What are the side effects of prednisolone in nephrotic syndrome?

Side Effects of Prednisolone in Nephrotic Syndrome

Prednisolone therapy in nephrotic syndrome causes significant adverse effects including growth retardation, osteoporosis, hypertension, behavioral disturbances, infection risk, diabetes, cataracts, and cushingoid features, with the severity and frequency directly related to cumulative dose and duration of therapy. 1, 2

Common Steroid-Related Side Effects

The most frequently encountered adverse effects in patients with steroid-dependent nephrotic syndrome include:

• Growth impairment and short stature - particularly problematic in pediatric patients requiring prolonged therapy 2
• Hypertension - requires regular blood pressure monitoring throughout treatment 1, 3
• Behavioral disturbances and psychiatric symptoms - can be severe enough to contraindicate high-dose steroid therapy 1
• Osteoporosis and bone loss - bone protection should be implemented according to local guidelines when prescribing glucocorticoids 1
• Increased infection risk - pneumocystis pneumonia prophylaxis is recommended when using prednisone equivalent ≥0.5 mg/kg/day 1

Metabolic and Endocrine Complications

• Diabetes mellitus - uncontrolled diabetes represents a relative contraindication to high-dose steroid therapy 1, 4
• Cushingoid features - common with prolonged exposure 4
• Weight gain and fluid retention - frequently observed 2

Gastrointestinal Effects

• Gastropathy risk - gastroprotection should be provided when prescribing glucocorticoids according to local guidelines 1

Ophthalmologic Complications

• Cataracts - develop with long-term use 4

Critical Monitoring to Detect Side Effects

Regular surveillance is essential during prednisolone therapy:

• Serum creatinine and GFR - monitor kidney function 5, 3
• Potassium levels - especially important in patients with congestive heart failure, hypertension, or renal insufficiency 1
• Blood pressure - check frequently 1, 3
• Growth parameters - height percentiles should be tracked in pediatric patients 6
• Bone density - assess for osteopenia development 2

Strategies to Minimize Toxicity

The key principle is balancing efficacy with minimizing cumulative steroid exposure through appropriate treatment duration and consideration of steroid-sparing agents. 7

Optimal Initial Treatment Duration

• Longer initial courses (up to 6 months) paradoxically result in lower cumulative steroid doses compared to shorter courses, because they reduce relapse rates 7, 3
• Studies show that 2-month courses resulted in 81% relapse rates versus 59% with 6-month courses 3
• Despite higher initial exposure, the reduced relapse frequency means less total steroid exposure over time 7

When to Use Steroid-Sparing Agents

For patients with frequent relapses or steroid-dependent disease, second-line agents should be considered to limit corticosteroid toxicity:

• Cyclophosphamide - induces long-term remissions in 25-70% of children, with total doses below 200 mg/kg minimizing gonadal toxicity risk 4
• Calcineurin inhibitors (cyclosporine or tacrolimus) - produce complete remissions in 85% of children and 79% of adults with steroid dependence 7, 4
• Levamisole - may be helpful in steroid-dependent cases 4
• Mycophenolate mofetil - alternative option for patients with contraindications to other agents 1

Specific Contraindications to High-Dose Steroids

Patients with the following conditions should receive alternative immunosuppression rather than high-dose prednisolone:

• Uncontrolled diabetes mellitus 1
• Severe psychiatric conditions 1
• Severe osteoporosis 1

Comparative Toxicity: Prolonged vs. Standard Therapy

• A 16-week prednisolone course for initial episodes resulted in significantly more steroid toxicity compared to 8-week courses, despite delaying first relapse 8
• The mean prednisolone dose received (initial episode plus relapses during the next year) was higher with prolonged treatment 8
• However, guidelines still favor longer courses because the overall cumulative exposure remains lower when accounting for reduced relapses over years of follow-up 7, 3

Low-Dose Maintenance Strategy

• Daily low-dose prednisolone (0.25 mg/kg/day) for 18 months in frequently relapsing patients reduced relapse frequency from 3.62 to 0.5 relapses per patient per year 6
• No side effects were observed with this low-dose regimen, and height percentiles improved or remained unchanged in all patients 6
• This approach may be preferable to repeated high-dose courses in selected patients 6

Special Population Considerations

Canadian Health Care Context

• The Canadian Society of Nephrology working group does not support low-dose daily or alternate-day maintenance corticosteroids for steroid-dependent patients when second-line agents are available, due to superior evidence for alternative therapies 7

Patients with Advanced CKD

• Avoid immunosuppressive therapy in patients with GFR <30 mL/min/1.73 m² unless crescentic glomerulonephritis with rapidly deteriorating kidney function is present 5