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Table of Contents
EDITORIAL COMMENTARY
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 45-47

Nephrotic syndrome: Indian society of pediatric nephrology management guidelines


Division of Pediatric Nephrology, Indraprastha Apollo Hospitals, New Delhi, India

Date of Submission11-Nov-2021
Date of Decision22-Nov-2021
Date of Acceptance24-Nov-2021
Date of Web Publication28-Dec-2021

Correspondence Address:
Rajendra Nath Srivastava
487, Mandakini Enclave, Alaknanda, New Delhi - 110 019
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajpn.ajpn_37_21

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How to cite this article:
Srivastava RN. Nephrotic syndrome: Indian society of pediatric nephrology management guidelines. Asian J Pediatr Nephrol 2021;4:45-7

How to cite this URL:
Srivastava RN. Nephrotic syndrome: Indian society of pediatric nephrology management guidelines. Asian J Pediatr Nephrol [serial online] 2021 [cited 2022 Jan 17];4:45-7. Available from: https://www.ajpn-online.org/text.asp?2021/4/2/45/334038




  Background Top


Nephrotic syndrome in children was well recognized over many years as a common condition, which was difficult to treat and lead to considerable mortality.[1] Availability of antibiotics and effective diuretic agents resulted in a marked improvement in the eventual outcome, as the disorder resolved in a large proportion of cases around the age of puberty. Introduction of corticosteroids as a specific antiproteinuric agent in these patients was a landmark intervention, and along with careful management of associated complications, greatly improved the quality of life and minimized mortality.[2] However, a small proportion of patients continued to have proteinuria despite exposure to corticosteroids and carried an unfavorable prognosis. An important contribution toward understanding the profile of nephrotic syndrome was made by the International Study of Kidney Disease in Children (ISKDC) Group, which defined the histological features and the response to corticosteroid therapy.[3] Renal biopsy identified minimal lesions in around 75% of patients, who responded to prednisolone with rapid abolition of proteinuria (steroid sensitive nephrotic syndrome). Although the course of the illness was punctuated with relapses, most of these children eventually attained permanent cure. Four different forms of histological abnormalities were seen in those who had persistent proteinuria (steroid resistant nephrotic syndrome, SRNS),[3] and the outcome was unfavorable in such cases. Similar observations were made in reports from other countries.[4] Corticosteroids, and later cyclophosphamide, were the only specific agents available for treatment for several years, until the introduction of calcineurin inhibitors (cyclosporine, tacrolimus), mycophenolate mofetil, and more recently rituximab.


  Corticosteroid (Prednisone, Prednisolone) Therapy Top


The ISKDC regimen for treating the initial episode in all patients consisted of prednisone 60 mg/m2 per day in divided doses for 4 weeks, and thereafter 40 mg/m2 given as a single dose on 3 consecutive days per week for the next for 4 weeks, and then discontinued (standard 8-weeks treatment). That dosage schedule was decided upon by approval from the participating centers from USA, Mexico, Europe, and Japan. The initial and long-term response to that Schedule, including remission (SSNS) and resistance (SRNS), and the subsequent course in the former (infrequent relapses, frequent relapses, and steroid dependence), were described.[3] For several years, various centers employed the same dosage of prednisolone, administering every alternate day rather than 3 consecutive days/week. In 1993, a multicenter study from Germany reported that the initial administration of prednisolone in a daily dose for 6 weeks and subsequently on alternate days for 6 weeks was superior to the standard treatment.[5] These observations were further confirmed by other workers, and in recent years, the 6-weeks daily and 6-weeks on alternate days regimen has been the standard recommendation. A majority of patients develop relapse of heavy proteinuria after stoppage of the initial prednisolone therapy, which has been defined as being infrequent, frequent, and steroid dependent. Various medications have been used to manage such cases. A small proportion of patients who do not show remission with corticosteroids (SRNS), and occasionally after having shown initial response, present difficult problems and require therapy with medications that carry significant hazards. The management of children with nephrotic syndrome over long periods is associated with complications that require preventive care and appropriate interventions.


  Indian Society of Pediatric Nephrology Guidelines for Management of Nephrotic Syndrome Top


Realizing the need for clear guidelines for the management of nephrotic syndrome, ISPN has presented clear recommendations addressing various aspects of specific treatment and associated problems and complications.[6],[7] The usage of corticosteroids and specific medications is based on critical examination of available evidence and published investigations. The reports mention the process of evaluating the evidence and grading their quality, which are essential for making the recommendations, which would be subject to scrutiny. Various aspects of management are clearly discussed and both reports are extensively referenced.


  Steroid Sensitive Nephrotic Syndrome Top


Treatment of the initial episode

Although prednisolone has been used to manage the initial episode of the nephrotic syndrome, the dosage schedule remains the subject of controversy.[6] Recent investigations suggest that the standard 8-week regimen is not inferior to the longer 6-week + 6-week therapy.[8] However, the ISPN experts after incisive evaluation of various studies conclude that the evidence was insufficient to alter their existing recommendation of the 6-week + 6-week regimen. There are questions whether prednisolone should be stopped at the end of 6-week alternate-day administration or gradually tapered off over the next 8–12 weeks. While few observational studies report benefit of prolonged treatment, convincing evidence of its benefit is not available and ISPN recommends that prednisolone should be discontinued at the end 6-week alternate-day administration.

