Glomerulonephritis - Kidney Disease

Glomerulonephritis

Overview

·        Variety of conditions ® inflammatory changes in the glomeruli. If severe enough to cause crescent formation Þ rapidly progressive glomerulonephritis 

·        Some forms predominantly present in one way, but any form can present in any way.  Can present as:

o   Nephritic Syndrome

o   Nephrotic Syndrome

o   Acute Renal Failure secondary to rapidly progressive GN

o   Chronic Renal Failure

o   Asymptomatic Haematuria or proteinuria

o   Hypertension

·        Either:

o   Primary: limited to the kidney

o   Secondary: part of a more widely disseminated immune process

·        Systemic diseases that may present as GN:

o   Lupus nephritis: deposits of immune complexes everywhere within the glomerulus

o   Arteritis: Microscopic polyarteritis

o   Amyloid: Nephrotic Syndrome or renal failure.  Histology with Congo Red Stain

o   Diabetes

o   Hypertension

·        Terminology:

o   Proliferative: proliferation of endogenous glomeruli cells

o   Exudative: infiltration by polymorphs

o   Diffuse:  involves all glomeruli

o   Focal: involves only some glomeruli

o   Global: involves the whole glomerular tuft

o   Segmental: involves only part of the glomerular tuft

·        Diagnosis: 

o   Urine biochemistry: urine sodium > 20 mmol/L (if pre-renal failure then < 20, ie frantically trying to reabsorb Na)

o   Urine analysis: Blood morphology and casts, protein (usually mild) 

o   Ultrasound: exclude obstruction, looking for normal or slightly enlarged kidneys, echogenic (dark on US Þ ­fluid)

o   CXR: look for Goodpastures Syndrome, Wegener‟s Granulomatosis

o   Bloods: ANA (connective tissue disorders), ANCA (Anti-neutrophil cytoplasmic antigen Þ 

o   Wegener‟s Granulomatosis), Anti-dsDNA (Þ SLE), anti-GBM

·        Histology.  May see: 

o   Glomerula epithelial cells usually have interdigitating foot processes. If they swell, ¯ gaps between them ® proteinuria 

o   Mesangial cells (supporting framework) are the first to react to injury and the last to return to normal

Management

·        Investigations:

o  Urine microscopy

o  24 hour urine for protein and Cr

o  Serum: U&E, FBC, ESR, CRP, albumin, ANAs, etc

o  Culture: ?blood, throat, ears, skin

o  CXR, US, IVU

o  Biopsy

·        Treatment:

o  Prompt referral

o  Keep BP < 145/90

o  Specific treatment

o  Monitor renal function

Clinical and lab features

Minimal Change Disease

·        Presentation: 

o  Usually nephrotic syndrome, with severe oedema, uncommonly have hypertension and 10% have microscopic haematuria

o  Commonly after an URTI

o  Boys > girls

o  90% of childhood nephrotic syndrome, 20 – 30% of adult nephrotic syndrome

o  Renal function normal, unless it deteriorates secondary to hypovolaemia

o  Weak association with Hodgkin‟s Disease

·        Investigations:

o  Light Microscopy (LM): glomeruli are normal

o  Immunoflourescence (IF): Negative

o  Electron Microscopy (EM): fusion of foot processes

·        Management:

o  Kids: natural history unpredictable: 

§  90% of kids respond to 8 weeks of steroids. If they relapse, respond to steroids again (eg triggered by intercurrent illness). No renal failure but complications of treatment 

§  10% become steroid dependent or resistant ® use cyclosporin

o  Steroids less effective in adults, but still reasonable response rate

Focal and Segmental Glomerulosclerosis (FSGS)

·        Presentation:

o   Usually nephrotic, can be nephritic

o   Usually microscopic haematuria

o   Accounts for 10 – 20% of nephrotic syndrome in adults

·        Investigations: 

o   LM: segmental sclerosis of the glomerular tufts. May be ­mesangial matrix, interstitial fibrosis and tubular atrophy 

o   IF: Weakly positive for IgM and C3 (?artefact)

·        Management:

o   Poor prognosis: 50% have a five year renal survival

o   Some response but frequent relapse to steroids

Membranous Glomerulonephritis

·        Presentation:

o   Nephrotic syndrome, also asymptomatic proteinuria

o   Microscopic haematuria, hypertension, renal impairment

o   30% of adult nephrotic syndrome, most commonly middle-aged

·        Usually idiopathic, but 25% of it is secondary to underlying disease, including:

o   Lung or colon cancer (< 10% or adults presenting with Membranous GN)

o   Infections: hepatitis B, malaria

o   SLE

o   Drugs: penicillamine, gold, high dose captopril

·        Investigations:

o   Is autoimmune – but there is no antibody you can measure

o   LM: thickened, irregular capillary loops, spikes in BM with silver stain

o   IF: granular deposition of IgG and C3

o   EM: Subepithelial deposits 

·        Prognosis: variable – 30% progress to end-stage, 30% improve, and the rest retain stable renal function but with ongoing proteinuria 

