Can hydrocortisone (cortisol) cause impaired renal (kidney) function?

Hydrocortisone and Kidney Function

Hydrocortisone does not typically cause kidney damage in standard therapeutic doses, but can impact renal function through alterations in cortisol metabolism, especially in patients with pre-existing kidney disease.

Effects of Hydrocortisone on Kidney Function

Normal Kidney Function and Cortisol

• The kidney plays a major role in cortisol metabolism, being the primary site for conversion of cortisol to cortisone through the enzyme 11β-hydroxysteroid dehydrogenase 1
• In healthy individuals, this enzyme helps regulate cortisol levels and prevents excessive cortisol activity 1

Impact in Kidney Disease

• In patients with chronic kidney disease (CKD), the conversion of cortisol to cortisone is impaired, leading to relative cortisol excess 2
• This impairment correlates with the severity of renal dysfunction, as demonstrated by the inverse relationship between serum creatinine and plasma cortisone levels 1
• The ratio of tetrahydrocortisone/tetrahydrocortisol is reduced in patients with chronic renal insufficiency, providing evidence of impaired cortisol-to-cortisone conversion 2

Potential Mechanisms and Consequences

• CKD can lead to subclinical hypercortisolism with blunted diurnal decline of cortisol levels, impaired negative feedback regulation, and reduced cortisol clearance 3
• This cortisol excess may contribute to complications seen in CKD, including hypertension, insulin resistance, dyslipidemia, and cardiovascular disease 3
• The relationship between cortisol dysregulation and hypertension in CKD patients has been observed, particularly in those with more severe renal impairment 2

Therapeutic Considerations

Beneficial Effects in Specific Conditions

• In septic acute kidney injury, hydrocortisone administration (50 mg IV every 6 hours) has been shown to improve renal function parameters and reduce 28-day mortality 4
• Hydrocortisone treatment in this context was associated with decreased inflammatory markers (IL-1β, IL-6, TNF-α) and improved glomerular filtration rate 4

Concerns in Drug-Induced Nephritis

• In drug-induced acute interstitial nephritis, corticosteroids are commonly used, but their efficacy depends on timing of initiation 5
• Delayed initiation of steroid treatment is associated with worse recovery of kidney function 5

Monitoring Recommendations

• For patients receiving immune checkpoint inhibitor therapy who develop nephritis, monitoring of serum creatinine is recommended prior to every dose 6
• Graded management approaches are recommended based on the severity of creatinine elevation, from temporary holding of therapy to permanent discontinuation and corticosteroid administration 6

Clinical Implications and Precautions

Risk Assessment

• Patients with pre-existing renal impairment may have altered cortisol metabolism and should be monitored more closely when receiving hydrocortisone therapy 2, 3
• The risk of adverse effects may be higher in patients with severe kidney disease due to reduced clearance of cortisol 1

Dosing Considerations

• In patients with adrenal insufficiency undergoing surgical procedures, hydrocortisone dosing should be adjusted based on the severity of the procedure and patient characteristics 6
• For pediatric patients with adrenal insufficiency, weight-based dosing is recommended (e.g., 2 mg/kg at induction for major surgery) 6

Common Pitfalls

• Failure to recognize altered cortisol metabolism in patients with kidney disease may lead to inappropriate dosing of hydrocortisone 3
• Not considering the potential impact of hydrocortisone on blood pressure control, especially in patients with kidney disease who already have a higher risk of hypertension 2

While hydrocortisone itself is not directly nephrotoxic, its effects on cortisol metabolism and clearance can impact kidney function, particularly in patients with pre-existing renal disease. Careful monitoring and appropriate dosing adjustments are essential to minimize potential adverse effects.