1. Glomerular Diseases Dr Rebecca Martin F2

2. 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

4. Exercise 1: Histology of the glomerulus Bowman’s Capsule Capillaries Endothelial cells Mesangium Podocytes (Foot processes) (GBM)

5. Terminology Glomerulonephritis = inflammation of the glomeruli ‘Glomerulopathy’ is a more accurate term NEPHRITIC SYNDROME Collection of symptoms and signs associated with inflammatory glomerular disorders Haematuria Hypertension Oliguria (Oedema) NEPHROTIC SYNDROME Collection of symptoms and signs associated with proliferative glomerular disorders Overt proteinuria (> 3.5g/24h) Hypoalbuminaemia (< 30g/L) Oedema

6. Proteinuria Haematuria SLE IgA nephropathy Minimal change nephropathy Membranous nephropathy Post-infective glomerulonephritis Diabetic nephropathy * Adapted from Davidson’s Principles and Practice of Medicine, 20 th Edition Spectrum of glomerular diseases

7. 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

8. Exercise 2: Glomerular diseases Match the conditions to their histological and clinical features

9. Glomerular diseases CONDITIONHISTOLOGICAL FEATURESCLINICAL FEATURES Minimal change nephropathy Usually normal histologyGood response to steroids Membranous nephropathyThickened GBMCommonest cause of nephrotic syndrome in adults IgA nephropathyIncreased mesangial matrixCommon cause of ESRF Post-infective glomerulonephritis Diffuse proliferation of endothelial/mesangial cells, infiltration by neutrophils Usually resolves spontaneously

10. 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

11. 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

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

13. 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 glomerulonephritis General term Extreme inflammatory nephritis Loss of renal function over days to weeks Biopsy can show necrotising lesions in glomerulus Goodpasture’s disease > SLE > IgA nephropathy.

14. 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

15. Exercise 3: Case based discussion 24 year old male presents to medical outpatient clinic More tired than usual No systemic symptoms on questioning Only 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?

16. Investigations in glomerular disease Bedside tests Urine dip Laboratory tests FBC, U&E, CRP, ESR, HbA1C, complement, ANCA, ANA, anti- dsDNA, anti-GBM, ASOT Urine microscopy, urine albumin:creatinine ratio, 24h protein Throat/skin swabs Imaging Renal ultrasound Invasive tests Renal biopsy

17. 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?

18. Summary Nephritic and nephrotic syndromes Archetypal diseases for each Key investigations to perform Management principles

19. 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

20. Thank you Any questions?