Nephritic Sx & Nephrotic Sx

1. Nephritic Sx & Nephrotic Sx

2. Case report 1 • 18 yr old man • Bilateral loin pain • Macroscopic haematuria • Sore throat started one day earlier • BP 140/90; euvolaemic • Creatinine 120 μmol/l • Proteinuria and haematuria on dipstix

3. Case Report 2 • 20 yr old lady • Completely well • Haematuria on dipstix • No proteinuria • Normotensive

4. Case Report 3 • 12 year old boy • Impetigo two weeks earlier • Headache • Oliguric • Frothy dark coloured urine • Hypertensive

5. 15yr old woman 3/12 ankle swelling; face and fingers swollen in the am BP 130/80; JVP normal; Leg oedema Creatinine 54 μmol/l Cr Cl 140 ml/min Albumin 18 g/l 24 hr u.protein 10 g Case report 4

6. Case Report 5 • 30 year old man,diabetic • Known hypertensive • Ankle oedema • Dipstix: ++++ proteinuria • Creatinine 124 μmol/l (80 – 120) • Albumin 30 g/l (36 – 45)

7. Case Report 6 • 50 year old obese man • Hypertension 10 years • NIDDM 3 years • No retinopathy • Creatinine 124 μmol/l • 24 hr urine protein 2 g • HbA1 9.6%

10. Structure of the filtration barrier Podocyte Foot processes Fenestrated endothelium

11. Minimal change disease

12. Glomerular changes in disease • Proliferation • Sclerosis • Necrosis • Increase in mesangial matrix • Changes to basement membrane • Immune deposits • Diffuse vs focal • Global vs segmental

13. Common Syndromes • Nephrotic Syndrome • Nephritic Syndrome • Rapidly Progressive GN • Loin Pain Haematuria Syndrome

14. Features of Glomerular Disease • Proteinuria • Haematuria • Renal Failure • Salt and Water Retention • Loin Pain

15. Salt and Water Retention • Hypertension • Oedema • Oliguria

16. Loin Pain • Rare

17. Proteinuria • Marker of renal disease • Risk factor for cardiovascular disease • Dyslipidaemia • Hypertension • Something more? • 24 hr protein vs urine protein:creatinine ratio

18. Nephrotic syndrome • Proteinuria > 40 mg/m2*hr • Hypoalbuminaemia (<2.5mg/dl) • Oedema • Hyperlipidemia • Thromboses • Infection

19. Learning Points • Clinical features • Commonest types • Prognosis • Causes • Treatments

20. Nephrotic Syndrome • Causes of primary idiopathic NS • Minimal change disease • Mesangial proliferation • Focal segmental glomerulosclerosis

21. Minimal Change Disease • Usually children • Nephrotic syndrome with highly selective proteinuria and generalised oedema • Rarely hypertension or ARF • T cell mediated – VPF • Steroid sensitive usually • Spectrum of disease to FSGS

22. Focal Segmental Glomerulosclerosis • Juxtamedullary glomeruli – may be missed due to sampling error • Older patients • Less sensitive to immunosuppression • Hypertension, haematuria, progressive CRF

23. FSGS: • Familial • VUR • Drug abuse • Obesity

24. Common types of GN Primary • Thin membrane disease • IgA disease • Minimal Change / FSGS spectrum • Membanous Nephropathy Secondary • PSGN & Diabetic Glomerulosclerosis

25. Rarer Types • Diffuse endocapillary proliferative GN (post infectious GN) • Crescentic GN • Membanoproliferative / mesangiocapillary GN

26. Nephritic Syndrome • Haematuria • Hypertension • Oliguria • Edema

27. Rapidly progressive GN • Nephritic or nephrotic onset • ESRF in six months

28. General Treatment of GN • Control BP • Angiotensin blockade • Statin • Lose weight • Stop smoking • (pneumococcal prophylaxis) • (anticoagulation)

29. Help! I need a volunteer!

31. Case report 1 • 18 yr old man • Bilateral loin pain • Macroscopic haematuria • Sore throat started one day earlier • BP 140/90; euvolaemic • Creatinine 120 μmol/l • Proteinuria and haematuria on dipstix

32. Case 1: indicative answers • IgA Disease • Renal failure, proteinuria, haematuria, oedema, hypertension, oliguria, loin pain • All except oedema and oliguria

33. Mesangial IgA disease • Classical Berger’s Disease • Microscopic haematuria • Proteinuria (rarely nephrotic) • Hypertension • Chronic renal failure • ? Failure of hepatic clearance of IgA • Association with GI disease • No specific treatment

34. Ig A Nephropathy • Ig A nephropathy is the most common primary GN worldwide • Usually present with hematuria • Episodes of gross hematuria are precipitated by flu like illness, exercise • Urinary protein excretion usually non-nephrotic • Associated with chronic liver ds, psoriasis, IBD and HIV disease.

