IgA Nephropathy


  • 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


  • 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


  • 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


  • 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


  • 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


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).


  • 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)


  • 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


  • 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



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

Examination of the Renal System

NB Signs of kidney disease are quite non-specific and are usually the result of chronic disease.  In the acute setting, U&Es often describe a more specific representation of kidney function.

  • WIPE (wash hands, introduce self, check patient details, explain and gain consent)
  • General Inspection
    • Is the patient well? Are they breathless? Are they cachexic?  Are they drowsy or confused?
    • Look at the patient’s hands-
      • Do they have a flapping tremor (may indicate hyperuraemia)
      • Is there leukonychia (hypoalbuminaemia in nephrotic syndrome); koilonychia (anaemia associated with nephritic syndrome)?
      • Is the skin turgor normal? (fluid status)
    • Look at the patient’s skin
      • Is it dry? (CKD can cause sweat gland atrophy); any hyperpigmentation or yellow/sallow skin; petechiae/ecchymoses; excoriation (itching due to hyperuraemia)
    • Is there an AV-fistula in the patient’s arm?
    • Check the pulse
    • Check BP (ideally postural but lying only may suffice)
    • Check JVP (fluid overload in nephrotic syndrome)
    • Look at the patient’s face-
      • Are there any signs of uraemia (yellow tinge); periorbital oedema (nephritic syndrome); pallor; corneal arcus/xantholasma (hyperlipidaemia in nephrotic syndrome); dry mucous membranes; butterfly rash (autoimmune disease- SLE)
    • Look at the patients legs for any signs of oedema
  • Chest
    • Examine the chest for any signs of pulmonary oedema (very rarely raised uraemia can also cause pericarditis- so listen to the heart too)
  • Abdomen
    • Inspect for any scars (transplant/operations); drains; abnormalities; ascites
    • Palpate the abdomen as you would for a full abdominal examination i.e. superficial/deep for 9 quadrants; palpate for organomegaly
      • Particularly important to ballot kidneys (with your left hand under the flank, ask the patient to breathe out and press up into the renal angle with left hand whilst pressing down with the right hand; ask the patient to breathe in- as they do you may be able to feel the kidney between your hands and can ballot it with the left)
      • Also important to examine for ascites and any shifting dullness (see abdo exam)
      • Auscultate for renal bruits as well as bowel sounds

Cystic diseases of the Kidney

NB Renal cysts are common, especially in older patients.  They are usually incidental findings and rarely require any management (they can occasionally cause pain and haematuria if they rupture)

Adult Polycystic Kidney Disease

Background / Epidemiology

  • Autosomal dominant condition caused by mutations in the PKD1 gene (85%) or PKD2 gene (15%)
    • Most patients with PKD1 mutations cause end stage renal disease and usually presents at around age 55
    • Only a minority of patients with PKD2 mutations end up with renal failure; they also usually present later at around 70 years.
  • Common- incidence of around 1 in 1000; accounts for 10-15% of patients on dialysis


  • Hypertension may be an early sign (~age 20)
  • Vague abdominal/loin discomfort with a palpable mass (often bilateral)
    • Acute pain or renal colic may be due to cyst rupture
  • Haematuria (rarely proteinuria)- usually gross episodes which resolve spontaneously, although microscopic haematuria usually remains
  • Urinary tract/cyst infections
  • Chronic kidney disease
  • Extrarenal manifestations
    • About 30% also have liver cysts although impairment of function is rare (may have hepatomegaly
    • About 10% have cerebral berry aneurysms and are at risk of subarachnoid haemorrhage (probably restricted to certain mutations)
    • Mitral and aortic regurgitation and LV hypertrophy is frequent but usually mild
    • Patients may have features of polycythaemia (increased EPO production)


  • USS of the kidney is usually diagnostic
    • FBC, U&Es and LFTs should be done routinely to check renal and hepatic function


  • As with CKD- management of cardiovascular risk factors is important e.g. hypertension control
  • Unless they cause severe pain or infection, the kidneys are usually not removed.
  • If kidney function deteriorates, patients usually do well on dialysis.

