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AGN
- 2. GLOMERULUS
- 3. Glomerular disease includes glomerulonephritis, i.e. inflammation of the glomeruli and glomerulopathies when there is no evidence of inflammation. Glomerulonephritis is a subset of glomerulopathies
- 5. Acute glomerulonephritis (AGN) is an abrupt onset of one or more features of an Acute Nephritic Syndrome : • Oedema e.g. facial puffiness • Microscopic / macroscopic haematuria • Decreased urine output (oliguria) • Hyprtension • Azotemia Acute Glomerulonephritis
- 6. Presenting features of AGN Acute nephritic syndrome (most common) Nephrotic syndrome Rapidly progressive glomerulonepritis Hypertensive encephalopathy Pulmonary oedema Subclinical (detected on routine examination)
- 7. Causes of Acute Nephritis Post streptococcal AGN Post-infectious acute glomerulonephritis (other than Grp A B-Haemolytic Stretococci) Subacute bacterial endocarditis Henoch- Schoelein Purpura IgA nephropathy Hereditary nephritis SLE Systemic vasculitis
- 8. Lupus
- 9. In children, the commonest cause of acute nephritic syndrome is post-infectious AGN, mainly due to post-streptococcal infection of the pharynx or skin. Post streptococcal AGN is commonest at 6-10 years age.
- 11. Definition AGN that follows an infection with a nephritogenic strain of group A beta hemolytic streptococci. The classic example of the acute nephritic syndrome. Nelson Textbook of Pediatrics, 7th Edition
- 12. Streptococcal infection of the throat ( strep throat) or skin ( impetigo)
- 13. EpidEmiology 121 of the 124 patients had poststreptococcal nephritis. Department of Pediatrics, HUSM, July 1987- June 1988 Globally - incidence has decreased in the past three decades. Most commonly – sporadic. Despite that, epidemics and clusters of cases - in some poor or rural communities © 2008 American Society of Nephrology Peak incidence - age 5-12 y/o, uncommon <3y/o. Male : female ratio is 2 : 1. (Nelson Textbook of Pediatrics, 7th Edition)
- 14. Etiology and pathogEnEsis The child gets throat or skin infection by nephritogenic strain of group A beta hemolytic streptococci - serotype 12 , 4 and 1 Antibodies to streptoccocus (eg antistreptolysin O) are formed in the circulation Antigen-antibody circulating immune complexes are subsequently deposited along the glomerular basement membrane (GBM).
- 15. Streptococcal infection immune complex formation + deposited in GBM complement system activated immune injuries cellular proliferation GBM fracture capillary lumen narrowed hematuria glomerular blood flow decreased proteinuria oliguria GFR↓ distal sodium reabsorption retention of water & sodium blood volume ↑ edema hypertension Low serum complement
- 17. typical manifEstation Develop acute nephritic syndrome 1–2 wk after an antecedent streptococcal pharyngitis or 3–6 wk after a streptococcal pyoderma. 1.Edema 75% of the patients Face, periorbital area lower extremities generalized (ascites, pleural effusions) 2. Proteinuria – usually normalize after 4 weeks 3. Oliguria school child < 400ml/day preschool child < 300ml/day infant & toddler < 200ml/day
- 18. typical manifEstation 3. Gross hematuria (65% of patients) Smoky, tea-colored, cola-colored, or fresh bloody urine Microscopical hematuria (almost all patients) The urine appears normal, but >3 RBCs/HP are found in centrifuged urine sediment examined microscopically. 4. Hypertension (50%) – mild to moderate, typically subsides promptly after diuresis 5. Nonspecific symptoms: Such as anorexia, vomiting, general malaise, lethargy, abdominal or flank pain, low-grade fever and weight gain.
- 20. Clinical course Spontaneous improvement typically begins within 1 wk with resolution of edema in 5-10 days and hypertension in 2-3 wk, but urinalysis may be abnormal (persistent microscopic hematuria) for a year.
- 21. invEstigations Urinalysis and culture • Haematuria – present in all patients. • Proteinuria (trace to 2+, but may be in the nephrotic range; usually associated with more severe disease.) • Red blood cell casts (pathognomonic of acute glomerulonephritis). • Other cellular casts. • Pyuria may also be present.
