INTRODUCTION Nephrotic syndrome is a prevalent glomerular disorder affecting children worldwide. It is characterized by significant proteinuria ( >3.5 gm/24 hr urine or protein: creatinine ratio >2), hypoalbuminemia( < 2.5 gm/ dL) , pitting edema, hyperlipidemia and hypercholesterolemia( > 200 gm/ dL). Minimal change disease is the most common cause of nephrotic syndrome in children. Effective management of pediatric nephrotic syndrome requires a thorough understanding of its clinical features, acceptable and sensitive diagnostic techniques, timely implementation of the treatment modalities while monitoring compliance, and efforts to mitigate the potential complications while being able to deal with the same if the untoward occurrences still occur.
AETIOLOGY 1) Idiopathic Nephrotic Syndrome -Minimal change diseases - only steroid sensitive type -Focal segmental glomerulosclerosis -Membranous nephropathy -Membranoproliferative glomerulonephritis( Type 1 and Type 2) 2) Nephrotic Syndrome that occurs secondary to certain systemic diseases Due to hyperactivity of the immune system as in infections, autoimmune diseases and malignancies. 3) Congenital Nephrotic Syndrome Mutations in genes like NPHS-1 (Nephrin), NPHS-2 (Podocin), WT-1 (Wilms Tumor Suppressor gene) and others.
CLINICAL FEATURES Nephrotic syndrome initially presents with edema, typically periorbital and ankle edema, along with weight gain due to fluid retention in the extra vascular space( but may be associated with intravascular volume depletion in certain cases). Ascites, pleural effusion and pulmonary oedema can occur in severe cases and at later stages of the disease. Foamy urine resulting from increased protein excretion is a frequent observation.
Additional symptoms include fatigue, decreased appetite, and an increased susceptibility to infections. Nephrotic features like hypertension and hematuria are rare. Hypercoagulable state due to urinary loss of anti-thrombin 3 and increased synthesis of clotting factors like fibrinogen .
DIAGNOSTIC APPROACH Diagnosing nephrotic syndrome in children is via a comprehensive approach. A thorough and exhaustive history taking is a crucial step in establishing the diagnosis. Additional supportive evidence is gathered by carrying out laboratory examinations of urine sample (dipstick and quantitative tests for proteinuria, microscopic hematuria, though first morning urine protein:creatinine ratio is confirmatory test). Blood tests involving serum albumin, lipid profile, serum electrolytes, blood urea nitrogen and creatinine and serum complement levels. Renal biopsy may be performed in certain cases with atypical presentation or in older children who are more likely to have FSGS. A renal biopsy is not routinely performed if the diagnosis is established by clinical findings only. Additional Tests: Complement C3 levels, Anti-nuclear antibody and evaluation for Hepatitis B, Hepatitis C and HIV. Congenital nephrotic syndrome is caused due to defect in NPHS- 1/2, WT-1 gene which can be detected by using PCR, next generation sequencing or whole genome sequencing techniques.
Diagnostic Criteria and Findings 3+ or 4+ proteinuria Urine protein: creatinine ratio >2 Serum albumin < 2.5 gm/ dL Serum Cholesterol >200gm /dL Serum complement levels are normal.
TREATMENT The management of pediatric nephrotic syndrome aims to achieve remission, minimize relapses, and prevent complications. The primary treatment modalities include:
Corticosteroids: Oral prednisone is the cornerstone of therapy for inducing remission. Typically, it is administered in dosage of 2 mg/kg/day daily( 60 mg is the maximum dose) for 4-6 weeks, followed by an alternate day regimen with dose of 1.5 mg/kg/qod for a duration of 8 weeks to 5 months and is then tapered off. Corticosteroids help reduce proteinuria and control kidney inflammation.
Diuretics: Loop diuretics, such as furosemide, may be prescribed to manage edema and fluid retention. These medications increase urine output and alleviate kidney burden.
Dietary Modifications:A low sodium diet (<1500 mg daily) is often advised to manage fluid retention. This entails reducing the consumption of processed foods and incorporating fresh fruits and vegetables into the child's diet. Adequate protein intake should be ensured to compensate for urinary protein losses. Fluid/ Water restriction is sometimes advised if the child is hyponatremic.
Immunomodulatory Agents: In cases of steroid-resistant or frequently relapsing nephrotic syndrome, immunomodulatory agents like calcineurin inhibitors (e.g., cyclosporine) or rituximab (a monoclonal antibody against CD20 B-cell receptor) may be considered to achieve remission and reduce the reliance on long-term steroid use.
