QuestionSBA
QuestionChoice
The presence of casts on microscopy suggests a glomerular pathology, for which a renal biopsy would be the gold standard for diagnosis.
10015746
a
Renal biopsy
QuestionChoice
This is not yet indicated and would not give a definitive diagnosis.
10015748
c
CT abdomen and pelvis
QuestionChoice
This would be indicated to visualise the urinary bladder if red blood cells (rather than red cell casts) were seen. A cystoscopy may be paired with a US KUB or CT urogram.
10015747
b
Flexible cystoscopy
QuestionChoice
This is not indicated as an investigation for haematuria.
10015749
d
PET scan
QuestionChoice
An abdominal ultrasound may be required to image the urinary tract, however this will not reveal the definitive diagnosis of a glomerulonephritis.
10015750
e
Abdominal ultrasound
QuestionComment
Painless haematuria - bladder cancer???
40890
QuestionComment
currently, only patients older than 45 with visible haematuria not resolved by usual UTI treatment (or patients above 60 with non visible haematuria) need be referred for bladder cancer (they get a flexi cystoscopy). In this case, the patient is younger and has intermittent episodes rather than persistent haematuria so bladder cancer is further down on differentials and in any case not warranting a 2ww.  
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Ale
QuestionComment
The red cell casts point to a glomerular pathology, as red cells get squeezed through the glomerulus. Bladder cancer would not present with red cell casts
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Serotonin Xeno
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Jaundice Botox
QuestionComment
cut them all

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Chronic Gas
Concept
Chapter
## Summary 

Glomerular disease is kidney disease affecting the glomerulus. It can be classified according to its presenting clinical syndrome, eg. nephrotic or nephritic syndrome, the histological appearances, the cause or by the underlying systemic disease.

|Nephritic syndrome| Nephrotic syndrome|
|:---|:---|
|IgA nephropathy|Minimal change disease (MCD)|
|RPGN (rapidly progressive GN) (ANCA + vasculitis, anti-GBM)|Membranous GN|
|Membranoproliferative GN (MPGN)|Focal segmental glomerulosclerosis (FSGS)|
|Post-infectious GN|MPGN|
|Henoch–Schönlein purpura (HSP)/IgA vasculitis|IgA nephropathy|
|SLE | SLE|
|| Diabetes|
| |Amyloid|

Diagnosis is usually made using clinical presentation, histology obtained by a kidney biopsy and immunology.

**It is important to distinguish between nephritic and nephrotic syndrome in examination questions however it is often less clear cut in day to day practice.**

## Nephritic syndrome

### Definition
Nephritic syndrome presents with renal impairment, haematuria and non-nephrotic-range proteinuria (+/++ on the urine dipstick). There may be oliguria, with water retention and HTN.


### Causes


It is important to consider the conditions that can cause a nephritic picture. These can be remembered as:


**SHARP AIM**


- **S**LE
- **H**SP
- **A**nti-GBM disease (also known as Goodpasture's disease)
- **R**PGN
- **P**ost-infectious GN, eg. streptococcal, infective endocarditis
- **A**lport syndrome
- **I**gA nephropathy (also known as Berger's disease)
- **M**PGN

### Investigations
- Urine dipstick
- Urine micsrocopy, looking for red-cell casts
- Urine PCR
- FBC, U&Es, LFT, bone profile, CRP, ESR
- Nephritic screen: ANA (inc. dsDNA), ANCA, anti-GBM, C3/C4
- USS kidneys, ureters and bladder (KUB)
- Kidney biopsy

## IgA nephropathy (IgAN)


### Definition


A type of GN characterised by IgA deposition in the mesangium. 

This is the most common type of GN worldwide.


### Cause


- The pathophysiology is not completely understood
- It is thought there is an increased propensity to form IgA immune complexes that are lodged in the mesangium of the glomerulus
- IgA deposition combined with activation of the complement pathway and cytokine release leads to glomerular injury


### Clinical features


- Typically, patients present with recurrent gross or microscopic haematuria following **12–72 h** of an upper respiratory-tract infection or GI infection
- It is more common in patients aged 20–30
- Mild proteinuria may be present
- HTN may be present
- Rare cases may present with a nephrotic syndrome, or a rapidly progressive GN where they rapidly progress to acute renal failure
- It can be associated with HSP/IgA vasculitis, chronic liver disease, inflammatory bowel disease (IBD) and skin and joint disorders, eg. psoriasis


### Investigations


- First-line investigation includes a urinalysis and MC&S:
	- Urinalysis is typically positive for blood ± protein; it is rare for patients to present with nephrotic-range proteinuria
	- Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus
- The gold-standard method for diagnosis is renal biopsy:
	- This shows diffuse mesiangial IgA immune complex deposition
- Serum IgA is elevated in approximately 50% of patients


### IgA nephropathy *vs* post-streptococcal GN (PSGN)


IgAN can be differentiated from PSGN by the following features:

- IgAN occurs 1–2 days post-infection *vs* 1–3 weeks post-infection in PSGN.
- Renal biopsy in IgAN shows IgA immune-complex deposits *vs* IgG immune-complex deposits in PSGN.


