Urinary 15&16 - Glomerulonephritis & Diabetic Neuropathy

Question 1

4 features of glomerulonephritis

Definition
Damaged Structures x4
Classification x4
Causes x2

Answer 1

1. ) Definition - inflammation of glomeruli
   - often involves the immune systen
2. ) Damaged Structures - one or more can be affected
   - capillary endothelium, glomerular basement membrane (GBM), mesangial cells, podocytes
3. ) Classification - depends on several factors:
   - clinical presentaion, histological appearance, diagnosis, primary/secondary
4. ) Causes - primary or secondary
   - primary causes only affects the kidneys
   - secondary causes affects the whole body

Question 2

Nephrotic Syndrome

Aetiology
Clinical Triad
Investigations
Management

Answer 2

1.) Aetiology - podocyte damage leading to glomerular charge-barrier disruption causing protein leakage

2. ) Clinical Triad
   - proteinuria: >3g/24h in urine OR urine PCR >300
   - hypoalbuminaemia: <30 serum albumin
   - oedema: periorbital and bilateral pitting leg swelling
3. ) Investigations
   - bloods: FBC, U+Es, albumin, HbA1c
   - urinalysis, 24hr urine collection or urinary PCR
   - USS guided renal biopsy to confirm the type
4. ) Management
   - fluid overload: diuretics, salt and water restriction
   - proteinuria: ACEi or ARBs, also control BP
   - minimal change disease: steroids, if no improvement, must be focal segmental glomerulosclerosis instead
   - treat potential complications

Question 3

Causes of Nephrotic Syndrome

Minimal Change Disease
Membranous Nephropathy
Focal Segmental Glomerulosclerosis

Answer 3

1. ) Minimal Change Disease - affects mainly children
   - reversible so usually no progression to renal failure
   - can be fully treated with steroids
   - can advance to FSGS
2. ) Membranous Nephropathy - affects mainly adults
   - can be primary (autoimmune) or secondary (caused by other diseases e.g. lymphoma)
3. ) Focal Segmental Glomerulosclerosis (FSGS) - can affect children and adults
   - scarring of small sections of each glomeruli
   - circulating factor damaging podocytes
   - can progress to renal failure

Question 4

Complications of Nephrotic Syndrome

Infection
Thromboembolism
Hyperlipidaemia
Hypocalcaemia
AKI/Worsening CKD

Answer 4

1.) Infection - due to loss of immunoglobulins

2. ) Thromboembolism - loss of ATIII, plasminogen
   - stroke, DVT, renal vein thrombosis
   - prophylactic dalteparin if albumin <20
3. ) Hyperlipidaemia - altered lipoprotein metabolism
   - can start patients on a statin

4.) Hypocalcemia - loss of vitamin D

5. ) AKI/Worsening CKD
   - may require renal replacement therapy if severe

Question 5

Nephritic Syndrome

Aetiology
Clinical Features
Investigations
Management

Answer 5

1.) Aetiology - disruption of endothelium results in inflammatory response causing damage to the glomerular basement membrane

2. ) Clinical Features
   - haematuria +/- proteinuria +/- mild-moderate oedema
   - proteinuria <3g/24hrs or urine PCR <300
   - AKI (↓GFR): rapidly progressive GN
   - hypertension
3. ) Investigations
   - bloods: FBC, U+Es, clotting, PSA
   - urinalysis, 24hr urine collection or urine PCR
   - exclude infection and malignancy for haematuria
   - renal biopsy to confirm diagnosis/type
4. ) Management
   - fluid overload: diuretics, salt and water restriction
   - proteinuria: ACEi or ARBs, also control BP
   - immunosuppressive therapy depending on specific cause of GN, decided by renal +/- resp + rheum
   - plasma exchange for anti-GM or ANCA vasculitis
   - dialysis in severe AKI due to RPGN

Question 6

Causes of Nephritic Syndrome

Anti-GBM Disease (Goodpasture's)
ANCA-associated Vasculitis 
SLE Nephritis
IgA Nephropathy/Henoch-Schonlein Purpura
Post Streptococcal/Infectious

Answer 6

1. ) Anti-GBM Disease- antibodies to type 4 collagen in GBM and alveolar basement membrane (rarer)
   - pulmonary haemorrhage (haemoptysis) more likely w/ smokers (pre-existing damage to alveolar endothelium)
   - can lead to RPGN
   - anti-GBM antibodies, pulmonary infiltration on CXR
2. ) ANCA-associated Vasculitis - small vessel vasculitis
   - granulomatosis w/ polyangiitis (GPA), microscopic polyangiitis (MPA), eosonophilic GPA (Churg-Strauss)
   - pulmonary and nasopharyngeal involvement –> haemoptysis, nasal ulcers/polyps
   - eosinophilic has atopic features + purpura and peripheral neuropathy aswell as eosinophilia
   - all have positive ANCA antibodies
3. ) SLE Nephritis - can be nephritic or nephrotic
   - +ve ANA and anti-dsDNA antibodies
4. ) IgA Nephropathy/Vasculitis/HSP - disease of the skin and mucous membranes
   - visible haematuria associated w/ URT or GI infection
   - causes purpura rashes (bleeding underneath the skin)
   - also often w/ joint pain and abdominal pain
5. ) Post-Streptococcal GN (Post-Infectious)
   - weeks after group A ß-haemolytic strep e.g. post tonsillitis/pharyngitis, impetigo/cellulitis
   - low serum C3, + anti-streptococcal antibodies
   - biopsy: immune complex deposition (IgG, IgM, C3)
   - self-limiting, ACEi/ARB, low sodium diet

Question 7

Complication and risk factors (8) of diabetic nephropathy

Answer 7

1.) Complication - commonest cause of end stage renal disease (ESRD)

2. ) Risk Factors - age, ethnicity, genetics, smoking
   - hypertension, hyperglycaemia, duration of diabetes, high level of hyperfiltration

Question 8

5 pathological changes in diabetic nephropathy

Answer 8

1. ) Hyperfiltration and Hypertrophy - occurs early
   - related to hyperglycaemia
   - glomerular hypertension causes increase in GFR
2. ) GBM Thickening - increases pore size
3. ) Mesangial Expansion - raises intraglomerular pressure
4. ) Podocyte Injury
5. ) Glomerulosclerosis - scarring of the glomerulus and the small blood vessels
   - hyaline in arterioles (arteriolosclerosis)

Question 9

5 stages of diabetic nephropathy

Hyperfiltration and Hypertrophy
Latent Stage
Microalbuminuria
Overt Proteinuria
ESRD

Answer 9

1. ) Hyperfiltration and Hypertrophy of Kidneys
   - increased GFR
2. ) Latent Stage
   - normal albuminuria
   - GBM thickening and mesangial expansion
3. ) Microalbuminuria - moderate increase in albuminuria
   - high urine albumin:creatinine ratio
   - GBM thickening and mesangial expansion
   - podocyte changes
   - GFR returns to normal
   - potentially reversible at this stage
4. ) Overt Proteinuria - severely increased albuminuria
   - diffuse histopathological changes
   - worsening systemic hypertension
   - falling GFR
   - irreversible, can only be slowed

5.) End Stage Renal Disease

Question 10

Management of diabetic nephropathy

Primary Prevention
Managing Microalbuminuria and Proteinuria x5

Answer 10

1. ) Primary Prevention - tight glycaemic and BP control
   - can reverse initial hyperfiltration and delay worsening
   - doesn’t slow GFR loss in overt proteinuria
2. ) Managing Microalbuminuria and Proteinuria
   - RAAS inhibition, tight BP control, statin therapy, CV risk management, moderate protein intake