35. Ig A Nephropathy • Only 30% of patients with IgA nephropathy has progressive disease. • In progressive disease, use of fish oil may be beneficial. • Immunosuppressive therapy in patients with Ig A nephropathy has not consistently shown to be of benefit

36. Case Report 2 • 20 yr old lady • Completely well • Haematuria on dipstix • No proteinuria • Normotensive

37. Case 2: indicative answers • Exclude menstruation! • Thin membrane disease (possibly IgA disease) • Commonest cause of isolated microscopic haematuria in this age group. • At this age, urological cause unlikely; nil to suggest infection / urolithiasis

38. Thin membrane disease • Most common GN • Microscopic haematuria • Familial • Benign • No treatment needed • Most young people with isolated microscopic haematuria have thin membrane disease

39. Case Report 3 • 12 year old boy • Impetigo two weeks earlier • Headache • Oliguric • Frothy dark coloured urine • Hypertensive

40. Case 3: indicative answers • Acute nephritic syndrome • Post-streptococcal glomerulonephritis • Diffuse proliferative endocapillary glomerulonephritis • Due to salt and water retention, so salt restriction or loop diuretic

41. Acute Post-Infectious GN • Usually occur in children • Post-streptococcal GN is the most common cause of post infectious GN • Occurs after a streptococcal sore throat or impetigo • Caused by Group A, beta-hemolytic streptococci, particularly nephritogenic strains – Type 1,4,12 (throat) and 2,49(skin)

42. Acute Post-Infectious GN • Acute onset of gross hematuria (COLA COLORED) or microscopic hematuria after latent period of 10-14 days. • Edema/hypertension • RBC casts on U/A • Elevated creatinine, increased ASO titer • Decreased complement level

43. Acute Post-Infectious GN • LM – Diffuse proliferative and exudative GN • IF – IgG and C3 “lumpy, bumpy” • EM – Sub epithelial “Hump” or “Flame” like deposits

44. Diffuse Endocapillary Proliferative GN (Post Streptococcal GN) Diffuse endocapillary proliferative GN Post infectious; usually Gp A Strep Acute nephritic syndrome Uraemia rare Self-limited; rarely death from BP Abnormal RUA for up to 2 yrs Circulating immune complex mediated

45. Acute Post-Infectious GN • Renal biopsy is generally not required. • Treatment is supportive and consist of sodium restriction, control of BP and dialysis if this become necessary.

46. Complications of the Nephritic Syndrome • Hypertensive encephalopathy (seizures, coma) • Heart Failure (pulmonary oedema) • Uraemia requiring dialysis

47. Prognosis in the Nephritic Syndrome • More than 95% of children make a complete recovery • Chronic renal impairment in the longer term is uncommon in children • Bad prognostic features include severe renal impairment at presentation and continuing heavy proteinuria and hypertension • Adults more likely to have long term sequellae than children

48. 15 yr old girl 3/12 ankle swelling; face and fingers swollen in the am BP 130/80; JVP normal; Leg oedema Creatinine 54 μmol/l Cr Cl 140 ml/min Albumin 18 g/l 24 hr u.protein 10 g Case report 4

49. Case 4: indicative answers • Minimal change – focal segmental glomerulosclerosis spectrum • Very nephrotic • Age and borderline BP make FSGS more likely than MCN • Effect of loss of colloid osmotic pressure gradient across glomerulus causing hyperfiltration

50. Case Report 5 • 30year old man,diabetic • Known hypertensive • Ankle oedema • Dipstix: ++++ proteinuria • Creatinine 124 μmol/l (80 – 120) • Albumin 30 g/l (36 – 45)