Nephritic Sydnrome: IgA Nephropathy (Beuger Disease)

Question 1

Definition

Answer 1

The most common primary glomerulonephritis
It is the presence of IgA immune complexes in the mesangium of the glomerulus, resulting in nephritic syndrome and progressing to end-stage renal disease (ESRD) over many decades if untreated.
* All nephritic syndromes examples of Type 3 hypersensitivity reaction with the exception of Goodpastures syndrome = T2 *

Question 2

Epidemiology

Answer 2

Adolescents and middle age: 80% of cases are diagnosed between the ages of 16 and 35
Male gender
Ethnicity: IgA nephropathy is more common in Asian populations than Caucasian populations

Question 3

Risk factors

Answer 3

Preceding URTI or gastroenteritis: infections of the mucosal tracts act as a trigger for the production of IgA, leading to subsequent deposition
HIV
Family history: an autosomal dominant familial form of IgA nephropathy exists
Presence of other autoimmune conditions: linked to conditions such as HSP, SLE, coeliac disease and alcoholic liver disease

Question 4

Pathophysiology

Answer 4

The deposition of IgA immune complexes in the mesangium causes mesangial proliferative glomerulonephritis due to a type III hypersensitivity reaction. This process also involves activation of the alternative complement pathway (e.g. C3 conversion to C3a and C3b), which triggers glomerular injury. The is significant pathophysiological overlap with Henoch-Schönlein purpura (HSP).
Episodes of IgA nephropathy tend to develop following an infection of the mucosal lining, for example following an upper respiratory tract infection (URTI) or, less commonly, gastroenteritis. This is likely due to an increased production of IgA, with subsequent IgG recognition and deposition in the kidneys

Question 5

Signs

Answer 5

Haematuria:
- Macroscopic: particularly in younger patients
- Microscopic: particularly in older patients
Oedema: due to proteinuria
Oliguria
Cervical lymphadenopathy: suggests an URTI as a recent trigger
HTN

Question 6

Symptoms

Answer 6

• symptoms seen 1-2 days post URTI compared to post-strep GN which is 1-2 weeks post infection*
  Pink, red, or coke tinged urine (haematuria)
  Foamy urine (proteinuria)
  Sore throat: suggest an URTI as a recent trigger (common)
  Loose stools and abdominal discomfort: suggest gastroenteritis as a recent trigger

Question 7

Investigations

Answer 7

Urine dipstick:
- blood
- little protein (<3g per 24 hours anymore is nephrotic)
U + E: baseline renal function assessment
C3 + C4 levels:
- C4 = normal as the classical complement pathway is not activated
- C3 can either be low or normal depending on the extent of alternative pathway activation. There is some evidence to suggest that greater C3 depletion is associated with a poorer prognosis
GOLD STANDARD: Renal biopsy = mesangial hypercellularity = positive immunofluorescence for IgA + C3

Question 8

Management

Answer 8

First line: ACE-inhibitor/ARB: immediately offer either medication if protein: creatinine ratio (PCR) is >100 mg/mmol. Consider offering if PCR is 50-100 mg/mmol
Corticosteroids: offer a 6-month trial if there is persistent proteinuria despite 3-6 months of an ACE inhibitor or ARB.
Statins: control of high cholesterol has been shown to slow kidney damage.
Omega-3 fatty acids: available in dietary fish oil, these supplements reduce glomerular inflammation; offer if there is persistent proteinuria despite 3-6 months of an ACE inhibitor or ARB

Question 9

Complications

Answer 9

HTN,
AKI,
CKD,
Rapidly progressive glomerulonephritis
Nephrotic syndrome
Henoch-Schoenlein Purpura