased fibrotic markers. Until more definitive human studies are available, DHEA supplementation should be approached with caution in patients with existing renal conditions, and renal function should be monitored regularly in those taking DHEA supplements.