Glomerulonephritis and Nephritic Syndrome

Question 1

What is nephritic syndrome ?

Answer 1

Nephritic syndrome is a collection of conditions characterised by glomerular inflammation, presenting with
* Proteinuria (<3.5g/24hrs)
* Microscopic haematuria
* Rise in serum creatinine
* +/- Hypertension

Question 2

What is the pathogenesis of nephritic syndrome ?

Answer 2

It is an immune mediated Injury to the glomerulus which disrupts the
filtration process, and results in
destruction of the glomerular basement
membrane. It can also be due to infections and systemic conditions.

Question 3

What is IgA nephropathy (Berger Disease)?

Answer 3

It is the most common primary GN in high income countries. It classically presents as gross haematuria after an URTI,GI infection or strenuous exercise. It is characterised by IgA deposition in mesangium leading to local inflammatory response.

Question 4

What are the immunofluorescence findings in Berger’s disease ?

Answer 4

On immunofluorescence, will see IgA, C3 and
mesangial proliferation.

Question 5

What is Henoch-Schonlein purpura ?

Answer 5

It is a systemic form of IgA vasculitis resulting in a purpuric rash in the extensors, polyarthritis, scrotal pain, GI bleeds and nephritis.

Question 6

What is PSGN ?

Answer 6

It Occurs 1-2 weeks after group A
Beta Hemolytic Streptococcal
Infection. It presents as Tea or Cola Coloured Urine. It is Usually, self-limiting
May lead to rapidly progressive
glomerulonephritis (RPGN) and
renal failure.

Question 7

What are the diagnostic work-up in PSGN ?

Answer 7

*Positive Antistreptococcal antibodies
*Biopsy

Question 8

What is ANCA associated vasculitis relapse risk relative to antibodies ?

Answer 8

It may also be associated with PR3 and MPO antibodies. It has a seasonal variation in incidence. PR3-ANCA at diagnosis have a higher long term relapse risk as compared to the MPO-ANCA at diagnosis.

Question 9

What is the clinical presentation of ANCA vasculitis ?

Answer 9

The patients presents with evidence of Nephritic syndromes and Constitutional symptoms. There may also be ocular and ENT symptoms. However, the main small vessel vasculitis findings are vasculitic rashes and pulmonary hemorragh related hemoptysis, cough and dyspnoea.

Question 10

What is anti-GBM disease ?

Answer 10

It is relatively uncommon with two peaks across the life 20 to 30 years and 60 to 70 years. It is also a rapidly progressive renal-pulmonary syndrome. The nephrotic symptoms progress to anuria within days to weeks. This can rapidly progress to ESRD if not treated rapidly.

Question 11

What are the laboratory findings in anti-GBM disease?

Answer 11

Antibodies to Type IV Collagen in the glomerular basement membrane (anti-GBM Abs)

Question 12

What is Membranoproliferative glomerulonephritis MPGN?

Answer 12

MPGN is a histologic lesion and not a specific
disease entity. It presents with immune complex deposition and complement system dysregulation leading to inflammation and thickening of the glomerular basement membrane. Biopsy will show large glomeruli and mesangial proliferation.

Question 13

What is the microscopic hallmark of MPGN ?

Answer 13

“Tramline” double-basement membrane on
microscopy

Question 14

What is RPGN ?

Answer 14

Any aggressive glomerulonephritis rapidly worsening to renal failure. It is Characterised by the proliferation of parietal epithelial cells and
macrophages in Bowman’s capsule.

Question 15

What are the causes of RPGN ?

Answer 15

 Small vessel/ANCA Vasculitis
 Lupus Nephritis
 Anti-GBM Disease
 Other glomerulonephritis may transform to RPGN (IGA, Membranoproliferative)

Question 16

What are the general symptoms of nephritic syndromes ?

