Steroid-Dependent Nephrotic Syndrome in Pediatric Patients: Pharmacologic and Preventive Management
Lavanya. G
Clinical Pharmacist, Maa kauvery, Trichy, Tamil Nadu
Introduction
Steroid-Dependent Nephrotic Syndrome (SDNS) is a complex and chronic form of nephrotic syndrome in which pediatric patients require frequent courses of corticosteroids to maintain remission or prevent relapses. Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia, and the hallmark of SDNS is the recurrent need for corticosteroid therapy. The dependency on steroids, however, is concerning due to the potential for serious long-term adverse effects, including growth retardation, immunosuppression, hypertension, osteoporosis, and increased risk of infections.
This article provides a comprehensive review of the pharmacologic management of SDNS, including corticosteroid therapy, steroid-sparing agents, and prevention strategies to minimize steroid dependency along with a consolidated analysis of 3 pediatric SDNS cases. By optimizing treatment approaches, the goal is to reduce the adverse effects of long-term steroid use while maintaining disease control and preventing relapses.
Overview of Steroid-Dependent Nephrotic Syndrome
Nephrotic syndrome occurs when there is damage to the glomerular filtration barrier in the kidneys, leading to excessive protein leakage into the urine. In children, Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome and is frequently associated with steroid dependence. The hallmark of Steroid-Dependent Nephrotic Syndrome (SDNS) is the frequent relapses that occur once corticosteroid therapy is tapered or discontinued, necessitating repeated courses of steroids to maintain remission.
The initial treatment with corticosteroids usually leads to remission, but once therapy is reduced, proteinuria often returns. If this pattern continues, patients may become dependent on steroids to manage proteinuria and edema, making it difficult to discontinue treatment without causing a relapse. While steroids effectively manage While steroids effectively manage the disease, prolonged use can result in serious side effects, including growth retardation, immunosuppression, osteoporosis, and increased risk of cardiovascular diseases1.
Diagnosis and Evaluation
Diagnostic criteria for nephrotic syndrome
- Proteinuria: ≥3 + on urine dipstick or >40 mg/m2/hr
- Hypoalbuminemia: Serum albumin <3 g/Dl
- Edema and hyperlipidemia
SSNS is confirmed when proteinuria resolves within four weeks of corticosteroid therapy.
Indications for kidney Biopsy
A biopsy is recommended in cases of:
- Steroid resistance (failure to achieve remission after 6 weeks of prednisolone)
- Persistent microscopic or gross hematuria
- Systemic disease features (e.g., lupus, vasculitis)
- Prolonged calcineurin inhibitor therapy (> 30- 36 months)2
Management of the First Episode and Relapses
a) Corticosteroids: First-Line Treatment
Corticosteroids remain the mainstay for inducing remission in nephrotic syndrome. The typical corticosteroid used in pediatric SDNS is prednisone.
| Phase | Dosage | Duration |
|---|---|---|
| Induction Phase | Prednisone 2 mg/kg/day (maximum dose of 60 mg/day) | 6 weeks |
| Tapering Phase | Reduce prednisone by 40 mg/m2 on alternate days | 6 weeks and then stop |
For relapses, the same induction protocol is followed, but alternate-day steroids are continued for 4 weeks.
Challenges: Although corticosteroids are effective in inducing remission, they come with significant side effects when used long-term, such as growth retardation, bone demineralization, weight gain, and increased susceptibility to infections. Therefore, efforts are made to reduce the reliance on steroids as much as possible by incorporating steroid-sparing agents3.
Management of Frequent Relapses and Steroid Dependence
Frequent relapsing SSND and SDNS require steroid- sparing agents to reduce steroid toxicity and maintain remission.
a) Steroid-Sparing Agents
Steroid-sparing agents are used to maintain remission and reduce the long-term risks associated with corticosteroid therapy. These agents are particularly beneficial in children with frequent relapses or steroid-dependent nephrotic syndrome.
Calcineurin Inhibitors (CNIs)
| Drug | Initial dose | Monitoring |
|---|---|---|
| Cyclosporine | 5mg/kg/day divided into two doses | Maintain therapeutic levels between 100-250 ng/mL and avoid nephrotoxicity |
| Tacrolimus | 0.05 mg/kg/day divided into two doses | Blood levels should be maintained between 5-15 ng/mL |
Side effects
Cyclosporine – Potential nephrotoxicity, hypertension, and hyperkalemia.
Tacrolimus – Nephrotoxicity, hypertension, and hyperglycemia
Role of CNIs
Both cyclosporine and tacrolimus are effective at reducing proteinuria and maintaining remission without the need for high doses of corticosteroids. They are particularly useful in children with MCD and FSGS, where prolonged steroid use may be ineffective or lead to unacceptable side effects4.
Immunosuppressant
| Drug | Initial dose | Monitoring |
|---|---|---|
| Mycophenolate Mofetil (MMF) | 600 mg/m² twice daily (max 2 g/day) | Regular monitoring of blood counts |
Side effects: Gastrointestinal discomfort, myelosuppression and infections.
Role of MMF: MMF is commonly used for relapsing or steroid-dependent nephrotic syndrome in patients who have frequent relapses despite adequate steroid therapy. It is often used in combination with corticosteroids or CNIs to reduce steroid reliance.
