Aims and objectives Why is renal so difficult? • Demystifying nephrotic and nephritic syndrome • Cover general principles with some examples • Duration: 70 mins • Slides and recordings: www.bitemedicine.com/watch • 2
Case-based discussion: 1 History and examination A 7-year-old presents to the GP with facial swelling which has got progressively worse. Today, his mum noted his ankles were swollen. He has no past medical history. Urine dip Leucocytes -ve, Protein ++++, Blood -ve, Nitrites -ve Observations HR 90, BP 108/72, RR 18, SpO2 95%, Temp 37.0 (1) 3
Case history A 7-year-old presents to the GP with facial swelling which has got progressively worse. Today, his mum noted his ankles were swollen. He has no past medical history. Urine dip Leucocytes -ve, Protein ++++, Blood -ve, Nitrites –ve Observations HR 90, BP 108/72, RR 18, SpO2 95%, Temp 37.0 Q1 Q2 Q3 Q5 Q4 Which of the following is consistent with nephrotic syndrome? Urinary protein 3.0g in 24 hours Macroscopic haematuria Hypocholesterolaemia Hypercoagulability Albumin > 30g/L app.bitemedicine.com 4
Case-based discussion: 1 History and examination A 7-year-old presents to the GP with facial swelling which has got progressively worse. Today, his mum noted his ankles were swollen. Urine dip: Leucocytes -ve, Protein ++++, Blood -ve, Nitrites -ve Observations HR 90, BP 108/72, RR 18, SpO2 95%, Temp 37.0 (1) 5
Introduction Renal failure Pre-renal Renal Post renal
Introduction Renal failure 1. Glomerular Pre-renal Renal Post renal 2. Interstitial 3. Tubular 4. Kidney vascular supply (2)
Introduction Renal failure 1. Glomerular Pre-renal Renal Post renal 2. Interstitial 3. Tubular 4. Kidney vascular supply (2)
Introduction 9
Introduction 10
Introduction Definition: nephrotic and nephritic syndrome are a constellation of symptoms caused by glomerular damage Nephrotic Nephritic Features Proteinuria > haematuria Haematuria > proteinuria • >3.5g per 24hr Hypoalbuminaemia Salt retention Oedema HTN Hypercholesterolaemia Oedema Hypercoagulable state Oliguria Increased risk of infection 11
Pathophysiology Bowman’s capsule 2. 3. 1. Protein and blood (3) 12
Pathophysiology Bowman’s capsule Glomerular capillaries (4) 13
Pathophysiology: Nephrotic syndrome Nephrotic Proteinuria > haematuria Hypoalbuminaemia Oedema Hypercholesterolaemia Hypercoagulable state Increased risk of infection 14
Pathophysiology: Nephritic syndrome Nephritic Haematuria > proteinuria Salt retention HTN Oedema Oliguria 15
Clinical features Nephrotic Nephritic Oedema Oedema Frothy urine Haematuria – often macroscopic Weight gain Weight gain +/- HTN HTN 16
Clinical features (5) (6) 17
Case history A 7-year-old presents to the GP with facial swelling which has got progressively worse. Today, his mum noted his ankles were swollen. He has no past medical history. Urine dip Leucocytes -ve, Protein ++++, Blood -ve, Nitrites –ve Observations HR 90, BP 108/72, RR 18, SpO2 95%, Temp 37.0 Q3 Q5 Q4 Q1 Q2 Which of the following is the most likely diagnosis? Focal segmental glomerulosclerosis Post-streptococcal glomerulonephritis IgA nephropathy Minimal change disease Membranous nephropathy app.bitemedicine.com 18
Aetiology Nephrotic Nephritic Minimal change disease IgA nephropathy Focal segmental glomerulosclerosis Post-streptococcal glomerulonephritis Membranous nephropathy Rapidly progressing glomerulonephritis Amyloidosis Alport syndrome Diabetic nephropathy Membranoproliferative glomerulonephritis Diffuse proliferative glomerulonephritis 19
A 7-year-old presents to the GP with facial swelling which has got Case history progressively worse. Today, his mum noted his ankles were swollen. He has no past medical history. Urine dip Leucocytes -ve, Protein ++++, Blood -ve, Nitrites –ve Observations HR 90, BP 108/72, RR 18, SpO2 95%, Temp 37.0 Q5 Q1 Q3 Q4 Q2 Which of the following would you see on light microscopy in this patient? Normal glomerulus Hypercellularity Fusion of podocytes Thickened basement membrane Segmental glomerulosclerosis app.bitemedicine.com 20
Nephrotic syndrome Nephrotic syndrome Risk factors and comments Most common cause in children Minimal change disease • Usually Idiopathic No change on light microscopy Focal segmental glomerulosclerosis Membranous nephropathy Electron microscopy • Fusion of podocytes Membranoproliferative • Effacement of foot processes glomerulonephritis Responds well to steroids Amyloidosis Diabetic nephropathy 21
