1. Acute Glomerulonephritis

2. Definition and Incidence Acute Glomerulonephritis (acute nephritic syndrome) is the sudden onset of: – Haematuria (macroscopic/microscopic) with red cell casts or dysmorphic RBCs and – Proteinuria in the non-nephrotic range It is often accompanied by: – Hypertension – Oedema (peri orbital, leg or sacral) – Temporary oliguria and uraemia. Acute glomerulonephritis comprises of a specific set of renal diseases where an immune mechanism triggers inflammation causing damage to the basement membrane, mesangium or capillary endothelium of the glomerulus. Glomerulonephritis represents 10-15% of glomerular diseases M:F → 2:1

3. Clinical presentation Symptoms – Dark, scanty urine. – Non-specific symptoms including weakness, fever, abdominal pain and malaise. – Haematuria – Oliguria – Oedema (peripheral or peri orbital) – Headache secondary to hypertension – SOB on exertion and dyspnoea secondary to heart failure or pulmonary oedema – Possible flank pain due to stretching of the renal capsule.

4. Causes – Berger’s disease Also known as IgA nephropathy Commonest form of GN world-wide Pathophys – Focal and segmental proliferative GN with mesangial deposits of IgA – Superimposed crescent formation is frequent Tends to occur in children and young males Clinical pres – Present with asymptomatic microscopic haematuria, proteinuria (5% can be nephrotic). – Can get episodic recurrent haematuria following and URTI or GI viral infection Ix – Normal complement levels – Increased serum IgA (in 50% of cases) – Under immunofluorescence stain: C3, IgM and IgG can be seen in the mesangium Rx – Steroids – All patients should receive a combination of ACEi and ARBs

5. IgA nephropathy

6. Causes - Post-infectious GN Commonly Post-strep GN Occurs 1-3 weeks after a streptococcal infection usually throat, otitis media or cellulitis Pathophysiology – Infecting organism is a group A β-haemolytic streptococcus – The organism is of a nephritogenic type Ix – Biopsy shows diffuse, florid, acute inflammation in the glomerulus (without necrosis but occasionally crescents), with neutrophils and IgG deposition Rx – Acute phase should be treated with antihypertensives, diuretics, salt restriction and possible dialysis – Treat underlying infection if still present

7. Post-strep GN

8. Causes – Henoch-Schonlein syndrome A type of systemic vasculitis deposition of immune complexes in the skin and kidney Clinical presentation – Characteristic skin rash, joint pain, abdo colic and GN Pathophysiology – The lesion is a focal segmental proliferative GN, sometimes with mesangial hypercellularity – Immunoglobulin deposition of IgA is seen in the glomerular mesangium Rx – Oral steroids and steroid-sparing agents

9. Causes – Anti-GBM GN 2/3 of patients with this have Goodpasture’s syndrome with associated lung haemorrhage Pathophys – Characterised by linear capillary loop staining with IgG and C3 – Also has extensive crescent formation – Anti-GBM antibodies are present in serum and are directed against the non-collagenous component of alpha3 collagen in the basement membrane – When anti-GBM antibody binds basement membrane, it activates complement and proteases and results in disruption of the filtration barrier and Bowman’s capsule, causing proteinuria and crescents Rx – Plasma exchange is used to remove circulating antibodies – Steroids – Cyclophosphamide to suppress further antibody synthesis

10. Other causes ANCA-positive vasculitides – Wegener’s granulomatosis – Microscopic polyangiitis – Churg-Strauss syndrome – Characteristic skin rash, joint pain, abdo colic and GN SLE Infective endocarditis Visceral abscess Cryoglobulinaemias Non-strep post-infectious GN Alport’s syndrome

11. Primary  Type I: anti-GBM antibodies  Type II: anti-GBM and immune-deposits (i.e.. SLE, IgA nephropathy, PSGN, MPGN)  Type III: no anti-GBM or immune-deposits (pauci immune); usually ANCA positive o p-ANCA: more often have a clinical picture akin to that of microscopic polyarteritis o C-ANCA: more often have granulomatous disease associated with their glomerulonephritis (ie. Wegener's) Secondary  Membranoproliferative glomerulonephritis  IgA nephropathy—Henoch-Schönlein purpura  Poststreptococcal glomerulonephritis  SLE  Polyarteritis nodosa, hypersensitivity angiitis Rapidly Progressive GN (RPGN) Classification RPGN is defined clinically as nephritic syndrome progressing rapidly to renal failure within weeks to months Histologically defined by the formation of crescents between the Bowman’s capsule and glomerular tuft