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Post-infectious glomerulonephritis

Post-infectious glomerulonephritis

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Post-infectious glomerulonephritis

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  1. Post-infectious glomerulonephritis Stephen Marks Consultant Paediatric Nephrologist Great Ormond Street Hospital for Children and UCL Institute of Child Health, London, UK. Nephrology for the General Paediatrician, Manchester Friday 22 June 2012

  2. Summary • Case presentation • Causes • Management • Prognosis

  3. Case presentation • 15-year old Afro-Caribbean boy • 1 week history of abdominal, leg and facial swelling with increasing shortness of breath • he and his siblings have had a few ?viral infections with sore throat over the last 3 winter months • no rash but reduced oral intake over last 24 hours with oliguria • On examination • unwell with weight on 25th centile and height on 2nd centile • capillary refill time of 2 seconds with palpable peripheral pulses • prominent apex beat, BP = 152/94 mmHg • tachypnoeic with lung crepitations in all areas • generalised oedema and ascites

  4. Hb 12.0 g/dl WCC 12.3 x 109/l Platelets 325 x 109/l Sickle screen -ve Sodium 130 mmol/l Potassium 7.2 mmol/l Chloride 108 mmol/l tCO2 14 mmol/l Urea 24.8 mmol/l Creatinine 258 µmol/l Calcium 1.8mmol/l Albumin 24g/l Phosphate 1.6 mmol/l ALP 160 U/l ALT 24 U/l Bilirubin 12 µmol/l Urinary dipstick proteinuria ++++ haematuria ++ CXR normal heart size pulmonary oedema Renal ultrasound two big echobright kidneys Investigations

  5. Question (a) • Which two of the following are the best descriptions of his clinical condition ? A. Acute renal failure / acute kidney injury B. Acute on chronic renal failure C. Chronic renal failure or chronic kidney disease D. End-stage renal failure E. Neither nephritic nor nephrotic syndrome F. Nephritic syndrome (but not nephrotic syndrome) G. Nephrotic syndrome (but not nephritic syndrome) H. Nephritic and nephrotic syndrome

  6. Question (b) • In which range is this patient’s corrected calcium in ? A. 1.71 - 1.8mmol/l B. 1.81 - 1.9mmol/l C. 1.91 - 2.0mmol/l D. 2.01 - 2.1mmol/l E. 2.11 - 2.2mmol/l

  7. Question (c) • Which of the following would not be part of an effective management plan for his hyperkalaemia ? • Calcium carbonate • Calcium gluconate • Calcium resonium • Cardiac monitor • Furosemide • Insulin and dextrose infusion • Salbutamol • Sodium bicarbonate

  8. Question (d) • How would you treat his hypertension ? • Intravenous 4.5% albumin infusion • Intravenous 20% albumin infusion and furosemide • Intravenous furosemide • Intravenous labetalol • Low salt diet • Oral amlodipine • Oral atenolol • Oral enalapril • Oral furosemide • Oral nifedipine

  9. Question (e) • Despite initial fluid and medical management, he becomes anuric for 48 hours and his plasma creatinine increases to 512µmol/l • What one investigation would you do to help make the diagnosis ? • ANA and anti-dsDNA • Anti-GBM antibody • Anti-streptolysin O and anti-DNAase B titres • Auto-immune screen • Blood film • C3, C4 and auto-antibody screen • Immunoglobulin levels • Renal biopsy

  10. Question (f) • What is the most likely diagnosis ? • Haemolytic uraemic syndrome • Minimal change nephrotic syndrome • Post-infectious glomerulonephritis • Renal venous thrombosis • Sickle nephropathy

  11. Question (a) • Which two of the following are the best descriptions of his clinical condition ? A. Acute renal failure / acute kidney injury B. Acute on chronic renal failure C. Chronic renal failure or chronic kidney disease D. End-stage renal failure E. Neither nephritic nor nephrotic syndrome F. Nephritic syndrome (but not nephrotic syndrome) G. Nephrotic syndrome (but not nephritic syndrome) H. Nephritic and nephrotic syndrome

  12. Question (a) • Which two of the following are the best descriptions of his clinical condition ? A. Acute renal failure / acute kidney injury B. Acute on chronic renal failure C. Chronic renal failure or chronic kidney disease D. End-stage renal failure E. Neither nephritic nor nephrotic syndrome F. Nephritic syndrome (but not nephrotic syndrome) G. Nephrotic syndrome (but not nephritic syndrome) H. Nephritic and nephrotic syndrome

  13. Question (b) • In which range is this patient’s corrected calcium in ? A. 1.71 - 1.8mmol/l B. 1.81 - 1.9mmol/l C. 1.91 - 2.0mmol/l D. 2.01 - 2.1mmol/l E. 2.11 - 2.2mmol/l

  14. Question (b) • In which range is this patient’s corrected calcium in ? A. 1.71 - 1.8mmol/l B. 1.81 - 1.9mmol/l C. 1.91 - 2.0mmol/l D. 2.01 - 2.1mmol/l E. 2.11 - 2.2mmol/l

