1. Nephrotic syndrome- -oedematous and oliguric 22 nd June 2012 Rachel Lennon Consultant Paediatric Nephrologist Royal Manchester Childrens Hospital

2. Nephrotic syndrome: Most common glomerular disorder in children

3. Endothelial cells Podocyte GBM 1 million glomeruli in each human kidney

4. Glomerular filtration barrier Podocytes Glomerular endothelial cells GBM 180 litres of water and small solutes- almost no proteins Slit diaphragm

5. A clinical syndrome: Triad Massive proteinuria Oedema Albumin <25g/l

6. Congenital – Congenital infections – Genetic mutations Eg. Nephrin, podocin Acquired – No clearly identified mechanism – Association with viral infections – Circulating factors Recurrence of FSGS post renal transplant Materno-fetal transmission Aetiology

7. Minimal change nephrotic syndrome (MCNS): Commonest in children Membranous nephropathy Focal segmental glomerulosclerosis Mesangioproliferative GN

8. Minimal change nephrotic syndrome Electron microscopy

9. Induction and maintenance therapy Glucocorticoids: ISKDC regime – 90% with MCNS initially respond 33% no further relapse 33% infrequent relapse 33% frequent relapse Prophylactic penicillin 2 nd line therapy – Cytotoxics Cyclophosphamide Ciclosporin

10. Complications Thrombosis – Haemoconcentration – Increased fibrinogen, factor VII, X, VIII – Decreased anti-thrombin III and plasminogen Infections – Immunological losses Pneumococcal infections Primary peritonitis

11. Acute management of nephrotic syndrome

12. Case 1 3 year old boy – Facial swelling for 2 weeks – Treated with antihistamines – Urinalysis 3+ protein 1+blood – HR/BP/CRT normal – Periorbital and lower limb oedema – Albumin 15, Urea 4.5 Creat 30, Urine Na 30 Treatment? Prednisolone 60 mg/m 2 /day (Prednos trial?) Penicillin V Daily monitoring until remission

13. Δ Nephrotic syndrome ABC HR/BP/CRT normal Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Oedema Estimate dry weight Diuretics: Furosemide and spironalactone Close monitoring Daily weight Fluid balance Close monitoring Daily weight Fluid balance

14. Case 2 7 year old boy with SSNS – Unwell with D&V for 3 days, – Urine 3+ protein – Lower limb oedema – HR 130, BP 100/78, CRT 5 seconds – Albumin 12, Urea 9.5, Creat 42, Urine Na 10 Treatment? IV fluid bolus (10ml/kg 4.5%HAS) Reassess Urine output Prednisolone 60 mg/m 2 /day Penicillin V Daily monitoring until remission

15. Δ Nephrotic syndrome ABC HR/BP/CRT normal Hypovolaemia Fluid bolus: 10- 20ml/kg 4.5% HAS Reassess Fluid bolus: 10- 20ml/kg 4.5% HAS Reassess Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Oedema Estimate dry weight Diuretics: Furosemide and spironalactone Close monitoring Daily weight Fluid balance Close monitoring Daily weight Fluid balance Urine Na Haematocrit Urine Na Haematocrit

16. Case 3 5 year old girl with FRNS – Ciclosporin – Oedematous for 2-3 weeks – Symptomatic oedema – HR 120, BP 105/80, CRT <2s – Albumin 8, Ur 7.5, Creat 52, Urine Na 15 Treatment? Cautious use of 20% albumin (2.5-5ml/kg dry weight) over 4 hours with IV furosemide at 2 hours. Risk of life threatening pulmonary oedema Daily 20% albumin Prednisolone 60 mg/m 2 /day Penicillin V Daily monitoring until remission

17. Δ Nephrotic syndrome ABC HR/BP/CRT normal Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Oedema Symptomatic oedema 0.5-1g/kg (0.25-5ml/kg) 20% salt poor albumin Over 4 hours Furosemide (1mg/kg) at 2 hours In consultation with Paediatric Nephrologist 0.5-1g/kg (0.25-5ml/kg) 20% salt poor albumin Over 4 hours Furosemide (1mg/kg) at 2 hours In consultation with Paediatric Nephrologist Estimate dry weight Diuretics: Furosemide and spironalactone Close monitoring Daily weight Fluid balance Close monitoring Daily weight Fluid balance Urine Na Haematocrit Urine Na Haematocrit

18. 3.5g/kg 4hrs 2.5g/kg 3hrs no diuretic 1g/kg over 1 hour ISKDC- mortality in MCNS

19. Δ Nephrotic syndrome ABC HR/BP/CRT normal Hypovolaemia Fluid bolus: 10- 20ml/kg 4.5% HAS Reassess Fluid bolus: 10- 20ml/kg 4.5% HAS Reassess Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Predinsolone 60mg/m 2 /day Fluid restriction to 70% Low salt diet Oedema Symptomatic oedema 0.5-1g/kg (0.25-5ml/kg) 20% salt poor albumin Over 4 hours Furosemide (1mg/kg) at 2 hours In consultation with Paediatric Nephrologist 0.5-1g/kg (0.25-5ml/kg) 20% salt poor albumin Over 4 hours Furosemide (1mg/kg) at 2 hours In consultation with Paediatric Nephrologist Estimate dry weight Diuretics: Furosemide and spironalactone Close monitoring Daily weight Fluid balance Close monitoring Daily weight Fluid balance Urine Na Haematocrit Urine Na Haematocrit

20. Questions?