Answer 16

Presentation dependent on underlying aetiology.
* Fatigue/Malaise
* Haematuria
* Decreased urine output (glomerular
destruction)
* Low grade pyrexia (Infectious/Autoimmune)
* Features of vasculitis (Purpuric rash,
Haemoptysis)
* Symptoms of underlying condition (e.g., SLE)

Question 17

What are the urine work-ups in nephritic syndrome ?

Answer 17

• Urine dipstick
  *Microscopy & Culture to look for Acanthocytes/ Red Cell casts which indicates active disease or infections.
  *Albumin/Creatinine ratio & Protein/Creatinine ratio to quantify degree of damage.

Question 18

What are the routine blood works in nephritic syndrome ?

Answer 18

FBC - Anaemia, Infection, Eosinophilia
U&E/Bone profile – GFR, Electrolyte disturbance
Albumin
CRP - Active inflammation

Question 19

What are the Immunological tests in nephritic syndromes ?

Answer 19

ANA, ANCA, Anti-GBM, ANA, ENA, Anti-dsDNA,
Complement (C3, C4), Rheumatoid Factor
HIV/HBV/HCV, ASOT
Immunoglobulins & serum protein electrophoresis

Question 20

What are the PRINCIPLES OF MANAGEMENT in nephritic syndrome ?

Answer 20

• Blood pressure control- Target blood pressure <130/80, Diuretics/ACEI/ARB
• Correct volume status by restrict water and salt intake, may require diuretics, monitor with daily weight.
• Treatment depends on the underlying etiology and severity of the disease
• Initial goal is to to achieve remission (induction) before altering treatment to
  maintain remission (maintenance)

Question 21

What are the Immunosuppressive medications commonly used in nephritic syndromes ?

Answer 21

• Corticosteroids (methylprednisolone/prednisolone)
• Cyclophosphamide
• Monoclonal antibody (Rituximab anti-CD20)

Question 22

What is nephrotic syndrome ?

Answer 22

Nephrotic syndrome is a triad of:
1) Heavy Proteinuria – >3.5g/24 hours (PCR >300mg/mmol, ACR >250mg/mmol).
2) Hypalbuminaemia serum albumin < 35g/L) – usually serum albumin is<30g/L.
3) Oedema – the presence of fluid in the extracellular spaces and bodily
compartments.

Question 23

What is the pathophysiology of nephrotic syndrome ?

Answer 23

Injury to the podocytes causes podocyte foot process effacement and detachment. Which causes protein leakage into ultra filtrate. Leading to foamy urine formation.

Question 24

What are the symptoms of nephrotic syndrome ?

Answer 24

Foamy urine and pitting edema, infections and thrombotic complications.

Question 25

What are the causes of nephrotic syndrome ?

Answer 25

*Minimal-change nephropathy(70-90% children and 10-15%in adult)
* Membranous nephropathy (30% in adult)
* Focal glomerulosclerosis (15%inadult)
* Membranoproliferative glomerulonephritis .

Question 26

What are the secondary causes of nephrotic syndrome?

Answer 26

• Diabetes mellitus
• Systemic Lupus erythematosus
• Amyloidosis and paraproteinemia
• Viral infections (e.g., hepatitis B, hepatitis C, HIV)

Question 27

What is the presentation of Minimal Change Disease?

Answer 27

It usually presents with nephrotic range proteinuria. Patients can be asymptomatic with or without edema which can be anywhere such as scrotal edema. They may also have HTN and hyperlipidemia. It is more common in kids.

Question 28

What is the pathology of minimal change disease ?

Answer 28

Normal appearance by light microscopy –
Diffuse foot process effacement.

Question 29

What is the tx of minimal change disease ?

Answer 29

*Corticosteroids (high dose) X 4 weeks with
slow taper.
* Treat hyperlipidemia and HTN.
*Most respond within 8 weeks, however relapses are frequent.

Question 30

What is Membranous Nephropathy?

Answer 30

It is the Most common cause of nephrotic
syndrome in adults.

Question 31

What is the marker of primary membranous nephropathy ?

