Glomerular Disease (Clinical) Flashcards
1
Q
4 features of glomerulonephritis? (HRHP)
A
- Haeamaturia
- Renal insufficiency
- Hypertension
- Proteinuria
2
Q
Describe appearance of both microscopic and macroscopic haematuria
A
Macroscopic - tea/cola coloured or frank blood
Microscopic - blood not visible to naked eye; =>5 RBC per high power field
3
Q
What is the basic difference between nephrotic and nephritic syndrome?
A
NEPHROTIC = loss of a lot of protein
NEPHRITIC = loss of a lot of blood
4
Q
Which syndrome is more likely to involve haematuria?
A
Nephritic
5
Q
Where can blood in haematuria come from?
A
Kidney
Ureter
Bladder
Prostate
Urethra
(anywhere in renal tract!)
6
Q
In glomerulonephritis, persistent microscopic haematuria shows what on microscopy?
A
Dysmorphic ‘Mickey-mouse like’ RBCs
7
Q
What are the 3 ways to classify proteinuria?
A
- Glomerular or tubular (glomerular - from increased permeability of glomerular membrane; tubular - from reduced tubular function)
- Albuminuria or proteinuria (both describe abnormal protein excretion in urine - one more focused on albumin)
- Persistent or transient
8
Q
Is protienuria more a nephrotic or nephritic syndrome?
A
They are equal (use urine dipstick to see what side its likely to be on)
9
Q
What are the 2 ways to diagnose proteinuria?
A
Urine protein creatinine ratio
24 hr urine collection
10
Q
In glomerulonephritis, what is the nature of proteinuria?
A
Persistent proteinuria of more than 1 gram/mmol of creatinine
11
Q
What is the definition of hypertension?
A
>140/80mmHg
12
Q
Is hypertension more a nephritic or nephrotic syndrome symptom?
A
Nephritic
13
Q
Hypertension is usually found in renal insufficiency, how is RI diagnosed and what are the ways to classify it?
A
Rising creatinine !
- Nephritic > nephrotic
- Mild or severe
- Slow or rapid deterioration
14
Q
3 fetaures of nephritic state
A
- Active urine sediment: haematuria, dysmorphic RBCs, cellular casts
- Hypertension
- Renal impairment
15
Q
4 features of nephrotic syndrome
A
- Oedema
- Proteinuria > 3.5g/day
- Hypoalbuminaemia
- Hyperlipidaemia
16
Q
What 2 things can nephrotic syndrome be caused by?
A
Primary (idiopathic) glomerular disease - only glomerulus
Secondary glomerular disease - other parts of body e.g. lupus, SLE
(diabetes is most common cause)
17
Q
2 differential diagnoses for nephrotic syndrome? How to differentiate them?
A
- Congestive Heart Failure (JVP raised, normal albumin, minimal proteinuria)
- Hepatic disease (abnotmal LFTs, no proteinuria)
18
Q
3 ways to classify glomerulonephritis?
A
- Aetiology*: autoimmune, infection, malignancy, drugs, others
- Primary v secondary* i.e. kideny alone or part of multisystem disease
- Morphological*
19
Q
Define proliferative vs non-proliferative glomerulonephritis
A
Proliferative = excessive numbers of cells in glomeruli; these include infiltrating leukocytes
Non-proliferative = glomeruli look normal or have areas of scarring; they have normal numbers of cells
20
Q
How is diffuse glomerulonephritis defined?
A
>50% of glomeruli affected
21
Q
How is focal glomerulonephritis defined?
A
<50% of glomeruli affected
22
Q
How is global glomerulonephritis defined?
A
All of glomerulus affected
23
Q
How is segmental glomerulonephritis defined?
A
Part of glomerulus affected
24
Q
What glomerulonephritis syndrome causes urinary sediment abnormalities and proteinuria?
A
IgA nephropathy
25
What types of glomerulonephritis are associated with nephrotic syndrome?
Minimal change disease
Membranous nephropathy
26
What types of glomerulonephritis are associated with nephritic state?
Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis
Post-infection glomerulonephritis
27
Say whether it is associated with nephrotic syndrome or nephritic syndrome, and to what extent: *minimal change disease, membranous nephropathy, FSGS, mesangioproliferative GN, membranoprolferative GN, diffuse proliferative GN, crescentic GN*
Top 3 - non-proliferative; more protein
Bottom 3 - proliferative; more blood
28
What are the 4 types of *proliferative glomerulonephritides*?
- *Diffuse proliferative* - post-infective nephritis
- *Focal proliferative* - mesangial IgA disease
- *Focal necrotizing* (crescentic) nephritis - most advanced; aggressive injury
- *Membrano-proliferative* nephritis
29
What is the hallmark of post-infective glomerulonephritis on electron microscopy?
'sub-endothelial hump'
30
What does post-strep GN usually follow?
Follows 10-21 days after infection typically of throat or skin
31
What type of bacteria is associated with post-strep GN? Is there another component to it?