Nephrotic syndrome Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative (4) glomerulonephritis Amyloidosis Diabetic nephropathy 22
Nephrotic syndrome Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis Amyloidosis Diabetic nephropathy 23
Nephrotic syndrome Nephrotic syndrome Risk factors and comments Most common cause in adults Minimal change disease • HIV Sickle cell anaemia • Focal segmental • Heroin glomerulosclerosis SLE • Membranous nephropathy Light microscopy Membranoproliferative Segmental sclerosis • glomerulonephritis <50% of glomeruli affected • Amyloidosis Variable response to steroids Diabetic nephropathy 24
Nephrotic syndrome Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy (7) Membranoproliferative glomerulonephritis Amyloidosis Diabetic nephropathy 25
Nephrotic syndrome Nephrotic syndrome Risk factors and comments Most common cause in caucasian adults Minimal change disease • Malignancy Hepatitis B and C • Focal segmental glomerulosclerosis • NSAIDs SLE • Membranous nephropathy Light microscopy Membranoproliferative Thickened basement membrane • glomerulonephritis Amyloidosis Electron microscopy Subepithelial immune complex deposition • Diabetic nephropathy Spike and dome pattern • Variable response to steroids 26
Nephrotic syndrome Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis Amyloidosis Diabetic nephropathy (8) 27
Nephrotic syndrome Nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative glomerulonephritis Amyloidosis Diabetic nephropathy (9) 28
Case-based discussion: 2 History and examination A 20-year-old male presents to the GP complaining of red urine. He is recovering from a sore throat which started 2 days ago. Examination reveals erythematous tonsils. He has no past medical history. Urine dip Leucocytes -ve, Protein +, Blood ++++, Nitrites -ve Observations HR 90, BP 128/85, RR 18, SpO2 95%, Temp 37.0 (10) 29
A 20-year-old male presents to the GP complaining of red urine. He is Case history recovering from a sore throat which started 2 days ago. Examination reveals erythematous tonsils. He has no past medical history. Urine dip Leucocytes -ve, Protein +, Blood ++++, Nitrites -ve Observations HR 90, BP 128/85, RR 18, SpO2 95%, Temp 37.0 Q5 Q4 Q1 Q2 Q3 Which of the following suggests nephritic syndrome? Urinary protein 3.7g in 24 hours Red cell casts Lipid casts White cell casts Brown granular casts app.bitemedicine.com 30
A 20-year-old male presents to the GP complaining of red urine. He is Case history recovering from a sore throat which started 2 days ago. Examination reveals erythematous tonsils. He has no past medical history. Urine dip Leucocytes -ve, Protein +, Blood ++++, Nitrites -ve Observations HR 90, BP 128/85, RR 18, SpO2 95%, Temp 37.0 Q1 Q3 Q5 Q2 Q4 Which of the following is the most likely diagnosis? Rapidly progressive glomerulonephritis Post-streptococcal glomerulonephritis IgA nephropathy Buerger's disease Alport syndrome app.bitemedicine.com 31
Nephritic syndrome Nephritic syndrome Risk factors and comments Most common glomerulonephritis worldwide IgA nephropathy Macroscopic haematuria 1-2 days post viral infection Post-streptococcal glomerulonephritis Immunofluorescence microscopy: IgA complex deposition • Rapidly progressive 30% progress to ESRF glomerulonephritis Steroid not particularly effective Alport syndrome 32
Nephritic syndrome Nephritic syndrome IgA nephropathy Post-streptococcal glomerulonephritis Rapidly progressive glomerulonephritis Alport’s syndrome (11) 33
Nephritic syndrome Nephritic syndrome Risk factors and comments Occurs after Group A strep infection IgA nephropathy Macroscopic haematuria 2 weeks post infection Post-streptococcal Light microscopy: glomerulonephritis Hypercellular glomeruli • Rapidly progressive Electron microscopy glomerulonephritis • Subepithelial immune complex deposits Alport’s syndrome Self-limiting but may progress to RPGN 34
Nephritic syndrome Nephritic syndrome IgA nephropathy Post-streptococcal glomerulonephritis Rapidly progressive glomerulonephritis Alport’s syndrome (12) 35
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