Medullary Sponge Kidney

  • Cystic disease of the papillary collecting ducts
  • Not seem to be genetic (aetiology unknown)
  • Patients usually present with recurrent renal stone disease (often require preventative management)
  • Diagnosed by USS or IVU
  • Management is usually focussed at preventing UTI and stone disease

Renovascular Disease


  • Impairment of renal perfusion caused by disease affecting the arterial supply to the kidneys
  • Typically affects white male patients, >50 with coexistent vascular disease elsewhere.
    • up to 30% of patients high-risk for vascular disease, up to 20% in patients with T2DM; up to 50% in males >70 years old (incidence increases with age)

Risk factors/Aetiology


  • Narrowing of the renal artery typically occurs due to atherosclerosis.  Significant reduction of renal flow occurs when there is >70% narrowing.
    • This causes reduced renal perfusion and thus the release of renin (and activation of the renin-angiotensin-aldosterone system (RAAS))
    • This causes a rise in blood pressure, hypokalaemia and hyponatraemia
    • Secondary hypertension can cause further progression of the atherosclerotic process and thus further narrowing of the renal artery.
    • This can eventually cause shrinkage of the kidney and renal ischaemia
  • Occasionally, particularly in younger, healthy, female patients, fibromuscular dysplasia is a more likely cause.
    • Characterised by hypertrophy of the vessel media which narrows the artery (rarely occludes)
  • Most patients do not develop kidney impairment.


  • Hypertension
    • Often severe, semi-acute onset, refractory
    • When treated with an ACEI or ARB, there is often evidence of a deterioration in renal function and patients with bilateral disease may even go into Acute renal failure
  • May also present with features of chronic kidney disease
    • e.g. proteinuria, (flash pulmonary oedema is an uncommon diagnostic feature)
  • There may be evidence of other arterial disease e.g. peripheral artery disease, coronary heart disease etc
  • Abdominal (and other) bruits may be heard on auscultation
Features/pointers to diagnosis of RAD: Young, hypertensive patients with no family history (fibromuscular dysplasia)
Peripheral vascular disease
Resistant Hypertension
Deterioration in blood pressure control in compliant, long-standing hypertensive patients
Deterioration in renal function with ACEIs
Renal impairment with minimal proteinuria
Flash pulmonary oedema
>1.5cm difference in kidney size on USS
Secondary hyperaldosteronism (low sodium and potassium)


  • Bloods
    • Renal function- U&Es; eGFR
    • Blood glucose
    • Lipids
  • Urine
    • Urinalysis
    • Urinary protein-creatinine ratio
  • Renal USS and Duplex renal ultrasound is recommended by European guidelines.  However, contrast CT angiography is often much more accurate (although is not suitable for patients with kidney failure)


  • Control risk factors
    • manage blood pressure (CCBs, ARBs and ACEIs are good BUT
      • introduce ACEIs with caution as they can reduce glomerular hydrostatic blood pressure and induce kidney failure
      • Contraindicated in bilateral (or unilateral with a single functional kidney) disease
    • statin
    • smoking cessation
    • aspirin
  • Revascularisation procedures (balloon angioplasty- endovascular)
    • Particularly in patients with refractory hypertension, flash pulmonary oedema, malignant hypertension, acute heart failure etc
    • Patients should have >60% occlusion
    • NB No good evidence to suggest this improves renal function or blood pressure, and the procedure does carry risk of renal artery occlusion, infarction and atheroemboli.
  • NB For patients with fibromuscular dysplasia, revascularisation is more beneficial and should be considered more readily


There are various definitions:

Oliguria can generally be defined as <0.5ml/kg/hour or <300ml per day (whether catheterised or not).

Anuria <50ml/day.  Anuria is an emergency requiring rapid management.


