Acute glomerulonephritis for UGs

Approach to a child with acute glomerulonephritis

1. Acute Glomerulonephritis Dr. CSN Vittal

2. Definition An acute inflammation of renal glomerular parenchyma due to deposition of immune complexes characterized by sudden onset of oliguria, hematuria, hypertension and edema

3. Incidence 2 to 4 % of pediatric admissions in India 90 % of renal disease of childhood

4. Etiology Streptococcal infection Non streptococcal Bacterial : Infective endocarditis, shunt nephritis, typhoid, syphilis, S.pneumoniae , meningococcal Viral : HBV, mumps, varicella, ECHO, coxsackie, measles, infective mononucleosis Autoimmune Goodpastuer’s syndrome, HSP, SLE, IgA nephropathy Miscellaneous GBS, DPT vaccination, Irradiation to Wilms tumor

5. Pathology Gross : - Both kidneys enlarged - Ischemic Microscopy : - Glomeruli enlarged, infiltrated by polymorphs - Epithelial crescents Immunofluorescence : - Lumpy-bumpy deposits of IgG, antigen and C3 Electron microscopy : - Mesangial proliferation and mesangial matrix deposition - Lumps of immune complex depositions on the epithelial side of GBM

6. Electron microscopy , electron-dense deposits, or “humps,” are observed on the epithelial side of the glomerular basement membrane Immunofluorescence microscopy :- pattern of “lumpy-bumpy ” deposits of immunoglobulin and complement on the glomerular basement membrane and in the mesangium .

7. The Clinical Spectrum of Renal Disease Disease Category (Most to Least Severe) Asymptomatic (e.g. Thin basement membrane disease) (Least Severe) Chronic progressive glomerulopathy (e.g. Diabetes nephropathy) Nephrotic syndrome (e.g. Minimal change disease ) Nephritic syndrome (e.g. post-infectious GN) RPGN (Most Severe) Clinical Signs / Symptoms Microscopic hematuria Insidious progressive loss of renal function Greater than 3.5 gm of protein in 24 hr urine Hypertension, RBC casts, Hematuri, Azotemia Acute renal failure + nephritic syndrome

8. AGN - Pathophysiology Oliguria Spasm of afferent arteriole ( i blood flow) Obliteration of lumen by mucosal edema & cellular infiltration Crescents causing obstruction h absorption of Na and water from renal tubules

9. AGN - Pathophysiology Hypertension h absorption of Na and water from renal tubules h sympathetic activity h arterial spasm h cardiac output

10. AGN - Pathophysiology Oedema Retention of Na and water from renal tubules Circulation of unknown antigen causing peripheral vasodilatation

11. AGN - Pathophysiology Hematuria Macroscopic = > 25000 RBC / ml Microscopic = Presence of 5 or > RBC per mm 3 fresh uncentrifuged midstream urine > 5 RBC per hpf in centrifuged specimen (of 10 ml, at 750 rpm for 5 min)

12. Post Streptococcal Glomerulonephritis - Etiology Streptococcal serotypes involved Pharyngitis : Types 1, 3, 4 , 12 , 25, 49 Pyoderma Types 2,47, 49 , 55, 57, 60 Streptococcal antigens involved in immune response : Zymogen precursor of exotoxin Glutaraldehyde phosphate dehydrogenase Usually occurs 7-14 days after pharyngitis and 2 wks – 6 wks after skin infection

13. Post Streptococcal Glomerulonephritis Age group 2 – 12 yrs (Rare before 2 yrs) Sex Male predominance Socioeconomic group Common in low socioeconomic group Seasonal variation During winter and rainy season serotype 12 causes Ac. pharyngitis During summer – serotype 49 causes skin infections

14. Post Streptococcal Glomerulonephritis Pathogenesis Cross-reactivity of streptococcal pyogenic exotoxin (SPE)-B and other M proteins with various components of the glomerular basement membrane. Type III immunological reaction in which glomeruli are damaged due to deposition of IgG antibody , antigen and complement C3 . Rarely C1q and C4 may be involved Nephritis-Associated Plasmin Receptor ( NAPlr )  is involved

15. Post Streptococcal Glomerulonephritis Clinical Features Puffiness of face – more in the mornings Edema feet Oliguria ( < 400 ml / m 2 ) Hematuria (cola coloured urine) Breathlessness due to hypertensive heart failure Fever Hypertension Abdominal pain Atypical presentations: Hypertensive encephalopathy – confusion, convulsions, etc. Pulomonary edema – due to CHF Acute renal failure

16. Hypertension Values Above;- 80 / 45 Preterm 90 / 60 Term Newborn 120 / 75 Up to 2 years 130 / 80 2 – 5 years 135 / 85 6 – 11 years 140 / 90 Older children

17. Post Streptococcal Glomerulonephritis Diagnostic criteria of APSGN At least 2 of the following criteria must be present Positive throat or skin culture for streptococcus – Confirmatory or Carrier state Streptococcal products like anti-streptokinase, anti- hyalironidase , anti- DNAse B, ASO titre are elevated (Anti – DNAse B is the single most specific test for Streptococcal infection) Hypocomplementemia : Serum C3 reduced to 90% and CH50 decreased with in 2 weeks, but C4 is normal. The antistreptolysin O titre is commonly elevated after a pharyngeal infection but rarely increases after streptococcal skin infections.