### Management

The mainstay of treatment is supportive and aimed at reducing cardiovascular risk:

- Dietary salt restriction
- Treatment of proteinuria (>0.5 g/day) with an ACE-i/ARB
- Treatment of HTN

Patients are risk stratified into those who are at low risk of progression to CKD and ESKD and those at high risk:

- Those at high risk of progression are considered for treatment with corticosteroids.
- Immunosuppresion should be offered for those who present with an RPGN.

### Prognosis

Progression to ESKD occurs in ~30% of patients after 10–25 years from diagnosis.

## Further reading and references
[Patient UK: Glomerulonephritis](https://patient.info/doctor/glomerulonephritis-pro)

## Post-streptococcal glomerulonephritis (PSGN)

### Definition


PSGN is a type of immune-complex-mediated GN that can occur 1–3 weeks after a streptococcal upper respiratory-tract infection. It is more common in children than adults.

GN can occur after other types of bacterial infection; however, PSGN or infective endocarditis are the most commonly encountered causes.


### Cause


- It is caused by certain strains of group A β-haemolytic streptococci.
- Pathogenesis is not fully understood but main theories suggest that there is immune-complex deposition, neutrophil infiltration and complement activation in the glomerulus causing inflammation and/or proliferation.


### Clinical features


- Patients typically present with sudden onset of haematuria, oliguria, HTN and/or oedema 1–3 weeks post-infection
- Patients may also be asymptomatic with microscopic haematuria

### Investigations


- First-line investigation includes a urinalysis and MC&S:
	- Urinalysis is typically positive for blood ± protein
	- Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus
- An FBC may show raised white cells, suggestive of an infective process
- U&Es often show an AKI
- Immunoglobulins, complement (low C3 levels commonly found) and autoantibodies (such as raised anti-streptolysin titre, raised DNAse B titre) can help support the diagnosis
- Blood cultures are indicated in patients with fever
- The gold-standard method for diagnosis in adults is a renal biopsy:
	- The classical finding is subepithelial 'humps' on electron microscopy

### IgA nephropathy *vs* post-streptococcal glomerulonephritis


PSGN can be differentiated from IgAN by the following features:

- PSGN occurs 1–3 weeks post-infection *vs* 1–2 days post-infection in **IgAN**<!---Any reason for these double asterisks?-->
- Renal biopsy in PSGN shows IgG immune-complex deposits in PSGN *vs* IgA immune-complex deposits in IgAN


### Management


The infective course is usually self-limiting, and management of AKI is as per any cause of AKI.


### Prognosis


Prognosis following resolution of AKI is good; however, some patients may go on to develop CKD.

## Infection-associated glomerulonephritis

Infection-associated GN is an acute nephritis associated with infection.

| Bacterial | Viral | Fungal | Parasitic |
|:---|:---|:---|:---|
| Streptococcal (PSGN) | Hepatitis B | Candida | Malaria |
| Staphylococcal | EBV, CMV | | Toxoplasmosis |
| Pneumococcal | Influenza, mumps, rubella | | Schistosomiasis | 

## Membranoproliferative glomerulonephritis (MPGN)

### Definition

MPGN is also known as mesangiocapillary GN (MCGN); it is a term used to describe the histopathological picture on kidney biopsy.

### Cause

There are many causes; however, the important ones to be aware of for the MRCP exams are:

- Hepatitis C
- Mixed cryoglobulinaemia
- Monoclonal gammopathies

It is thought to be caused by immune-complex deposition and complement activation.

### Clinical features

Patients more commonly present with a nephritic rather than nephrotic picture and AKI. The clue to the diagnosis will be the underlying aetiology, eg. hepatitis C.

### Investigations

- First-line investigations include urinalysis and MC&S:
	- Urinalysis is typically positive for blood ± protein
	- Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus
- An acute renal screen should be sent which may identify the underlying cause
- The gold-standard method for diagnosis in adults is a renal biopsy:
	- The classical finding is a 'double contour' of the basement membrane

### Management

General measures include supportive measures are aimed at reducing cardiovascular risk:

- Dietary salt restriction
- Treatment of proteinuria (>0.5 g/d) with ACE-i/ARB
- Treatment of HTN

If there is an underlying cause, eg. HCV, it should be treated appropriately. In some cases of MPGN, treatment with immunosuppression might be considered.

### Prognosis

Around 50% of patients progress to ESKD by 10 years.

## Anti-glomerular basement membrane (anti-GBM) disease 

Anti-GBM disease is a rare cause of RPGN; it used to be known as Goodpasture syndrome.