  15. Corrected calcium • How do you calculate corrected calcium from total calcium result ? • Corrected calcium = Total calcium + [(40 - Patient’s albumin (g/l)) x 0.025] • Some sources use correction factor of 0.02 instead of 0.025

  16. Corrected calcium • Corrected calcium = Total calcium + [(40 - Patient’s albumin (g/l)) x 0.025] • For this case, corrected calcium = 1.8mmol/l + [(40 - 24) x 0.025] = 1.8mmol/l + (16 x 0.025) = 1.8mmol/l + 0.4 = 2.2mmol/l

  17. Question (c) • Which of the following would not be part of an effective management plan for his hyperkalaemia ? • Calcium carbonate • Calcium gluconate • Calcium resonium • Cardiac monitor • Furosemide • Insulin and dextrose infusion • Salbutamol • Sodium bicarbonate

  18. Question (c) • Which of the following would not be part of an effective management plan for his hyperkalaemia ? • Calcium carbonate • Calcium gluconate • Calcium resonium • Cardiac monitor • Furosemide • Insulin and dextrose infusion • Salbutamol • Sodium bicarbonate

  19. Question (d) • How would you treat his hypertension ? • Intravenous 4.5% albumin infusion • Intravenous 20% albumin infusion and furosemide • Intravenous furosemide • Intravenous labetalol • Low salt diet • Oral amlodipine • Oral atenolol • Oral enalapril • Oral furosemide • Oral nifedipine

  20. Question (d) • How would you treat his hypertension ? • Intravenous 4.5% albumin infusion • Intravenous 20% albumin infusion and furosemide • Intravenous furosemide • Intravenous labetalol • Low salt diet • Oral amlodipine • Oral atenolol • Oral enalapril • Oral furosemide • Oral nifedipine

  21. Question (e) • Despite initial fluid and medical management, he becomes anuric for 48 hours and his plasma creatinine increases to 512µmol/l • What one investigation would you do to help make the diagnosis ? • ANA and anti-dsDNA • Anti-GBM antibody • Anti-streptolysin O and anti-DNAase B titres • Auto-immune screen • Blood film • C3, C4 and auto-antibody screen • Immunoglobulin levels • Renal biopsy

  22. Question (e) • Despite initial fluid and medical management, he becomes anuric for 48 hours and his plasma creatinine increases to 512µmol/l • What one investigation would you do to help make the diagnosis ? • ANA and anti-dsDNA • Anti-GBM antibody • Anti-streptolysin O and anti-DNAase B titres • Auto-immune screen • Blood film • C3, C4 and auto-antibody screen • Immunoglobulin levels • Renal biopsy

  23. Question (f) • What is the most likely diagnosis ? • Haemolytic uraemic syndrome • Minimal change nephrotic syndrome • Post-infectious glomerulonephritis • Renal venous thrombosis • Sickle nephropathy

  24. Question (f) • What is the most likely diagnosis ? • Haemolytic uraemic syndrome • Minimal change nephrotic syndrome • Post-infectious glomerulonephritis • Renal venous thrombosis • Sickle nephropathy

  25. Hypocomplementaemia • Immune-complex mediated disorders • infective endocarditis • shunt nephritis • activation of the complement pathway and resulting hypocomplementaemia • MPGN (but not FSGS) associated with low C3 • RPGN is a clinical diagnosis and is not necessarily hypocomplementaemic

  26. Post-infectious glomerulonephritis - 1 • Post-streptococcal GN • prototype for bacterial infection-related GN (PIGN) with antecedent pharyngeal (7 - 15 days) or cutaneous infection (eg. impetigo; 4 -6 weeks) • caused by nephritogenic strain of Streptococci • NATURE OF NEPHRITOGENIC ANTIGEN DEBATED • <50% complete remission on long follow-up of immunocompromised adults with atypical PIGN • Moroni G, Ponticelli C (2009)

  27. Post-infectious glomerulonephritis - 2 • Incidence and spectrum changing • epidemic form declined in industrialised countries • post-streptococcal glomerulonephritis = 28 - 47% of acute GN • Staph aureus / epidermidis = 12 - 24% • Gram negative bacteria = 10 - 22% • others • inc. bacterial endocarditis, shunt infections, atypical PIGN • acute endocapillary glomerulonephritis with mesangial and capillary granular immune deposition • Montseny JJ et al (1995) Medicine (Baltimore) • Moroni G et al (2002) Nephrol Dial Transplant • Nasr SH et al (2008) Medicine (Baltimore)

  28. Percutaneous renal biopsy

  29. Clinical course of PIGN • Acute GN < 2 weeks • Massive proteinuria in <4% of PSGN children • Severe end of spectrum with RPGN • histopathologically crescentic GN • Resolution of hypocomplementaemia (C3) • by 8 - 10 weeks

