Nephrotic and Nephritic Syndrome

1. Dr Claire Gibbons FY2 Claire.gibbons@doctors.org.uk Nephrotic and Nephritic Syndrome

2. Learning Objectives • Understand and define nephrotic and nephritic syndromes. • Describe the initial investigations and management of nephrotic and nephritic syndromes. • Describe the complications of nephrotic and nephritic syndromes.

3. Draw a nephron!

5. Glomerulonephritis • Glomerulus – capillary loop with basement membrane which allows passage of specific molecules into the nephron • Glomerulonephritis – inflammation/damage of the glomerular basement membrane resulting in altered function. Relatively uncommon cause of kidney injury. • Can present as nephrotic and/or nephritic syndrome.

6. What is nephrotic syndrome? • Increased permeability of the glomerulus leading to loss of proteins into the tubules.

7. Nephrotic Syndrome • Triad of: • MASSIVE Proteinuria >3g/24hours • Or spot urine protein:creatinine ratio >300-350mg/mmol • Hypoalbuminaema <25g/L • Oedema • And often: • Hypercholesterolaemia/dyslipidaemia (total cholesterol >10mmol/L)

8. Presentation • New-onset oedema • Initially periorbital or peripheral • Later genitals, ascites, anasarca • Frothy urine • Generalised symptoms – lethargy, fatigue, reduced appetite

9. Further possible presentations... • Oedema • BP normal/raised • Leukonychia • Breathlessness: • Pleural effusion, fluid overload, AKI • DVT/PE/MI • Eruptive xanthomata/ xanthalosmata

10. You are a GP with the following patients... • Young, fit 24 year old male complaining of frothy urine. • 10 year old boy with puffy eyes. • 74 year old female with multiple co-morbidities and swollen ankles.

11. Differential Diagnosis for Oedema • Congestive Cardiac Failure • Raised JVP, pulmonary oedema, mild proteinuria • Liver disease • Hypoalbuminaemia, ascites/oedema • What investigations can you do? • You decide to send your patient to the renal clinic...

12. Causes of Nephrotic Syndrome • Primary glomerulonephritis • Minimal change disease (80% paeds cases) • Focal segmental glomerulosclerosis (most common cause in adults) • Membranous glomerulonephritis

13. Systemic Causes • Secondary glomerulonephritis • Diabetic nephropathy • Sarcoidosis • Autoimmune: SLE, Sjogrens • Infection: Syphilis, hepatitis B, HIV • Amyloidosis • Multiple myeloma • Vasculitis • Cancer • Drugs: gold, penicillamine, captopril, NSAIDs

14. Investigations • Urine dipstick and send to lab • Urine microscopy • Bloods – the usual ones, plus renal screen • Immunoglobulins, electrophoresis (myeloma screen), complement (C3, C4) autoantibodies (ANA, ANCA, anti-dsDNA, anti-GBM) • Renal ultrasound • Renal biopsy (all adults) • Children generally trial of steroids first

15. Management • Conservative • Monitor U&E, BP, fluid balance, weight • Salt and fluid restriction • Treat underlying cause • Medical • Diuretics • ACE-inhibitors/ARBs • Corticosteroids/immunosuppression • Dialysis • Anticoagulation • Surgical • Renal transplant

16. Complications • Increased susceptibility to infection • 20% adult cases • Due to reduced serum IgG, reduced complement activity, reduced T cell function • Thromboembolism • 40% adult cases • Partly due to increased clotting factors and platelet abnormalities • Hyperlipidaemia • due to hepatic lipoprotein synthesis to restore osmotic pressure

17. Prognosis • Varies • With treatment, generally good prognosis • Especially minimal change disease (1% progress to ESRF) • Without treatment, very poor prognosis • Children under 5 or adults older than 30 = worse prognosis

18. What is nephritic syndrome?

19. Pathophysiology • Thin glomerular basement membrane with pores that allow protein and blood into the tubule.

20. Nephritic Syndrome • Clinical syndrome defined by: • Haematuria/ red cell casts • Hypertension (mild) • Oliguria • Uraemia • Proteinuria (<3g/24 hours)

21. Signs and Symptoms • Haematuria (E.g. cola coloured) • Proteinuria • Hypertension • Oliguria • Flank pain • General systemic symptoms • Post-infectious = 2-3 weeks after strep-throat/URTI

22. What are your differentials? • Malignancy (older patients) • UTI • Trauma • What bedside investigation would you like to do? • You decide to refer to the renal clinic...

23. Causes • Post-infectious glomerulonephritis • Primary • IgA Nephropathy (Berger's disease) • Rapidly progressive glomerulonephritis • Proliferative glomerulonephritis • Secondary glomerulonephritis • Henoch-Schonlein purpura • Vasculitis

24. Investigations • Urine dipstick and send sample to lab • Urine microscopy – red cell casts • Bloods – the usual plus renal screen • Immunoglobulins, electrophoresis, complement (C3, C4) autoantibodies (ANA, ANCA, anti-dsDNA, anti-GBM); blood culture; ASOT (anti-streptolysin O titre) • Renal ultrasound • Renal biopsy

25. Red Cell Casts

26. Management • Conservative • Monitor U&E, BP, fluid balance, weight • Salt and fluid restriction • Treat underlying cause • Medical • Diuretics • Treat hypertension • Corticosteroids/immunosuppression • Dialysis • Surgical • Renal transplant

27. Prognosis • Varies • Post-infectious usually self-resolving (95% recover renal function) • Others are a bit more nasty

28. Example Case

29. Summary • Nephrotic syndrome = MASSIVE proteinuria • Nephritic syndrome = haematuria/red cell casts • May be a mixed presentation • New oedema? Dipstick that urine! • Haematuria? Exclude malignancy!

30. Any Questions? Claire.gibbons@doctors.org.uk

31. Sources • Oxford Handbook of Clinical Medicine • Oxford Handbook for the Foundation Programme • Essential Revision Notes for the MRCP • Www.almostadoctor.com • Www.pathologystudent.com