IgA Nephropathy

Background

• Also known as Berger’s disease
• Most common form of idiopathic glomerulonephritis resulting in CKD
  • Around 30-40% of patients go on to develop end-stage CKD within 20 years.
  • Usually presents in young adults and there is a slight male predominance (males tend to have a poorer prognosis)
  • Can be associated with a number of other conditions
    • e.g. Henoch Schonlein purpura; SLE; autoimmune hepatitis; ankylosing spondylitis

Pathophysiology

• Characterised by IgA- and C3- complex deposition in the glomerular mesangium
• It is uncertain as to the exact mechanism by which this occurs but patients with IgAN seem to have an raised level of circulating IgA
  • It is thought that a specific type of IgA (galactose-deficient IgA) is responsible
• As the disease progresses, several features may be seen (all contribute towards a poorer prognosis- collectively known as Oxford classification)
  • Increased mesangial cellularity
  • Segmental glomerulosclerosis
  • Endocapillary hypercellularity
  • Tubular atrophy/interstitial fibrosis

Presentation

• Usually presents with frank haematuria following an upper respiratory tract infection
  • May also present with microscopic haematuria (more common in older adults) or an AKI
• Usually this resolves in several days
  • If haematuria persists, there is usually progression to renal failure

Investigation

• Urinalysis (dipstick)
  • Usually shows protein and blood
• Urine microscopy (red cells, leukocytes and casts)
• Urinary protein and creatinine (24 hour-collection)
• Plasma IgA may be raised in around 50% of cases
• Renal biopsy will give a definitive diagnosis

Management

• Manage any hypertension – ACE inhibitors have shown to be beneficial
  • ACEIs plus Angiotensin receptor blockers may have additional benefit
• Steroids (a 6 months course of prednisolone) is thought to be protective against progression to ESKD
• Regular monitoring of renal function is important

Polyuria

Urine output of >3 litres per day.  Note that it is usually accompanied by urinary frequency, but that frequency itself may not indicate polyuria (i.e. frequently passing small vs large volumes).

Pathophysiology

• In general, polyuria can be a result of anything that causes
  • Increased water intake (polydipsia)
  • Decreased ADH (antidiuretic hormone) secretion (central diabetes insipidus)
  • Decreased peripheral ADH sensitivity (nephrogenic diabetes insipidus)
    • ADH promotes water reabsorption in the renal collecting ducts
  • Solute diuresis (most commonly seen in uncontrolled diabetes mellitus- where high glucose concentrations cause a passive diuresis)

Assessment

• History
  • Define the extent of polyuria and distinguish between urinary frequency i.e. how much urine
  • If polyuria is present, explore this
    • Onset, Duration, Progression, Triggers, Exacerbating/Alleviating factors
    • Associated symptoms- specifically thirst/drinking (polydipsia); weight changes, (also night sweats)
  • Specific things to ask about include
    • Any recent IV fluids/tube feeds; recent catheterisation/urinary obstruction; recent head trauma/surgery or stroke
      • Note patients can be polyuric following urinary obstruction
  • PMHx
    • Diabetes mellitus
    • Psychiatric disorders – on lithium treatment
    • Sickle cell disease
    • Sarcoid/amyloidosis
    • Hyperparathyroidism
    • Hypertension – on diuretics
    • Alcohol and caffeine intake
    • Smoking history
• Examination
  • General examination of
    • Blood pressure/pulse
    • Weight
    • Mucous membranes (dry?)
    • Skin (dry, pigmented lesions, ulcers/nodules)
  • Neurological/psychiatric exam (doesn’t have to be extensive but may be further explored if there is any suspicion or positive findings
    • e.g. papilloedema; visual fields etc

Red Flags

• Abrupt onset or onset in children
• Night sweats, weight loss (particularly where there is a smoking history too)
• Psychiatric disorder

Investigations

• Serum or fingerprick (BM) glucose measurement and urinalysis to rule out diabetes mellitus
• Where hyperglycaemia is absent
  • U&Es including serum Calcium
    • Hypernatraemia suggests excess water loss due to diabetes insipidus
    • Hyponatraemia suggests excess free water intake (polydipsia)
  • Urine osmolarity
    • usually low with water diuresis and high with solute diuresis
• If a diagnosis is not yet clear, a water deprivation test can be done
  • (NB only to be done as an inpatient under supervision)
    • Typically a baseline set of weight, bloods and observations are performed in the morning.  The patient is then deprived of water.  Where possible, hourly samples of urine are tested for osmolarity and sodium concentrations.  Once the patient shows signs of deprivation (i.e. orthostatic hypotension; postural tachycardia; >=5% weight loss OR if the urinary concentration does not increase by >30mOsm/kg), baseline measurements are repeated and a bolus of exogenous ADH administered.  One hour later, measurements are repeated again.
  • Interpretation
    • Normal
      • Maximal urine osmolarity after dehydration (>700mOsm/kg), and osmolarity does NOT increase >5% following ADH injection
    • Central diabetes insipidus
      • Urine osmolarity unchanged during water deprivation but concentrates following ADH administration
    • Nephrogenic/peripheral diabetes insipidus
      • Urine osmolarity shows no significant change after either water deprivation or ADH administration
    • Psychogenic polydipsia
      • Initial urine osmolarity is low (<100mOsm/kg), but urine concentration will normalise with water deprivation (essentially normal response)
  • Other tests which may be appropriate include
    • Pituitary function tests
    • Serum lithium concentration
    • Autoantibody screen

Causes

• Other causes include
  • Cushing’s syndrome/disease
  • CKD
  • Hypercalcaemia
  • Fanconi’s syndrome