Supportive Care: Managing complications, such as infections and thromboembolism, is essential. Vaccination against pneumococcal and influenza infections is recommended, though viral vaccines are often avoided as in cases of varicella exposure when VZIG are usually administered. Vaccinating the child’s family members and avoiding contact with the infected ones is also recommended. Anticoagulant therapy may be considered in high-risk cases. Heparin, LMW- Heparin and Warfarin are the various options.
Psychological Therapy: For proper behavioural and cognitive child development, the children with idiopathic nephrotic syndrome should be well counselled and asked to participate in daily activities and have a non restricted diet in the periods of remission.
POTENTIAL COMPLICATIONS It can lead to various complications as listed below:
Infections: Children with nephrotic syndrome are more susceptible to infections due to immune dysfunction and hypogammaglobulinemia. Spontaneous bacterial peritonitis as ascitic fluid acts as a good culture medium for bacterial growth, septicemia, cellulitis etc. are some of the examples. Prompt identification and treatment of infections are crucial to prevent further kidney damage.
Thromboembolism: The loss of antithrombin III and increased production of fibrinogen can predispose children with nephrotic syndrome to hypercoagulability state and can even lead to DIC. Prophylactic measures, such as anticoagulant therapy and regular mobilization, should be considered of high value in high-risk cases.
Growth Impairment and Obesity: Chronic steroid use, delayed puberty, and altered nutritional status can affect growth and development in children with nephrotic syndrome. Long term steroid use in overweight children can increase their BMI.Regular monitoring of growth parameters i.e. anthropometry, appropriate nutritional advice and steroids sparing strategies are vital.
Long-term Renal Complications: Certain forms of nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) have a poor prognosis , and often progress to End- Stage renal disease. Close and regular monitoring of renal function and blood pressure, is essential to detect and manage potential complications at an early stage.
CONCLUSION Effectively managing nephrotic syndrome is a multidisciplinary task involving doctors from various specialities including pediatric nephrologists,daily physicians, and dietiticians. Early diagnosis, appropriate treatment with corticosteroids or immunomodulatory agents as indicated, and close monitoring for acute exacerbations and long term complications is crucial for achieving remission, minimizing relapses, and preserving long-term kidney function. With timely intervention and comprehensive care, children with nephrotic syndrome can lead healthy and fulfilling lives.
WRITER- KANIKA HANDU
EDITOR- JASMINE
PROMOTER- HEER
REFERENCES
1. Zamora G, Pearson-Shaver AL. Minimal Change Disease. [Updated 2022 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560639/
2. Tapia C, Bashir K. Nephrotic Syndrome. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470444/
3. Jalanko H. Congenital nephrotic syndrome. Pediatr Nephrol. 2009;24(11):2121-2128. Doi:10.1007/s00467-007-0633-9
4. Gupta S, Pepper RJ, Ashman N, Walsh SB. Nephrotic Syndrome: Oedema Formation and Its Treatment With Diuretics. Front Physiol. 2019;9:1868. Published 2019 Jan 15. Doi:10.3389/fphys.2018.01868
5. Viteri B, Reid-Adam J. Hematuria and Proteinuria in Children. Pediatr Rev. 2018;39(12):573-587. Doi:10.1542/pir.2017-0300
6. Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015;2015(3):CD001533. Published 2015 Mar 18. Doi:10.1002/14651858.CD001533.pub5
7. Bagga A. Revised guidelines for management of steroid-sensitive nephrotic syndrome. Indian J Nephrol. 2008;18(1):31-39. Doi:10.4103/0971-4065.41289
8. Park SJ, Shin JI. Complications of nephrotic syndrome [published correction appears in Korean J Pediatr. 2012 Apr;55(4):151]. Korean J Pediatr. 2011;54(8):322-328. Doi:10.3345/kjp.2011.54.8.322
9. Göknar N, Webb H, Waters A, Tullus K. Long-term obesity prevalence and linear growth in children with idiopathic nephrotic syndrome: is normal growth and weight control possible with steroid-sparing drugs and low-dose steroids for relapses?. Pediatr Nephrol. 2022;37(7):1575-1584. Doi:10.1007/s00467-021-05288-1
10. Indian Pediatric Nephrology Group, Indian Academy of Pediatrics, Bagga A, Ali U, et al. Management of steroid sensitive nephrotic syndrome: revised guidelines. Indian Pediatr. 2008;45(3):203-214.