Summary
PREDNOS 2 was a double blind placebo controlled trial done to investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection—related relapses. It evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. At the beginning of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. The primary outcome was the incidence of first upper respi-ratory tract infection-related relapse. The modified intention-to-treat analysis population comprised 271 children (mean (SD) age, 7.6 (3.5) years; 64.2% male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) in the predniso-lone arm and 58 (44.3%) in the placebo arm (adjusted risk difference, 0.02; 95% CI, 0.14 to 0.10; P =0.70). No evidence was found that the treatment effect differed according to background immuno-suppressive treatment. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40–1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81–1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P=0.09). The authors concluded that, results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK and further work is needed to study the inter-ethnic differences in the study response.
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Christian MT, Webb NJA, Mehta S, et al. Evaluation of daily low-dose prednisolone during upper respiratory tract infection to prevent relapse in children with relapsing steroid-sensitive nephrotic syndrome: The PREDNOS 2 randomized clinical trial. JAMA Pediatr. 2022; 176:236–43.
Christian MT, Webb NJ, Woolley RL, et al. Daily low-dose prednisolone to prevent relapse of steroid-sensitive nephrotic syndrome in children with an upper respiratory tract infection: PREDNOS2 RCT. Health Technol Assess. 2022; 26:1–94.
Higgins JPT, Savoviæ J, Page MJ, Sterne JAC. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Accessed March 13, 2022. Available: https://drive.google.com/file/d/1Q4Fk3HCuBRwIDWTGZa5oH11OdR4Gbhdo/view
References
Sinha A, Bagga A, Banerjee S, et al. Expert Group of Indian Society of Pediatric Nephrology. Steroid Sensitive Nephrotic Syndrome: Revised Guidelines. Indian Pediatr. 2021; 58: 461–81.
Oh GJ, Waldo A, Paez-Cruz F, et al. Steroid-associated side effects in patients with primary proteinuric kidney disease. Kidney Int Rep. 2019; 4: 1608–16.
Mattoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron. 2000; 85: 343–45.
Abeyagunawardena AS, Trompeter RS. Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial. Arch Dis Child. 2008; 93:226–28.
Gulati A, Sinha A, Sreenivas V, et al. Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011; 6: 63–69.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl. 2012; 2:139–274.
Abeyagunawardena AS, Thalgahagoda RS, Dissanayake PV, et al. Short courses of daily prednisolone during upper respiratory tract infections reduce relapse frequency in childhood nephrotic syndrome. Pediatr Nephrol. 2017; 32: 1377–82.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021; 100(4S): S1–S276.
Christian MT, Webb NJA, Mehta S, et al. Evaluation of daily low-dose prednisolone during upper respiratory tract infection to prevent relapse in children with relapsing steroid-sensitive nephrotic syndrome: The PREDNOS 2 randomized clinical trial. JAMA Pediatr. 2022; 176: 236–43.
Crane C, Bakhoum C, Ingulli E. Rates of idiopathic childhood nephrotic syndrome relapse are lower during the COVID-19 pandemic. Pediatr Nephrol. February: 24, 2022. P.1–7.
References
Chanchlani R, Parekh RS. Ethnic differences in childhood nephrotic syndrome. Front Pediatr. 2016; 4:39.
Hodson EM, Craig JC, Willis NS. Evidence-based manage-ment of steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2005; 20:1523–30.
Sinha A, Bagga A, Banerjee S, et al; Expert Group of Indian Society of Pediatric Nephrology. Steroid Sensitive Nephrotic Syndrome: Revised Guidelines. Indian Pediatr. 2021; 58:461–81.
Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021; 100:753–79.
Alwadhi RK, Mathew JL, Rath B. Clinical profile of children with nephrotic syndrome not on glucorticoid therapy, but presenting with infection. J Paediatr Child Health. 2004; 40:28–32.
Arun S, Bhatnagar S, Menon S, et al. Efficacy of zinc supplements in reducing relapses in steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2009; 24:1583–86.
MacDonald NE, Wolfish N, McLaine P, Phipps P, Rossier E. Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr. 1986;108(3):378–82.
Moorani KN, Khan KMA, Ramzan A. Infections in children with nephrotic syndrome. J Coll Physicians Surg Pak. 2003; 13:337–39.
Yap HK, Cheung W, Murugasu B, et al. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol. 1999; 10:529–37.
Bruneau S, Dantal J. New insights into the pathophysiology of idiopathic nephrotic syndrome. Clin Immunol. 2009;133: 13–21.
Leisti S, Hallman N, Koskimies O, et al. Association of postmedication hypocortisolism with early first relapse of idiopathic nephrotic syndrome. Lancet. 1977; 2:795–96.
Leisti S, Koskimies O, Perheentupa J, et al. Idiopathic nephrotic syndrome: prevention of early relapse. Br Med J. 1978;1(6117):892.
Mattoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron. 2000; 85:343–45.
Abeyagunawardena AS, Trompeter RS. Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomized controlled trial. Arch Dis Child. 2008; 93:226–28.
Gulati A, Sinha A, Sreenivas V, et al. Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011; 6:63–69.
Abeyagunawardena AS, Thalgahagoda RS, Dissanayake PV, et al. Short courses of daily prednisolone during upper respiratory tract infections reduce relapse frequency in childhood nephrotic syndrome. Pediatr Nephrol. 2017;32(8): 1377–82.
Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015 Mar 18;2015(3):CD001533.
Christian MT, Webb NJA, Mehta S, et al. Evaluation of daily low-dose prednisolone during upper respiratory tract infection to prevent relapse in children with relapsing steroid-sensitive nephrotic syndrome: The PREDNOS 2 randomized clinical trial. JAMA Pediatr. 2021: e215189.
Sinha A, Bagga A, Iyengar A, Mathew JL. Is two-month initial prednisolone treatment for nephrotic syndrome inferior to longer duration therapy? Indian Pediatr. 2014; 51:811–17.
Mayer G. Precision medicine in nephrology. Nephrol Dial Transplant. 2021;36(S 2):1–2.
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Mathew, J.L., Bagga, A., Sinha, A. et al. Short Course of Daily Prednisolone During Upper Respiratory Tract Infection for Children With Relapsing Steroid Sensitive Nephrotic Syndrome. Indian Pediatr 59, 312–319 (2022). https://doi.org/10.1007/s13312-022-2499-0
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DOI: https://doi.org/10.1007/s13312-022-2499-0