  • Urine volume is a difference of the amount of fluid filtered by the glomerulus and that reabsorbed by the renal tubules
    • It is not (directly) a measure of renal function (reduced GFR and reduced tubule reabsorption -> normal urine volume)
    • HOWEVER, it is commonly used as a physical measure of renal function in the acute setting, as reduced urine output is often one of the first physiological signs of hypovolaemia and/or shock
  • Can be a result of reduced urine production
    • Acute kidney injury e.g. pre-renal AKI in diabetic ketoacidosis, dehydration or blood loss; or intra-renal AKI e.g. in glomerulonephritis
  • Rarely a result of obstruction
    • Obstruction would have to be complete and below the level of the bladder neck; or bilateral; or unilateral on the side of a single-functioning kidney

Clinical Assessment

  • Commonly, as a doctor you will be asked to review a patient with poor urine output as a sign of patient deterioration (whether this is associated with other physiological changes e.g. heart rate/BP etc or not)
    • ABCDE!
  • THEN a History (if patient is able to give one)
    • Try and determine the timeline (onset; Any history of fluid loss e.g. diarrhoea, vomiting, bleeding, post operative)
    • Ask about PMHx and RHx
      • Stones, kidney problems in the past
      • Drugs e.g. Gentamicin, NSAIDs, ACEIs/ARBs, Antibiotics (and STOP these if renal function/U&Es are deteriorating also)
      • Diarrhoea (particularly E coli O157)
  • Look for signs of hypotension, tachycardia, tachypnoea, fever (any suggestion of sepsis/shock) and fluid depletion 
  • Palpate for bladder distension/tenderness
  • In patients with a catheter, check catheter patency before further investigations, particularly if the patient is normotensive


  • Urinalysis
    • Prerenal causes can have normal urinalysis
    • In intrinsic (AKI cause by ATN)
      • Haematuria/Proteinuria
      • There may be red cell or granular casts
  • FBC and U&Es (particularly sodium, potassium, urea, creatinine (and eGFR)
  • If infection is suspected
    • FBC, CRP
  • ABGs (metabolic acidosis)
  • Kidney USS can be performed
  • Urinary electrolytes can also be measured although this is not routine


  • Any cause of acute kidney injury
    • Prerenal
      • e.g. volume depletion (bleeding, dehydration)
      • e.g. low cardiac output (MI, heart failure, PE)
      • e.g. decreased vascular resistance (shock, sepsis)
    • Renal e.g. acute tubular necrosis, glomerular disease
    • Post-renal e.g. blocked catheter; stone disease, BPH, sphincter dysfunction (anticholinergics, post operative)

Notes on management

  • Treat reversible causes
    • Restore intravascular volume if necessary
  • Monitor fluid balance closely
    • Do not prescribe any potassium as there is a risk of hyperkalaemia
  • Dialysis may be used in patients where
    • Volume expansion that cannot be managed with diuretics
    • Refractory hyperkalaemia
    • Severe uraemia
      • NB No absolute indications- based on clinical judgement (duration, severity etc)

Membranous Nephropathy/Glomerulonephritis


  • Most common cause of nephrotic syndrome in adults (20-30%)
  • It can be primary (idiopathic) or secondary (usually due to other disease processes e.g. in SLE
  • It is often quoted that


  • Associated diseases/conditions include: SLE; Rheumatoid arthritis; drugs (gold- rarely used now; penicillamine; captopril); malignancy (commonly bronchus, colon, stomach, prostate, breast); Hep B; thyroid disease/diabetes mellitus (other autoimmune causes)
  • Cause unknown in idiopathic disease


  • Thought to be caused by an autoimmune reaction (type III- immunoglobulin deposition)
    • Antibodies involved are thought to be ‘M-type phospholipse A2 receptor’ (that is, in idiopathic disease)
    • Disease is characterised by diffuse thickening of the glomerular basement membrane with subepithelial ‘spikes’ on histology.  On fluoroscopy, this can be shown to be due to IgG and complement deposition


  • Nephrotic syndrome (75%)
    • Some patients will have proteinuria only; haematuria is rare; around 1/3 of patients will be hypertensive at Dx.


  • See nephrotic syndrome- definitive diagnosis is with a renal biopsy


  • Depends on symptoms/risk of progression to CKD
  • At presentation
    • If there is normal renal function (eGFR, creatinine etc) and <4g/day of proteinuria
      • Treat with ACE inhibitor +/- ARB to maintain BP <125/75mmHg and monitor the patient regularly
    • If proteinuria is (or increases to) 4-8g/day for more than 12 months
      • Cyclosporin +/- low dose steroid for at least 6 months (consider longer depending on response
  • Other treatments include cyclophosphamide and corticosteroids, rituximab and MMF.