### Cause


Anti-GBM disease is caused by antibodies to the non-collagenous domain (NC1) of the ⍺3 chain of type IV collagen.


These antibodies are directed against antigens found on the GBM in the kidneys and in the lung alveoli, leading to the presentation with pulmonary–renal syndrome.

### Clinical features

- Haemoptysis and pulmonary haemorrhage
- AKI, often severe and rapidly progressive, leading to renal failure
- It is more common in males
- There are two peaks in age of presentation: 20–30 years and 60–70 years

### Investigations

- Urinalysis and MC&S:
	- Urinalysis is typically positive for blood ± protein
	- Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus
- U&Es to assess degree of AKI and whether dialysis is indicated
- pH to assess degree of acidosis and whether dialysis is indicated
- CXR/CT to identify and assess the degree of pulmonary haemorrhage
- An acute renal screen to identify the cause:
	- **anti-GBM** should be specifically requested for patients presenting with pulmonary–renal syndrome; this will be positive
	- ANCA may be positive; the patient should be managed per anti-GBM
- Renal biopsy is the gold standard for diagnosis:
	- this will show focal and segmental necrotising crescents and linear IgG standing along the basement membrane


### Management


The pillars of therapy in anti-GBM disease involve:


1. Removoval of the circulating antibody:
	- achieved with plasma exchange which removes the pathogenic circulating antibodies. 	
2. Immunosuppression to stop further production of antibodies:
	- normally achieved with high-dose oral prednisolone and cyclophosphamide.
	- relapse of the disease is very rare and maintenance immunosuppression is not usually indicated.

### Prognosis


- If untreated the disease is fatal
- Patients who present with severe AKI and require dialysis have a very poor renal prognosis

### References and further reading
[Vasculitis UK: Anti-GBM](https://www.vasculitis.org.uk/about-vasculitis/anti-gbm-goodpastures-disease)

## ANCA-associated vasculitis (AAV)

AAV includes granulomatosis with polyangitis (GPA), eosinophilic granulomatosis with polyangitis (EGPA) and microscopic polyangitis (GPA). They are pulmonary–renal syndromes associated with positive ANCAs.

#### ANCA

There are two types of circulating ANCAs: cANCA and pANCA

- cANCA is named as such for producing cytoplasmic staining patterns
	- **cANCA** reacts with **anti-proteinase-3 (PR3)** antigens in the cytoplasm of the neutrophils
- pANCA is so called for producing perinuclear staining patterns
	- **pANCA** reacts with **myeloperoxidase (MPO)** in the lysosomes of monocytes

#### Granulomatosis with polyangiitis (GPA)


- Also known as Wegners granulomatosis
- The majority of patients with GPA are **cANCA positive (anti-PR3)**
- GPA is characterised by upper respiratory-tract symptoms, pulmonary haemorrhage (70%), RPGN and signs of systemic vasculitis
- Kidney biopsy shows a focal and segmental necrotising GN which is pauci-immune

### Eosinophilic granulomatosis with polyangiitis (EGPA)


- Also known as Churg Strauss
- The majority of patients with EGPA are **pANCA positive (anti-MPO)**
- EGPA is characterised by allergic asthma, rhinitis and eosinophilia
- Approximately 30% have renal involvement; 50% of these present with an RPGN
- Kidney biopsy shows a focal and segmental necrotising GN with eosinophilic infiltration


#### Microscopic polyangiitis (MPA)


- The majority of patients with MPA are **pANCA positive (anti-MPO)**
- MPA is characterised by pulmonary haemorrhage (30%), RPGN and signs of systemic vasculitis
- Kidney biopsy shows a focal and segmental necrotising GN which is pauci-immune

### Management

Management is with immunosuppression and consists of an induction and maintenance phase.

The indications for dialysis are as for other causes of AKI.

### References and further reading

[Vasculitis UK: GPA](https://www.vasculitis.org.uk/about-vasculitis/gpa-granulomatosis-with-polyangiitis)  
[Vasculitis UK: MPA](https://www.vasculitis.org.uk/about-vasculitis/microscopic-polyangiitis)  
[Vssculitis UK: EGPA](https://www.vasculitis.org.uk/about-vasculitis/churg-strauss-syndrome)


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1116
Glomerulonephritis
Topic
33
Nephrology
15693
Red cell casts on urine microscopy suggest a glomerular condition
Presentation
291
Haematuria
UkmlaTopic
3
Cancer
Presentation
293
Haematuria
UkmlaTopic
12
General practice and primary healthcare
Presentation
294
Haematuria
UkmlaTopic
13
Infection
Presentation
295
Haematuria
UkmlaTopic
22
Renal and urology
Presentation
296
Haematuria
UkmlaTopic
25
Surgery
A 32-year-old gentleman has three episodes of red urine that have now resolved. A urine microscopy shows red cell casts, with no white cells and no bacteria seen.

What is the single most appropriate investigation for definitive diagnosis?
a