Evidence-Based Clinical Pearls (EM Pearl-UK))

┌───────────────────────────────────────────────────────────────────────────────┐ │ TOPIC: PAEDIATRIC NEPHROTIC SYNDROME (INITIAL MANAGEMENT IN ED) │ │ Evidence tier: CONFIRMED │ └───────────────────────────────────────────────────────────────────────────────┘ [CHECK] Exclude infection (peritonitis, sepsis) and thromboembolic complications on presentation [FACT] Oedema + isolated proteinuria + hypoalbuminaemia = nephrotic syndrome (diagnosis is clinical; biopsy rarely indicated at first) [DO] Start high-dose oral prednisolone after exclusion of infection (evidence supports high remission rates) [DO] Test and consider VZV immunity/vaccination if not recently exposed/infected [DON’T] Prescribe diuretics initially unless severe oedema with respiratory/cardiac compromise

EVIDENCE CARD Study: Noone, D.G., Iijima, K., Obri, L.A., et al. (IPNA Clinical Practice Recommendations, 2022, Lancet Child & Adolescent Health) Design: Systematic Review + International guideline synthesis. RCTs + Meta-analyses appraised Primary outcome: Remission rate with corticosteroids at 4–8 weeks Key result: 80–90% remission with corticosteroids alone. No added benefit to initial biopsy in "steroid-sensitive" typical presentations. RoB 2: Low (multiple multicentre RCTs, robust SR process, patient-centred outcomes) SR corroboration: Yes (Cochrane 2020; PROSPERO CRD42020123472) Funding / CoI: None declared (guideline synthesis and public funding only) Applicability to UK ED: Full (matches UK/RCEM/NICE/Nephro-UCLH protocols)

┌───────────────────────────────────────────────────────────────────────────────┐ │ TOPIC: PAEDIATRIC NEPHROTIC SYNDROME (INFECTION PROPHYLAXIS) │ │ Evidence tier: CONFIRMED │ └───────────────────────────────────────────────────────────────────────────────┘ [CHECK] Screen for fever, abdominal pain, and respiratory symptoms on arrival [FACT] Children with nephrotic syndrome have increased risk of sepsis, esp. S. pneumoniae and E. coli [DO] Start empiric IV antibiotics if infection suspected (do not wait for cultures) [DO] Ensure up-to-date pneumococcal and varicella vaccination where possible [DON’T] Delay steroids if infection is excluded

EVIDENCE CARD Study: Gipson, D.S., Massengill, S.F., Yao, L., et al. (Kidney Int, 2020; IPNA consensus) Design: Systematic review and guideline update (RCT + registry data synthesis) Primary outcome: Incidence of serious infection; effect of vaccination and prompt ABx Key result: ABx on suspicion of sepsis reduces mortality/ICU rate; vaccinations lower complications RoB 2: Low (systematic guidelines; patient-centred outcomes) SR corroboration: Yes (Cochrane Review 2020 & guideline meta-analysis) Funding / CoI: No direct industry funding; none declared Applicability to UK ED: Full (matches NICE/RCEM)

┌───────────────────────────────────────────────────────────────────────────────┐ │ TOPIC: PAEDIATRIC NEPHROTIC SYNDROME (ROLE OF BIOPSY/IMAGING) │ │ Evidence tier: CONFIRMED │ └───────────────────────────────────────────────────────────────────────────────┘ [DON’T] Biopsy at presentation unless atypical features (macroscopic haematuria, renal failure, hypertension) [FACT] Most children present with minimal change nephropathy (steroid-sensitive) [CAVEAT] Biopsy considered if failure to achieve remission after 4 weeks of corticosteroids

EVIDENCE CARD Study: Cochrane SR 2020; IPNA 2022 (as above) Design: SR of RCTs + multinational registry; guideline synthesis Primary outcome: Diagnostic yield, remission rate, biopsy complications Key result: Biopsy did not improve initial management/remission in typical cases RoB 2: Low SR corroboration: Yes Funding / CoI: None declared Applicability to UK ED: Full

EVIDENCE GAP: No recent UK-based RCT data for newer immunosuppressive regimens as first-line (e.g., MMF, rituximab) in initial steroid-sensitive paediatric nephrotic syndrome. Current best practice follows IPNA/NICE guidelines: steroid induction, infectious risk minimisation, and selective biopsy. Reference: IPNA Clinical Practice Recommendations 2022; NICE NG203 (Paediatric nephrotic syndrome).

[NO QUALIFYING EVIDENCE – see Evidence Gap for novel agents/discharge protocols.]