18. Post Streptococcal Glomerulonephritis Investigations - For kidney injury : Urine analysis Proteinuria – non selective; 1+ or 2+ protein with red cells Hematuria : - Macroscopic: Plenty of RBC & RBC casts in urine - Microscopic: > 5 RBC / HPF in 10 ml centrifuged urine Hypocomplementemia Kidney function Tests Blood urea S. creatinine ( h due to i GFR )

19. Red Cell Cast in urine

20. Diagnosis of Glomerulonephritis Low C3 complement Normal C3 complement Systemic Diseases SLE Infective endocarditis Shunt nephritis Cryoglobulinemia Isolated Renal Diseases Postinfectious nephritis Membranoproliferative GN Systemic Diseases Polyarteritis nodosa Wageners ’ granulomatosis Henoch- Schonlein purpura Goodpasture’s syndrome Isolated Renal Diseases IgA nephropathy RPGN Antineutrophil cytoplasmic antibody (ANCA) immune complex disease

21. Post Streptococcal Glomerulonephritis Course Renal Failure – less than 1 % in children, slightly higher in adults Resolution usually quick, plasma Cr usually returns to previous levels by 3-4 weeks Hematuria resolves usually within 3-6 months, Proteinuria falls at a slower rate Some patients experience htn , recurrent proteinuria, and renal insufficiency 10-40 yrs after > 20% of adults may have some degree of persistent proteinuria and or compromise of GFR for 1 year

22. Post Streptococcal Glomerulonephritis Complications 1 . Hypertensive encephalopathy Failure of autoregulatory system of the vessels of brain due to acute rise of blood pressure Altered sensorium, convulsions, etc , 2. Hypertensive heart failure 3. Hypocalcemia 4. Hyperphosphatemia 5. Hyperkalemia 6. Acute renal failure

23. Post Streptococcal Glomerulonephritis Management Diet / fluids Diuretics Treatment of Hypertension Infections control Management of Lt ventricular failure

24. 01 02 03 04 05 Diuretics Infections control Diet / fluids Tt of Hypertension Management of Complications Post Streptococcal Glomerulonephritis Management

25. Diet / Fluids Intake of sodium, potassium and fluids is restricted until blood levels of creatinine reduce and urine output increases Overhydration may increase the risk of hypertension and precipitate left ventricular failure. Monitor fluid Input and Output. R estriction of fluid intake to an amount equal to insensible losses and 24 hr urine output. Daily weight monitoring 01

26. Diuretics: Treatment of Edema For milder edema : Oral frusemide at a dose of 1-3 mg/kg; For pulmonary edema : IV frusemide (2-4 mg/kg) The edema disappears with the return of renal function 02

27. Treatment of Hypertension Mild cases – Managed with salt & water restriction. Drugs used: Atenelol , hydralazine, nifedipine, Risk of hyperkalemia with ACE inhibitors and beta blocker 03

28. Infections control If active pharyngitis or pyoderma is present Drug of choice: Penicillin 4 – 8 Lakhs PPF for 10 days Treatment with penicillin has no effect on the course of the disease 04

29. Management of complications: Left ventricular failure Hypertensive encephalopathy Acute renal failure Acidosis Hyperkalemia Hyperphosphatemia Hypocalcemia Seizures 05

30. Management of Hypertensive Crisis / Encephalopathy 1. Intravenous Sodium Nitroprusside [Arterial & venous vasodilator] Dose : 0.3 µg / kg / min (max 10 µg / kg / min) 2. Propranalol : [b 1 selective blocker] Dose: 1-3 mg / kg / dose q 12 h 3. Esmolol: [b 1 selective blocker] Dose: 130 – 300 µg / kg / min 4. Nifidepine : (Calcium channel blocker) Dose : 0.5 mg / kg Sublingual repeated after 30 min 5. Amlodepine : (Calcium channel blocker) Dose : 0.1 to 0.6 mg / kg / d in 2-3 doses – Oral 6. Labetelol : [Combined b -adrenergic (b1 & b2) and a-adrenergic blocker] Dose : 0.2-1.0 mg/kg can be given as an IV bolus every 10 min; Dosages of 0.25 - 3 mg / kg / hr by IV infusion.. 7. Hydralazine: [Direct arterial vasodilator with no effect on venous circulation] Dose : 0.1 - 0.2 mg / kg every 2 hrs (max 10 µg / kg / min)

31. Indications for Renal Biopsy 1 Features of systemic illness: features. Fever, rash, joint pain, heart disease 2 Severe renal failure requiring dialysis 3 Mixed features of glomerulonephritis & nephrotic syndrome 4 Absence of serologic evidence of streptococcal infection; 5 Normal levels of C3 in the acute stage of illness 6 Severe Hypertension 7 Unresolving Acute GN:- Massive proteinuria persisting > 4 wks Abnormal renal function (azotemia) - past 2 wks hematuria past 3 wks Urinary sedimentation abnormality persists >18 mo.

32. Post Streptococcal Glomerulonephritis Prognosis Complete recovery in 95% cases Complement returns to normal within 3 wks Microscopic hematuria persists for 1-2 wks Hypertension returns to normal in 2-3 wks 1-5 % Mortality 1 – 5 % develop into Chronic GN, Chronic Renal Failure

33. Membranoproliferative Glomerulonephritis ( Mesangiocapillary Glomerulonephritis) Type-1: Caused by immune complex formation and deposition Of the classical pathway of complement consumption Type 2: Dense Deposit Disease, Mesangiocapillary GN A ssociated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade Type 3: Candidate gene on Chromosome 1 Immune complex deposits were observed under both glomerular endothelial cells and epithelial cells

34. T h a n Q - Dr. C.S.N.Vittal