Management of subsequent course

The ISPN guidelines give clear recommendations for the management of patients with frequent relapses and steroid dependence, and the usage of medications that include levamisole, cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors, and rituximab. Whereas individual centers could modify their usage, depending on several considerations, the guidelines reflect overall consensus and it would be prudent to follow them.

General considerations

Nephrotic syndrome is a long-term disorder in most children and most careful management is required to ensure optimal results. Morbidity must be avoided and normal growth and appropriate quality of life ensured. ISPN recommendations include management of edema, hypovolemia, prevention and treatment of various infections, immunizations, and minimization of drug toxicity. Explanation of the disorder, expected outcome, and emotional support to the family are crucial as parental cooperation is crucial for adequate care of the child.


  Steroid Resistant Nephrotic Syndrome Top


About 10%–15% children with idiopathic nephrotic syndrome do not achieve complete resolution of proteinuria with adequate prednisolone therapy (SRNS). ISPN guidelines for the management of SRNS were initially published in 2009. A substantial amount of information has been available since then, leading to scrutiny of new evidence and making fresh recommendations.[7] The definitions related to steroid resistance, initial as well as later during the course of the disease, are given. All patients with SRNS should undergo a kidney biopsy and expert histological review. Indications for genetic studies and their influence on the management, including renal transplantation, are discussed. The cost of such studies precludes their application in all patients with SRNS, but they should be carried out in patients in whom there is a high probability of detecting abnormalities.

Specific treatment

The report gives recommendations about the use of various medications, their limitations, and toxicity. These are largely similar to those made by the International Pediatric Nephrology Association.[9] Individual centers may modify their usage depending on local factors. Attempt should be made to reduce the severity of proteinuria with addition of angiotensin-converting enzyme inhibitors. Children with SRNS need to be managed by pediatric nephrologists since extreme care is necessary for optimal usage of the hazardous medications.

Supportive care and management of complications in nephrotic syndrome

Edema is the most obvious abnormality in children with nephrotic syndrome. Older texts include bloated pictures of children when effective diuretic agents were not available. The child often has anasarca at the initial presentation, but thereafter significant edema can be avoided. The report gives directions for the treatment of edema with judicious use of various agents. Several other complications including various infections, thrombotic episodes, fluid loss, and hypovolemia need to be recognized early and promptly treated. Height and weight of the patients should be monitored and obesity avoided.

In SRNS with persistent heavy proteinuria, dyslipidemia, hypertension, and other cardiovascular problems and mineral bone abnormalities are frequently observed. Guidelines have been provided for their recognition and management. A significant proportion of patients with SRNS has increasing renal damage and might require kidney support therapy. Renal transplantation should be considered in such cases, which involves several family and economic issues.


  Future Research Top


During recent years, impressive knowledge has been obtained regarding the mechanisms of proteinuria and the critical role of podocytes in maintaining the integrity of filtration barrier.[10] However, what initiates massive proteinuria in the minimal lesion and SRNS remains a mystery. Search for a circulating factor and immunological abnormalities that may be causative, and resolve during complete recovery in these cases, has not been successful. The optimal regimens of corticosteroid and other drugs, especially rituximab, are controversial. SSNS may need to be treated differently in children between 1 and 3 years, when it is often difficult to manage. Well-designed and meticulously executed multicenter studies in South Asia and other countries are needed to address various therapeutic options. Several genetic abnormalities have been identified in SRNS and congenital nephrotic syndrome and their presence in our populations need to be examined. The search for the mechanisms that initiate proteinuria and cause its eventual resolution must continue.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Barness LA, Moll GH, Janeway CA. Nephrotic syndrome. I. Natural history of the disease. Pediatrics 1949;5:486-503.  Back to cited text no. 1
    
2.
Arneil GC. Treatment of nephrosis with prednisolone. Lancet 1956;270:409-11.  Back to cited text no. 2
    
3.
Churg J, Habib R, White RH. Pathology of the nephrotic syndrome in children: A report for the International Study of Kidney Disease in Children. Lancet 1970;760:1299-302.  Back to cited text no. 3
    
4.
Srivastava RN, Mayekar G, Anand R, Choudhry VP, Ghai OP, Tandon HD. Nephrotic syndrome in Indian children. Arch Dis Child 1975;50:626-30.  Back to cited text no. 4
    
5.
Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Eur J Pediatr 1993;152:357-61.  Back to cited text no. 5
    
6.
Sinha A, Bagga A, Banerjee S, Mishra K, Mehta A, Agarwal I, et al. Steroid sensitive nephrotic syndrome: Revised guidelines. Indian Pediatr 2021;58:461-81.  Back to cited text no. 6
    
7.
Vasudevan A, Thergaonkar R, Mantan M, Sharma J, Khandelwal P, Hari P, et al. Consensus guidelines on management of steroid-resistant nephrotic syndrome. Indian Pediatr 2021;58:650-66.  Back to cited text no. 7
    
8.
Webb NJ, Woolley RL, Lambe T, Frew E, Brettell EA, Barsoum EN, et al. Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: Phase III randomised controlled trial and economic evaluation. BMJ 2019;365:l1800.  Back to cited text no. 8
    
9.
Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2020;35:1529-61.  Back to cited text no. 9
    
10.
Benzing T, Salant D. Insights into glomerular filtration and albuminuria. N Engl J Med 2021;384:1437-46.  Back to cited text no. 10
    




 

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Background
Corticosteroid (...
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