Glomerular Diseases

Dr Rebecca Martin F2

Learning objectives

1. Appreciate the fact that glomerular diseases fall onto a wide spectrum

2. Be able to define the nephritic and nephrotic syndromes

3. Understand the pathology of 4 key glomerular diseases which serve as archetypal examples of nephritic and nephrotic syndrome

4. Know how to assess and manage a patient with suspected glomerular disease

Exercise 1: Histology of the glomerulus

Bowman’s Capsule

Capillaries

Endothelial cells

Mesangium

Podocytes

(Foot processes)

(GBM)

TerminologyGlomerulonephritis = inflammation of the glomeruli‘Glomerulopathy’ is a more accurate term

NEPHRITIC SYNDROMECollection of symptoms and signs associated with inflammatory glomerular disorders

• Haematuria• Hypertension• Oliguria • (Oedema)

NEPHROTIC SYNDROMECollection of symptoms and signs associated with proliferative glomerular disorders

• Overt proteinuria (> 3.5g/24h)• Hypoalbuminaemia (< 30g/L)• Oedema

Proteinuria

Haematuria

SLE

IgA nephropathy

Minimal change

nephropathy

Membranous nephropathy

Post-infective glomerulonephritis

Diabetic nephropathy

* Adapted from Davidson’s Principles and Practice of Medicine, 20th Edition

Spectrum of glomerular diseases

Presenting features of glomerular disease

SYMPTOMS• Asymptomatic• Fatigue, lethargy• Haematuria• Frothy urine• Swelling• Oliguria

SIGNS• Hypertension• Oedema • Positive urine dipstick for

protein/blood• Signs of related pathology

Exercise 2: Glomerular diseasesMatch the conditions to their histological and clinical features

Glomerular diseasesCONDITION HISTOLOGICAL FEATURES CLINICAL FEATURES

Minimal change nephropathy

Usually normal histology Good response to steroids

Membranous nephropathy Thickened GBM Commonest cause of nephrotic syndrome in adults

IgA nephropathy Increased mesangial matrix Common cause of ESRF

Post-infective glomerulonephritis

Diffuse proliferation of endothelial/mesangial cells, infiltration by neutrophils

Usually resolves spontaneously

Glomerular diseases 1

Minimal change nephropathy- Commonest cause of nephrotic syndrome in children- Accounts for 25% adult nephrotic syndrome- Proteinuria usually remits on high dose steroids- Does not progress to CKD- Issues: nephrotic syndrome and complications of treatment

Membranous nephropathy- Commonest cause of nephrotic syndrome in adults- 1/3 spontaneous resolution, 1/3 remain in nephrotic state,

1/3 progress to CKD- Watch and wait/steroids/cyclophosphamide

Glomerular diseases 2

IgA nephropathy- Common cause of ESRF- Commonest cause of nephritic syndrome- Acute exacerbations can occur, particularly with respiratory

infections - Mild variant associated with HSP in children - Poor response to immunosuppressive therapy

Henoch-Schonlein Purpura• Systemic vasculitis• 3-10 years M:F 2:1• Skin rash, arthralgia, abdominal pain• 40% glomerulonephritis (IgA

nephropathy)

Glomerular diseases 3

Post-infective glomerulonephritis- More common in children, now rare in developed world- 10 day latency, usually after streptococcal throat infection- Renal function improves spontaneously after 10-14 days- Management by fluid and sodium restriction

Rapidly progressive glomerulonephritisGeneral termExtreme inflammatory nephritisLoss of renal function over days to weeksBiopsy can show necrotising lesions in glomerulusGoodpasture’s disease > SLE > IgA nephropathy.

Diabetic nephropathy • Commonest cause of ESRF in UK• 30% with T1DM develop after 20 years • Poor glycaemic control strongest risk factor• Microalbuminuria is earliest indicator • Treatment with good glycaemic control and ACEi

Thickening of GBM

Increased mesangial matrix

Nodular deposits

Glomerulosclerosis and loss of glomeruli

Microalbuminuria (Albumin: creatinine ratio > 2.5 M > 3.5 F)

Heavy proteinuria

Exercise 3: Case based discussion

24 year old male presents to medical outpatient clinicMore tired than usualNo systemic symptoms on questioningOnly thing he has noticed is his urine is frothy

Group 1: What else would you like to ask in the history?Group 2: What would you examine?Group 3: What investigations would you perform?

Investigations in glomerular disease

Bedside testsUrine dip Laboratory testsFBC, U&E, CRP, ESR, HbA1C, complement, ANCA, ANA, anti-

dsDNA, anti-GBM, ASOT Urine microscopy, urine albumin:creatinine ratio, 24h proteinThroat/skin swabsImagingRenal ultrasound Invasive testsRenal biopsy

Management of glomerular diseases

• Refer to a nephrologist!• Control hypertension (BP <130/80)• Tight control of blood glucose if appropriate• Restrict fluid and salt intake if proteinuria• Watch and wait?• Steroids?• Immunosuppressants?

Summary

• Nephritic and nephrotic syndromes• Archetypal diseases for each• Key investigations to perform • Management principles

Learning at home

• Please link this evening’s learning to rheumatology teaching

• SLE and Goodpasture’s disease (anti-GBM) are also causes of glomerulopathy

• These are potential causes of rapidly progressive glomerulonephritis

Thank you

Any questions?