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?
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