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 Q4 Q5
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 Pre-renal 1. Glomerular 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.
Protein and blood 1.
(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
Q1 Q2 Q3 Q4 Q5
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 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 Q4 Q5
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 Focal segmental glomerulosclerosis No change on light microscopy
Membranous nephropathy Electron microscopy • Fusion of podocytes Membranoproliferative • Effacement of foot processes glomerulonephritis Amyloidosis Responds well to steroids
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 • Focal segmental Sickle cell anaemia glomerulosclerosis • Heroin • 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 • Focal segmental glomerulosclerosis Hepatitis B and C • NSAIDs Membranous nephropathy • SLE 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 Case history 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
Q1 Q2 Q3 Q4 Q5
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 Case history 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
Q1 Q2 Q3 Q4 Q5
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 glomerulonephritis 30% progress to ESRF 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 Nephritic syndrome
Nephritic syndrome Risk factors and comments Multiple causes: IgA nephropathy • Post-streptococcal glomerulonephritis • Post-streptococcal glomerulonephritis Goodpasture syndrome • Granulomatosis with polyangiitis Rapidly progressive • Churg-Strauss syndrome glomerulonephritis • Microscopic polyangiitis Alport’s syndrome Light microscopy • Inflammatory crescents in Bowman’s space Immunofluorescence microscopy: • Can help determine aetiology Progresses to renal failure in weeks to months
36 Nephritic syndrome
Nephritic syndrome
IgA nephropathy
Post-streptococcalRapidly progressive glomerulonephritis glomerulonephritis RapidlyAlport’s progressive syndrome glomerulonephritis Alport’s syndrome
(13) 37 Investigations: General principles Bedside • Urinalysis: • Proteinuria vs haematuria • Casts: lipid (nephrotic) vs red cell (nephritic) • 24-hour urinary protein collection: >3.5g/24hr is suggestive of nephrotic syndrome • Urine albumin:creatinine ratio raised due to proteinuria
Bloods • U&Es: monitor eGFR and creatinine to assess for renal failure • LFTs: hypoalbuminemia < 25-30 g/L in nephrotic syndrome • Lipid profile: hypercholesterolaemia and hypertriglyceridemia • Complement: may be depleted depending on cause e.g. PSGN
Special tests • Renal biopsy: light and electron microscopy to assess glomerular damage
38 Management: General principles
Lifestyle • Improve cardiovascular risk factors
Immunosuppression • Steroids • DMARDs • Ciclosporin • Cyclophosphamide
Adjunctive treatment • ACEi: reduces proteinuria
39 Complications & Prognosis
Complication Prognosis: • MCD: good prognosis and responds to steroids • FSGS: variable • Renal failure • IgA: 25-30% progress to end-stage renal failure
• CV risk • Infection • Thrombosis
40 Top-decile question
41 Recap
• Glomerular disease leads to nephrotic and nephritic syndrome
• Nephrotic: protein > blood
• Nephritic: blood > protein
(1) • Many causes of which the commonest are MCD, FSGS, and IgA nephropathy
• Investigate with urinalysis, bloods, and biopsy
• Management may require immunosuppression
(10)
42
References
1. Polarlys / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 2. Modified. CKRobinson / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 3. Pharmattila / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 4. Modified. Ed Uthman (Pathologist), website: [2] / CC BY-SA (https://creativecommons.org/licenses/by-sa/2.0) 5. Nephrotic syndrome / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 6. James Heilman, MD / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 7. Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 8. Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 9. Renal_corpuscle.svg: M•Komorniczak -talk- (polish Wikipedist)derivative work: Huckfinne / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 10. James Heilman, MD, Attribution-Share Alike 4.0 International license. 11. Lazarus Karamadoukis, Linmarie Ludeman and Anthony J Williams / CC BY (https://creativecommons.org/licenses/by/2.0) 12. Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 13. Modified. Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)
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