Monoclonal Antibody
| Drug | Initial dose | Monitoring |
|---|---|---|
| Rituximab | 375 mg/m² once weekly for 4 weeks | Monitor for infections, immunoglobulin levels |
Side effects: Risk of infections, infusion related reactions
Role of Rituximab: It targets CD20-positive B-cells and especially effective in children with frequent relapses or those who have not responded to steroid-sparing agents such as cyclosporine or MMF5.
b) Supportive Medications2
| Drug class | Drug | Initial dose | Monitoring |
|---|---|---|---|
| Diuretics | Furosemide (Lasix) | 1 mg/kg/day, adjusted based on the severity of edema | Regular monitoring of electrolytes to prevent hypokalemia |
| Angiotensin-Converting Enzyme | Enalapril or lisinopril | 0.1 mg/kg/day, which may be increased based on response and tolerance | Monitor renal function, serum potassium, and blood pressure regularly |
| Statins | Atorvastatin | 10-20 mg per day, adjusted based on lipid levels | Lipid profile monitoring |
Preventing Steroid Dependency in Pediatric Nephrotic Syndrome
Preventing the development of steroid dependency is crucial in the management of pediatric nephrotic syndrome. Several strategies can help reduce the need for prolonged steroid use and minimize the associated risks.
Proactive and Intensive Treatment Approach
Induction with steroids should be done early, using the appropriate dose (e.g., 2 mg/kg/day of prednisone) for inducing remission. If frequent relapses occur, steroid-sparing agents should be introduced as early as possible to prevent steroid dependency.
Steroid-Sparing Agents: Early introduction of cyclosporine, tacrolimus, or MMF in patients with frequent relapses or steroid resistance can help maintain remission and reduce reliance on steroids6.
Regular Monitoring
Proteinuria: Regular assessment of proteinuria using the urine protein-to-creatinine ratio or 24-hour urine collection is essential to detect relapses early. Early intervention with additional immunosuppressive therapy can prevent escalation to more intense steroid treatments.
Kidney Function: Regular monitoring of serum creatinine and eGFR is necessary to evaluate kidney function, especially in patients receiving long-term immunosuppressive therapy such as cyclosporine or tacrolimus.
Infection Control
Children receiving corticosteroids or other immunosuppressive agents are at increased risk of infections, which may trigger relapses. Preventive strategies include:
Vaccinations: Ensuring that patients are vaccinated against infections such as influenza, pneumococcal, and hepatitis.
Infection Prophylaxis: In some cases, antibiotics or antiviral prophylaxis may be recommended, especially during periods of active treatment with immunosuppressive agents7.
Case Studies Discussion
In a consolidated evaluation of three pediatric patients aged 4, 6, and 8 years with a confirmed diagnosis of steroid-dependent nephrotic syndrome (SDNS), a consistent yet individualized therapeutic approach was observed, reflecting real-world management challenges and strategies. All patients presented with clinical features characteristic of relapse, such as periorbital and pedal edema, abdominal distension, decreased urine output, and in some cases, gastrointestinal symptoms (vomiting, loose stools) and respiratory tract involvement (cough, coryza).
Notably, the 4-year-old exhibited spontaneous bacterial peritonitis (SBP) and a suspected allergic reaction to human albumin infusion, underlining the spectrum of complications in SDNS and the need for heightened clinical vigilance during inpatient care.
Management across all cases prioritized high-dose corticosteroid therapy, primarily oral prednisolone (Omnacortil), administered at doses ranging from 20 mg to 60 mg per day, followed by tapering schedules customized to individual responses.
Diuretics such as furosemide and spironolactone were used for fluid overload management, discontinued due to dehydration. Gastroprotection using pantoprazole or lansoprazole was incorporated to minimize steroid-associated gastrointestinal risks, and bone health was supported with calcium and vitamin D3 supplementation (Shelcal, Calcimax) to counteract the long-term risk of steroid-induced osteopenia.
In the case involving prior tacrolimus use, immunosuppression was temporarily withheld due to acute illness, pending further review by the primary nephrologist—highlighting the complexity of balancing immunomodulation in SDNS management.
Preventive and supportive care formed an integral part of the discharge planning. All children were provided with tailored advice regarding nutrition, fluid intake, and infection prevention. Two patients presented with obesity (BMI >90th percentile), and structured counseling on weight management and lifestyle modification was initiated. Vaccination status was reviewed and found to be up-to-date in all cases; nevertheless, reinforcement of pneumococcal and influenza vaccinations was advised due to the high relapse risk associated with infections.
Education of caregivers regarding the signs of relapse, the importance of medication adherence, and prompt medical consultation in the event of infections or steroid tapering was emphasized as a cornerstone of relapse prevention.
These cases collectively illustrate the multifaceted nature of SDNS in pediatric populations, the necessity for dynamic pharmacologic regimens, and the critical importance of integrating preventive strategies alongside acute management. The interplay between immunosuppression, infection control, and nutritional support underscores the complexity of SDNS treatment and the need for a multidisciplinary approach to reduce morbidity and preserve renal function over the long term.
Conclusion
Steroid-Dependent Nephrotic Syndrome (SDNS) in pediatric patients requires a comprehensive treatment approach that includes corticosteroids for induction, steroid-sparing agents to reduce dependency, and supportive care to manage complications such as edema and hyperlipidemia. The management of SDNS must focus on achieving remission while minimizing the long-term adverse effects of corticosteroid therapy. Early initiation of appropriate treatment, including the use of calcineurin inhibitors, mycophenolate mofetil, or rituximab, can significantly reduce steroid dependency and improve long-term outcomes in pediatric patients with nephrotic syndrome.
References
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- Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS. The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatric nephrology. 2003 Sep; 18:919-24.
- Benz K, Dötsch J, Rascher W, Stachel D. Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatric Nephrology. 2004 Jul; 19:794-7.
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