Most commonly Lancefield group A Streptococci
Genetic predisposition: HLA-DR, -DP
32
Case 1: 6 yr old boy generally unwell, dark urine, puffy face, no rashes, no oedema, BP 135/86mmHg, sore throat 2 weeks prev; what is presumptive diagnosis?
**Post-streptococcal nephritis**
33
Case 1: what would be relevant investigations? What might the results be?
Hb 130g/L; WCC 11.3 x 109
Urea 11.2mmol/L, creatinine 160umol/L (high for a 6 yr old)
Urine microscopy RBC+++, casts +
Complement: low C3
*These combined with hypertension indicate NEPHRITIC*
34
What is a urinary cast?
microscopic cylindrical structure produced by kidney and present in the urine in certain disease states; form in the distal tubule and collecting ducts then dislodge and pass into the urine
made up of white blood cells, red blood cells, kidney cells, or substances such as protein or fat - content of a cast can help tell you decide whether your kidney is healthy or abnormal
35
Treatment for post-infective glomerulonephritis?
Abx debatable !
Loop diuretic such as frusemide for oedema
Vasodilator drugs e.g. amlodipine for hypertension
36
What is the commonest cause of glomerulonephritis worldwide?
IgA nephropathy
37
What is IgA nephropathy characterised by?
IgA deposition in mesangium and mesangial proliferation
38
What demographic is IgA nephropathy most common in?
2nd and 3rd decade of life; males more commonly affected
39
What is the prognosis for IgA nephropathy?
Up to 40% can progress to end stage kidney disease
(slow disease - progresses over decades)
40
4 possible features of an IgA nephropathy presentation?
* Microscopic haematuria*
* Micrscopic hamaturia + proteinuria*
* Nephrotic syndrome* (probability of end stage KD increased)
* IgA crescentic glomerulonephritis*
41
Histology of segmental necrosis - intense glomerulus inflammation (from intense inflammation of capillaries leading to rupture)
42
Histology of crescent formation; glomerulus is circled
43
3 broad causes of crescentic glomerulonephritis?
- Auto-neutrophil cytoplasmic antibody (ANCA)-associated
- Anti-glomerular basement membrane (GBM) (10-20%)
- Others e.g. IgA vasculitis; post-infection glomerulonephritis; SLE
44
Give the types of ANCA-associated causes for crescentic glomerulonephritis (3) (hint - all ... with polyangitis
1. *Microscopic* polyangitis
2. *Granulomatosis* with polyangitis
3. *Eosinophilic granulomatosis* with polyangitis
(aggressive, v sick people, hypekalaemia, v high creatinine)
45
Give an example of an anti-GBM-associated cause of crescentic glomerulonephritis
Anti-GBM nephritis (Goodpastures syndrome)
46
Case 3: 60 yr old woman 3 month histoy of increasing tiredness, anorexia, weight loss
Physical exam - rash on both ankles + lower legs and bilateral basal crepitations; BP 150/85
Urine dipstix: protein +++ and blood ++
Serum creatinine 640umol/L
ANCA positive w MPO-ANCA of 134 units/L
What might you want to do next?
Renal biopsy
47
What might the renal biopsy from case 3 show? What is the treatment?
**Focal necrotizing glomerulonephritis**
Treatment = *high does steroids, cyclophosphamide, plasma exchange*
48
What is Anti-GBM?
Rare disease caused by circulating anti-GBM (autoantibodies which are targeted to the basement membrane, which is part of the wall of these capillary blood vessels in the kidneys and lungs; commonly affects kidneys +/- lungs)
49
What 2 things can anti-GBM present as?
- Nephritis (anti-GBM glomerulonephritis)
- Nephritis + lung haemorrhage (Goodpasture's syndrome)
50
51
What are the 2 peaks in age that people develop anti-GBM disease?
3rd decade
6th/7th decade
52
How is anti-GBM diagnosis confirmed?
By demonstrating anti-GBM antibodies in serum and kidney
53
Treatment for anti-GBM disease?
Aggressive immunosuppression: **steriod, plasma exchange and cyclophosphamide**
54
General management of crescentic glomerulonephritis is immunosuppression and prognosis is good provided treatment is started early enough, what is used in the immunosuppressive treatment (5)?
* - Corticosteroids*
* - Plasma exchange*
* - Cytotoxic e.g. cyclophosphamide*
* - B-cell e.g. rituximab*
* - Complement inhibitors*
55
Summary - proliferative glomerulonephritides - 4 points:
- Present with nephritic syndrome
- Blood on dipstix - variable proteinuria
- Can cause rapid decline in renal function leading to dialysis
- Early diagnosis and appropriate treatment
56
3 broad types of non-proliferative glomerulonephritis?