- 22. invEstigations Bacteriological and serological evidence of antecedent streptococcal infection: • Raised ASOT ( > 200 IU/ml ). • Increased anti-DNAse B (if available) – a better serological marker of preceding streptococcal skin infection. • Throat swab or skin swab. Renal function test • The BUN concentration is elevated in 75% of patients, and serum creatinine level is increased in one half of the patients, but profound decrease in GFR is uncommon in children. • Hyperkalemia, hypocalcaemia, hyponatremia, and metabolic acidosis are seen only in severe patients.
- 23. InvestIgatIons Full blood count • A mild normochromic anemia may be present from hemodilution and low-grade hemolysis. • Leucocytosis may be present. Complement levels • C3 level – low at onset of symptoms, normalizes by 6wks • C4 is usually within normal limits in post-streptococcal AGN. Ultrasound of the kidneys • Not necessary if patient has clear cut acute nephritic syndrome.
- 24. IndIcatIons for renal BIopsy Severe acute renal failure requiring dialysis. Features suggesting non post-infectious AGN as the cause of acute nephritis. Delayed resolution • Oliguria > 2 weeks • Azotaemia > 3 weeks • Gross haematuria > 3 weeks • Persistent proteinuria > 6 months
- 25. lIght mIcroscope not specIfIc for post streptococcal nephrItIs •Glomeruli appear enlarged and hypercellular. •Diffuse mesangial cell proliferation with an increase in mesangial matrix. •Polymorphonuclear leukocytes are common in glomeruli during the early stage of the disease.
- 26. dIagnosIs Acute onset Symptoms: edema, oliguria, dark urine, hypertension Urinalysis: RBCs, protein, casts Evidences of streptococcal infection: – Prodromes – Elavated serum titers of Abs to streptozymes(ASO) Serum C3 - Reduced
- 29. management Strict monitoring - fluid intake, urine output, daily weight, BP (Nephrotic chart) Penicillin V for 10 days to eliminate β - haemolytic streptococcal infection (give erythromycin if penicillin is contraindicated) Fluid restriction to control oedema and circulatory overload during oliguric phase until child diureses and blood pressure is controlled
- 30. management • Day 1 : up to 400 mls/m²/day. Do not administer intravenous or oral fluids if child has pulmonary oedema. • Day 2 : till patient diureses – 400 mls/m²/day (as long as patient remains in circulatory overload) • When child is in diuresis – free fluid is allowed Diuretic (e.g. Frusemide) should be given in children with pulmonary oedema. It is also usually needed for treatment of hypertension. Diet – no added salt to diet. Protein restriction is unnecessary
- 31. complIcatIons Look out for complications of post- streptococcal AGN: • Hypertensive encephalopathy usually presenting with seizures • Pulmonary oedema (acute left ventricular failure) • Acute renal failure
- 32. management for complIcatIons Significant asymptomatic hypertension symptomatic, severe hypertension or hypertensive emergency / encephalopathy
- 34. Prehypertension is defined as a blood pressure in at least the 90th percentile, but less than the 95th percentile, for age, sex, and height, or a measurement of 120/80 mm Hg or greater. Hypertension is defined as blood pressure in the 95th percentile or greater.
- 36. Acute pulmonary edema MANAGEMENT for coMplicATioNs
- 37. MANAGEMENT for coMplicATioNs Acute Renal Failure
- 38. follow-up For at least 1 year. Monitor BP at every visit Do urinalysis and renal function to evaluate recovery. Repeat C3 levels 6 weeks later if not already normalised by the time of discharge.
- 39. ouTcoME Short term outcome: Excellent, mortality <0.5%. Long term outcome: 1.8% of children develop chronic kidney disease following post streptococcal AGN. These children should be referred to the paediatric nephrologists for further evaluation and management.
- 40. sourcEs Paediatric Protocols 3rd Edition Nelson Textbook of Pediatrics, 7th Edition Renal Unit , Royal Hospital for Sick Children , Yorkhill Division © 2008 American Society of Nephrology
- 41. THANK You
Editor's Notes
- Normal histological structure of a glomerulus. On the right, is a 3-D illustration of a glomerulus. Left one shows AA = affrent arteriole, EA= Efferent arteriole, BC= Bowman’s capsule, US= Urinary space
- There is an overlap between these terms