·        Treatment: steroids or cytotoxics for the progressive group

Post-Infectious Glomerulonephritis

·        8 – 14 days following Group A b-haemolytic strep infection of throat or skin, also SBE, osteomyelitis, etc 

·        Cultures usually negative, strep serology may be helpful 

·        Presentation: Usually nephritic, may be rapidly progressing ® acute renal failure

·        Biopsy: usually in adults to rule out a crescentic rapidly progressive GN:

o   LM: mesangial and endothelial cell proliferation + neutrophils.  Crescents if severe

o   IF: Usually +ive for granular IgG and C3 deposition

·        Treatment: supportive, not immunosuppressive.  Treat culture positive family members with penicillin

·        Prognosis: slow recovery, mild residual impairment in a few

Goodpasture’s Syndrome

·        GN +/- pulmonary involvement (ranging from pulmonary infiltrate on x-ray to frank haemoptysis) 

·        Pathogenesis: antibodies against an antigen in the glomerular basement membrane and pulmonary tissue 

·        Biopsy: Crescents + linear immunoflourescence on the basement membrane

·        Can measure serum anti-GBM antibody

·        Treatment: immunosuppression (steroids, cyclophosphamide) +/- plasmapheresis

Mesangial IgA disease (Berger’s Disease)

·        Most common form of GN. Common cause of recurrent haematuria in young men. Usually more benign

·        Presentation, either:

o   Macroscopic haematuria +/- URTI (= Synpharyngetic haematuria)

o   Asymptomatic microscopic haematuria picked up on dipstick testing

o   Nephrotic levels of proteinuria are rare

·        Biopsy:

o  LM: Mesangial cell proliferation + ­ matrix formation

o  IF: Mesangial deposits of IgA and C3

·        Prognosis: only 15 – 20% progress to end-stage renal failure – these are more likely to have proteinuria, hypertension and impaired renal function at presentation

·        No effective treatment.  Consider immunosuppressive treatment if rapidly progressive 

·        Similar to Henoch-Scholein Purpura – but HSP is more widespread, causing purpura (especially buttocks and ankles) and abdominal pain (which may ® GI bleeding)

Mesangiocapillary (Membranoproliferative) GN*

·        50% present as Nephrotic Syndrome

·        Biopsy:

o  LM: cellular expansion of the mesangium.  „Twin track‟ BM

o  EM: Subendothelial deposits or deposits within the BM

Rapidly Progressive Glomerulonephritis

·        What is it:

o  A description not a diagnosis

o  = Acute renal failure secondary to glomerula disease generally with a nephritic presentation. 

o  Any form of GN can present in a rapidly progressive form. Generally caused by immune mediated diseases

·        ~ Crescentic glomerulonephritis (marker for severe RPGN)

o  = Cellular proliferation in glomeruli, and crescent formation. 

o  Pathogenesis of crescents: rupture of the basement membrane ® fibrin leaks into Bowman‟s space, macrophages recruited, epithelioid cells form a crescent. Leads to scarring and fibrosis of glomeruli 

·        Presentation:

o  Nephritic presentation.  Nephrotic range proteinuria is rare

o  ® ¯GFR but tubular function OK so Na/H₂0 reabsorbed ® oedema

o  Systemic features of immune mediated diseases: myalgia, arthralgia, fever, etc

·        Investigations:

o  Urine chemistry midway between pre-renal ARF and ATN 

o  Light Microscope: Extensive proliferation of cells, numerous crescents, generally without polymorphs

o  Immunoflouresence:

§  Granular IgG and C3 Þ immune complex mediated (Post strep, Lupus, etc) 

§  Linear IgG Þ Goodpastures

§  None Þ pauci-immune

·        Due to:

o  Immune complex mediated GN: 

§  Post-infectious GN: e.g. post-streptococcal (rarely crescents, dialysis rarely needed) also staph. Has granular IgG plus neutrophils

§  Lupus Nephritis, Has granular IgG (plus IgA, IgE, etc)

§  Others, including vasculitis

o  Anti-glomerular-basement membrane diseases (Goodpasture‟s syndrome) 

o  Pauci-immune: (ie no evidence of immune deposits, probably cell mediated immune problem): 

§  Wegener‟s Granulomatosis: Causes GN, URTI, LRTI, non-caseating granuloma, cANCA is highly specific, -ive immunoflourescence, typically older patients. 

§  Microscopic polyarteritis (also joints)

·        Prognosis dependent on % of crescents

·        Treatment: immunosuppressive (iv methylprednisolone, cyclophosphamide) +/- dialysis