Overview
Definition:
Nephrotic syndrome is a clinical condition characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia
A relapse is defined as the recurrence of significant proteinuria (urine protein-to-creatinine ratio >= 2 mg/mg or 24-hour urine protein excretion >= 3.5 g/day) after a period of remission (urine protein-to-creatinine ratio < 0.2 mg/mg or 24-hour urine protein excretion < 1 g/day)
Relapses are common in children with nephrotic syndrome, particularly in cases of idiopathic nephrotic syndrome (INS).
Epidemiology:
Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children, with an incidence of approximately 2-7 cases per 100,000 children per year
A significant proportion of children with INS experience relapses, with estimates varying from 40-80% experiencing at least one relapse
Children with frequently relapsing (4 or more relapses in 12 months) or steroid-dependent nephrotic syndrome are at higher risk of complications.
Clinical Significance:
Frequent relapses of nephrotic syndrome can lead to significant morbidity for the child and distress for the family
Recurrent edema, infections, thromboembolic events, and long-term steroid toxicity are major concerns
Effective relapse management strategies are crucial for achieving prolonged remission, minimizing complications, and improving the quality of life for affected children
This topic is highly relevant for DNB and NEET SS pediatrics examinations, testing understanding of diagnosis, treatment protocols, and family counseling.
Clinical Presentation And Diagnosis
Signs And Symptoms:
Edema: often starting in the periorbital area, progressing to generalized anasarca
Ascites
Pleural effusions
Weight gain
Decreased urine output
Irritability
Lethargy
Abdominal pain
Diarrhea
Respiratory distress if significant effusions.
Diagnostic Criteria For Relapse:
Recurrence of nephrotic-range proteinuria (urine protein-to-creatinine ratio (UPCR) ≥ 2 mg/mg or 24-hour urine protein ≥ 3.5 g/day) after a documented period of remission (UPCR < 0.2 mg/mg or 24-hour urine protein < 1 g/day)
Remission is typically defined as absence of edema and presence of urine protein excretion < 1 g/day or UPCR < 0.2 mg/mg for at least three consecutive days.
Initial Assessment And Investigations:
Urine dipstick for proteinuria and hematuria
Urine protein-to-creatinine ratio (UPCR) or 24-hour urine protein quantification
Serum albumin and total protein
Serum electrolytes, BUN, creatinine
Complete blood count
Lipid profile
Coagulation profile (PT, aPTT, INR) if suspected thrombosis
Blood culture if febrile.
Relapse Management For Families
Initial Management At Home:
Monitor urine protein daily using dipsticks
Recognize early signs of relapse (e.g., periorbital edema upon waking, weight gain)
Limit fluid intake if significant edema is present
Maintain a low-salt diet
Monitor weight daily
Contact the healthcare provider promptly if relapse is suspected.
Role Of Steroids In Relapse:
For children with frequently relapsing or steroid-dependent nephrotic syndrome, a predefined relapse protocol often involves re-initiation of corticosteroids, usually at the same dose used for initial remission, for a specified duration
For steroid-sensitive nephrotic syndrome (SSNS), treatment is guided by the treating physician, typically involving a short course of oral prednisone (e.g., 2 mg/kg/day, max 60 mg/day) or equivalent, tapered over several weeks once remission is achieved
For steroid-resistant nephrotic syndrome (SRNS), different immunosuppressive agents are considered.
Managing Edema:
Diuretics (e.g., furosemide, spironolactone) may be prescribed if edema is severe and unresponsive to dietary salt restriction and fluid management
Intravenous albumin infusion followed by furosemide is indicated for severe, symptomatic edema (anasarca, significant respiratory compromise).
Dietary Recommendations:
Low-salt diet is crucial to prevent fluid retention
Adequate protein intake should be maintained
Avoid excessive fluid intake, especially during periods of significant edema
Consultation with a dietitian can be beneficial.
Prevention Of Relapses And Complications
Strategies For Prevention:
Identifying triggers: Viral infections and immunizations are common triggers for relapses
prompt treatment of infections and careful timing of vaccinations may help
Adherence to maintenance therapy: For steroid-dependent cases, consistent adherence to low-dose steroid therapy or alternative immunosuppressants is key
Education: Empowering families with knowledge about the disease, early signs of relapse, and management strategies is vital.
Infection Prevention:
Vaccination: Pneumococcal and influenza vaccines are highly recommended
Prompt treatment of infections: Any signs of infection should be immediately evaluated and treated
Prophylactic antibiotics may be considered in specific high-risk situations (e.g., severe hypoalbuminemia).
Thromboembolic Prophylaxis And Management:
Risk factors include hypoalbuminemia (< 20 g/L), rapid diuresis, immobility, and previous thrombosis
Anticoagulation (e.g., low molecular weight heparin) is indicated in patients with suspected or confirmed venous or arterial thrombosis, or in cases of severe hypoalbuminemia with multiple risk factors
Regular monitoring of coagulation parameters may be necessary.
Steroid Sparing Agents:
For children with frequently relapsing or steroid-dependent nephrotic syndrome, steroid-sparing agents such as cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors (e.g., cyclosporine, tacrolimus) may be used to reduce the frequency of relapses and minimize corticosteroid-related side effects
These are typically initiated after achieving remission and require careful monitoring.
Family Education And Support
Empowering Families:
Provide clear, written information about nephrotic syndrome, its relapsing nature, and the management plan
Encourage active participation in decision-making
Foster open communication channels with the healthcare team
Explain the rationale behind treatments and potential side effects.
Recognizing Red Flags:
Teach families to identify signs of severe edema (difficulty breathing, reduced urine output), signs of infection (fever, lethargy), or signs of thrombosis (sudden onset of limb swelling, pain, chest pain)
Emphasize the importance of seeking immediate medical attention for these symptoms.
Psychosocial Support:
Acknowledge the emotional toll of managing a chronic illness with relapses
Provide resources for psychological support for both the child and family
Connect families with support groups or patient advocacy organizations.
Key Points
Exam Focus:
Differentiating SSNS from SRNS
Understanding criteria for relapse, remission, frequently relapsing, and steroid-dependent nephrotic syndrome
Management protocols for relapses, including steroid re-initiation, diuretics, and albumin
Indications for steroid-sparing agents and their monitoring
Recognition and management of complications like infections and thrombosis
Family education is a critical component for successful management.
Clinical Pearls:
Always consider infection as a precipitating factor for relapse
Daily weight monitoring is a simple yet effective tool for early detection of fluid retention
Be vigilant for thromboembolic events, especially in children with severe hypoalbuminemia
Steroid-sparing agents should be initiated by experienced nephrologists and require close monitoring for efficacy and toxicity.
Common Mistakes:
Delaying treatment for a suspected relapse
Inadequate management of edema leading to respiratory compromise
Over-reliance on diuretics without addressing underlying hypoalbuminemia
Inappropriate use or lack of monitoring of steroid-sparing agents
Failing to adequately educate and involve the family in the management plan
Underestimating the risk of infections in immunosuppressed children.