- Minimal change disease
- Focal and segmental glomerulonephritis
- Membranous nephropathy
57
Name 5 general measures for management of nephrotic syndrome
Treat oedema (salt + fluid restriction and loop diuretics)
Hypertension (RAAS-blockade)
Reduce thrombosis risk (heparin or warfarin)
Reduce infection risk (e.g. pneumococcal vaccine)
Treat dyslipidemia (e.g. statins)
58
In addition to the general measures for nephrotic syndrome; give another therapy that should be involved
Specific therapy towards cause of the non-proliferative glomerulonephritis
59
Commonest form of nephrotic syndrome in children?
Minimal Change Nephrotic Syndrome
60
Descibe onset of minimal change nephrotic syndrome?
Sudden onset of oedema - days
61
What fraction of MCNS patients relapse?
2/3rds
62
Treatment for minimal change disease (and first relapse)?
- **PREDNISOLONE** - 1mg/kg for up to 16 weeks
- Once remission acheieved - slow taper over 6 months
- Initial relapse treated with further steroid course
63
Following initial relapse, what are subsequent relapses treated with in minimal change disease?
- Cyclophosphamide (immunosuppression)
- Cyclosporin (immunosuppression)
- Tacrolimus (T-cell specific calcineurin inhibitor - similar immunosuppressive actions with cyclosporine)
- Mycophenolate mofetil (inhibits T- and B-cells - immunosuppression)
- Rituximab (monoclonal antibody - immunosuppression)
64
Prognosis for minimal change disease?
Despite relapse behaviour - prognosis now favourable
Risk of end stage KD now low
Steroids toxicity from multiple exposure
65
Case 4 - 22 yr old woman; severe oedema suddenly developed over a week
Breathless + LS chest pain
Urine dip ++++ protein
Urine protein creatinine ration 400mg/mmol
Creatinine 110mmol/l (\<110)
Serum albumin 15g/L (\>35)
Haemoglobin 154 g/L
Cholesterol 9.2 mmol/L
Pregnancy test negative
66
General measures for case 4?
Salt and fluid restrictions
Daily weights
Loop diuretic e.g. furosemide
Thromboprophylaxis e.g. low molecular weight heparin
67
As case 4 progresses what is treatment?
Predisnolone 60mg per day
(remission after 8 wks; diuretics + thromboprophylaxis stopped; predisnolone dose tapered over 6 months)
68
Is focal and segmental glomerulonephritis a single disease?
NO, rather a syndrome with multiple causes (can be primary (idiopathic) or secondary)
69
What does focal and segmental glomerulonephritis present with?
Nephrotic syndrome
70
What is the chance of focal and segmental GN progressing to end stage KD?
High
71
Histology of focal/segmental GN - podocytes are dying, as they die chance of recovery is less and less
72
Treatment for focal/segmental glomerulosclerosis?
General measures (prev described)
Trial of steroids - +ve response, even partial remission, carries better prognosis
Alternatively - immunosuppression e.g. cyclosporin, cyclophosphamide, Rituximab
73
Commonest cause of nephrotic syndrome in adults?
**Membranous nephropathy**
74
Majority of cases of membranous nephropathy occur in what?
Isolation (idiopathic)
75
2 serological markers for membranous nephropathy?
- *Anti-phospholipase A2 receptor* (PLA2R) antibody (positive in 70% of idiopathic cases)
- *Thrombospondin type 1 domain* containing 7A (THSD7A)
76
Name 4 secondary causes of membranous nephropathy
- Malignancies
- SLE
- Rheumatoid arthritis
- Drugs: NSAIDs, gol, penicillamine
77
Histology of membranous nephropathy
78
Treatment for membranous nephropathy? In what circumstances woud immunosuppression be implemented?
- General measures for at least 6 months
- Immunosuppression if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function
Cyclophosphamide and steroids (alternate months) for 6 months; Cyclosporine; Rituximab
- 1/3rd resolve spontaneously
79
Prognosis for membranous nephropathy?
Good in treated patients whose proteinuria resolves
About 25% on dialysis at 10 yrs
Can recur in renal transplants
80
Case history 6:
## Footnote
* 66 year old man presented with cough,breathlessness, and peripheral oedema.
* He smokes 20 cpd.
* Urine dip: Proteinuria ++++
* Urine protein creatinine ration 580mg/mmol.
* Serum albumin 20 g/L.
* Serum creatinine 135mmol/l
* Renal biopsy: confirms membranous nephropathy.
* CT chest/abdomen/pelvis: suggestive of lung cancer.
* Bronchoscopy and biopsy confirm squamous cell carcinoma.
* General measures for nephrotic syndrome.
* No immunesuppression.
* Partial remission following radiotherapy
81
Summary for non-proliferative glomerulonephritis - 5 points:
- Present with nephrotic syndrome
- Renal biopsy is key investigation
- Identify cause if possible
- General measures are important in all cases
- Specific treatment as appropriate
82
Summary:
* Glomerulonephritis is an important cause of end stage renal disease
* Different types of glomerulonephritis present in different ways and differ in prognosis
* Precise diagnosis depends on renal biopsy and the results influence management