Answer 31

Anti PLA2R antibodies

Question 32

What is the secondary causes of membranous nephropathy ?

Answer 32

• Infections (HBV/HCV)
• Autoimmune – SLE, RhA
• Medications – NSAIDs, GOLD

Question 33

What is the preferred Tx in membranous nephropathy ?

Answer 33

• Prednisolone and other
  immunosuppressants
• Diuretics for volume overload
• Statins for high cholesterol
• ACEI if HTN
• DVT prophylaxsis if in hosptial

Question 34

What is Focal Segmental Glomerulosclerosis?

Answer 34

It is mostly idiopathic, but can be seen in Heroin users and HIV patients. It is the Most common cause of nephrotic syndrome in adults,
especially in African American
and Hispanic populations.

Question 35

What is the diagnostic work-up and Tx ?

Answer 35

• Biopsy
• Steroids and other
  immunosuppressants

Question 36

What are the cardinal symptoms of nephrotic syndrome ?

Answer 36

• Oedema – onset can be both rapid
  and severe.
• Frothy urine.
• Malaise and fatigue.

Question 37

What is the pattern of oedema in nephrotic syndrome ?

Answer 37

 Typically starts with periorbital oedema
 Peripheral oedema (pitting)
 Pleural effusion
 Pericardial effusion
 Ascites
 In severe cases, anasarca

Question 38

What are the work-ups in nephrotic syndrome ?

Answer 38

*24-hour urine collection for measurement of protein excretion. Excretion >3.5g/24 hours (normal is approximately 0.15g/24 hours).
* Urine protein : creatinine ratio (PCR): alternative to 24-hour urine collection. PCR > 300mg/mmol (normal is 2.5 in men and 3.5mg/mmol in women).
* Urine albumin : creatinine ratio (ACR) : alternative to 24-hour urine collection. ACR >250mg/mmol (normal is 15mg/mmol).
* Anti-PLA2Receptor antibodies : Positive in Membranous nephropathy in 70% of
cases.
* Renal biopsy: Biopsy is useful for: confirming the diagnosis
histologically, prognostication, and to inform management decisions.

Question 39

What is the management of minimal change disease ?

Answer 39

Corticosteroids (highly responsive) – Prednisolone 1mg/kg for 4 – 16 weeks depending upon response.
Immunosuppression in case of frequent relapse – cyclophosphamide.

Question 40

What is the indication of malignancy in secondary membranous nephropathy?

Answer 40

elderly presenting with Anti-PLA2 negative disease require CTPA to rule out malignancy.

Question 41

What is the management of Membranous nephropathy?

Answer 41

Initial management: conservative therapy including an RAAS inhibitor (i.e., ACEI or ARB)
Consider immunosuppressive therapy for severe or refractory disease.
Prednisone AND cyclophosphamide
Alternatives: cyclosporine, tacrolimus, OR rituximab

Question 42

when is immunosupression indicated in the management of MPGN ?

Answer 42

Immunosuppression is indicated if there is declining renal function.

Question 43

What is the management of FSGS ?

Answer 43

Immunosuppression is indicated in primary disease only, inconjunction with ACE/ARB. If response to corticosteroids is poor, calcineurin inhibitors like tacrolimus are
indicated as 2nd – line agents

Question 44

What is the management of diabetic nephropathy ?

Answer 44

*Strict glycaemic control
*RAAS inhibition (e.g., ACEI or ARB)
*Optimization of blood pressure control
*Close surveillance and timely referral to renal replacement therapy if ESRD is anticipated

Question 45

What is the management of Amyloid nephropathy?

Answer 45

*AL amyloidosis: treatment of multiple myeloma or other plasma cell dyscrasia
*AA amyloidosis: treatment of underlying inflammatory condition

Question 46

What is the management of Lupus nephritis ?

Answer 46

*Consult a nephrologist.
*Induction and maintenance therapy is generally indicated in patients with class III or IV lupusnephritis.
*All patients should receive standard therapy for lupus and individualized management of CKD.