  30. Post-infectious glomerulonephritis • The indications for renal biopsy are • severe renal dysfunction at presentation • rapidly progressive acute renal failure • atypical presentation • delayed recovery • macroscopic haematuria for >1 month • low C3 levels for >6 months • heavy proteinuria for > 6 months • Note that microscopic haematuria can persist for years following the acute episode

  31. Causes of PIGN

  32. Treatment of PIGN • Supportive treatment • management of fluids and electrolytes • acute (and chronic) treatment of hypertension, oedema, congestive cardiac failure and proteinuria • Specific treatment • antibiotics are unhelpful for reversing GN as established glomerular lesions induced by immune complexes • penicillin (or erythromycin if allergic) • to resolve well-documented streptococcal infection • to prevent spread of nephritogenic streptococcus in contacts • no RCT but intravenous methylprednisolone if extensive glomerular crescents and RPGN • based on extrapoloation from other causes of RPGN

  33. Nephritic syndrome Nephrotic syndrome Mixed nephritic and nephrotic

  34. Nephritic syndrome Haematuria Proteinuria Oliguria Hypertension Nephrotic syndrome Mixed nephritic and nephrotic

  35. Nephritic syndrome Haematuria Proteinuria Oliguria Hypertension Nephrotic syndrome Proteinuria > 40mg/m2/hour > 1g/m2/day Hypoalbuminaemia < 25g/l Oedema (Hyperlipidaemia) Mixed nephritic and nephrotic

  36. Nephritic syndrome Commonest cause PIGN / PSGN or post-infectious glomerulonephritis Nephrotic syndrome Commonest cause MCD / MCNS or minimal change nephrotic syndrome Mixed nephritic and nephrotic

  37. Nephritic syndrome Commonest cause PIGN / PSGN or post-infectious glomerulonephritis Nephrotic syndrome Commonest cause MCD / MCNS or minimal change nephrotic syndrome Mixed nephritic and nephrotic Commonest cause of mixed nephritic and nephrotic syndrome is post-infectious GN

  38. Red blood cell cast

  39. Prerenal • Renal • Postrenal

  40. Clinical features - Examination • State of patient • Routine observations • temperature, HR, SBP, RR, SaO2, AVPU (GCS) • core-peripheral temperature • Serial plot of weights, heights and OFC • State of hydration • peripheral perfusion, JVP, oedema • Signs of cardiac failure • Clinical clues of multi-system disease • rash, arthropathy, arthritis, oral lesions • Palpable kidneys or bladder or masses

  41. Investigations – Blood tests (1) • Full blood count, blood film and ESR • Coagulation screen • Cross-match • Serum electrolytes • U&Es, Cl, CO2, urea, creatinine, glucose • LFTs, CK, urate, bone profile • Ca, Mg, PO4, ALP, albumin • Blood culture and CRP

  42. Investigations – Blood tests (2) • Complement assays • C3, C4 and C3 nephritic factor • Immunoglobulins including IgA • ASOT and antiDNAase B • ANA, dsDNA, qDNA, ENA, ANCA, ACIgM/G • Autoimmune profile and anti-GBM Ab

  43. Investigations – Urine tests • Urinalysis • Urine M,C&S • Urine electrolytes • Fractional excretion of sodium (FENa) = UNa x PCr————— PNa x UCr

  44. Urine electrolytes in ARF • Only on patients NOT on diuretics Test Prerenal Renal Na <20 >20 Urea >250 <150 U:P urea >20 <10 U:P Cr >20 <15 Sediment Nil ? Sediment

  45. Investigations – Other tests • Renal ultrasound scan • bilateral echogenic kidneys • Percutaneous renal biopsy • confirm PIGN • exclude MPGN • consider crescentic GN

  46. Investigations – Ongoing tests • U&Es, CO2 and creatinine • frequency determined by clinical picture and may be appropriate to perform up to every 6 hours • Ca, PO4, Mg, albumin, ALP (at least daily) • FBC daily • Urinalysis daily • Urine electrolytes daily (unless on diuretics)

  47. Fluid balance

  48. Patient Progress - 1 • Further fluid boluses of crystalloid or colloid +/- furosemide as indicated by clinical state of hydration and urine output • Monitoring • daily or twice daily weights • accurate input-output recording • at least 4 hourly BP • at least 4 hourly monitoring of peripheral-core temperature gradient

  49. Patient Progress - 2 • Ongoing fluid management • initially simplest plan is to give insensible losses (400 ml/m2/day or 30 ml/kg/day) and replace UO • GIVE 100% URINE OUTPUT (UO) IF EUVOLAEMIC • RESTRICT TO 50-75% UO IF OVERLOADED • MODIFIED TO FLUID RESTRICTION IF ON DIALYSIS OR URINE OUTPUT ESTABLISHED • In polyuric recovery phase • replace urine output with insensible losses for 24 hours, then set fluid target if renal function continuing to improve

  50. Multidisciplinary team • Doctors • Nurses • Pharmacists • Dietitians • Play therapists • Social worker • Psychosocial team