Focal Segmental Glomerulosclerosis

Background and Epidemiology

  • Accounts for about 5-10% of nephrotic syndrome in children and about 40% in adults
  • Rare (estimated incidence of 7 per 1000000)
  • However, it is the most common primary glomerular disorder which causes end-stage renal failure.
  • Essentially progressive glomerular scarring

Aetiology and Types of FSGS

  • Secondary
    • I.e. to a pathological process e.g. sickle cell anaemia; HIV/Hep B infection; parvovirus B19 infection; inherited mutations of podocyte-related genes; immune-complex nephritis e.g. in SLE; drugs e.g. IV heroin, pamidronate, lithium; structural abnormalities
  • Primary (idiopathic) – most common, accounting for ~80% of cases


  • Segmental areas of glomerular sclerosis with hyalinisation of glomerular capillaries and the segmental areas usually adherent to the Bowman’s capsule
    • Focal areas of tubular atrophy and interstitial nephritis are common
  • There may be ‘collapsing’ glomerulopathy (collapsed capillaries with basement membrane wrinkling and crowding of the epithelial cells)
    • Usually worse disease and prognosis

Clinical Presentation


  • As nephrotic syndrome
    • NB Renal biopsy may appear normal depending on whether the biopsy is involved


  • High dose steroids (60-80mg/day) can be trialed.
    • About half of patients show minimal/no response after 16 weeks
  • Cyclosporine may also be tried, but rarely cause complete remission if the patient showed no response to steroid therapy
  • Patients who do not respond to therapy, and those who have severe proteinuria at presentation, are more likely to deteriorate to end-stage kidney failure
    • Patients can also recur after transplantation

Minimal Change Disease


  • MCNS is responsible for about 90% of cases of nephrotic syndrome in children under 5, and for ~20% of cases in adulthood.
    • In children, because the large majority of patients with nephrotic sydrome have MCNS- this is assumed to be the diagnosis until proven otherwise (in adults, renal biopsy is required)
  • Named because the only abnormality which can be detected is fusion/deformity of the foot process (podocytes) under the electron microscope (both light microscopy and immunofluorescence appear relatively normal)


  • Unknown aetiology- presumed to be immune-mediated (thought to be T-cell (Th2) lymphocyte involvement)
  • On electron microscopy, there is effacement of the epithelial cell foot processes over the outer surface of the glomerular basement membrane

Clinical Features/Investigations

  • Nephrotic syndrome– investigate as appropriate
  • In children, there may be a severe hypoalbuminaemia (<10g/l not uncommon)
  • Haematuria and hypertension (nephritic sydrome) are rare, as is renal failure/acute kidney injury, however they can occur
  • Children, in particular, are prone to infections e.g. cellulitis and pneumococcal peritonitis


  • Corticosteroids are usually first line (prednisolone 60mg/day (or 1g/kg/day) for 6 weeks)
    • Immunosuppressive agents (e.g. ciclosporin) can be used in patients who do not respond or who frequently relapse
    • Long-term immunomodulation (with steroids or immunosuppression) can be used in frequent relapsers.

Nephrotic Syndrome


  • Classic presentation of kidney disease, although it is rare compared to reduced kidney function (eGFR), microalbuminaemia or electrolyte disturbances
  • It occurs in about 3 in 100,000 per year in adults

Clinical Features/Definition (criteria)

Proteinuria >3g/24 hours or a single urine protein:creatinine ratio of >300mg/mmol.

Serum albumin <25 or <30g/l (depending on definition).

Clinical evidence of peripheral oedema

Severe hyperlipidaemia (total cholesterol often >10mmol/l) can also be present.


  • Increased glomerular permeability to large molecules (e.g. albumin).
    • This can be congenital i.e. disorder of the genes encoding parts of the glomerular filtration barrier (consisting of a fenestrated epithelium, basement membrane and glomerular epithelium (podocytes))
    • This may also be acquired as a result of damage to the filtration barrier (commonly autoimmune but can also be vascular)
  • Loss of protein reduces the oncotic pressure within the vasculature which, in combination with high capillary hydrostatic pressures, leads to oedema
  • Other complications include increased susceptibility to infection, hyperlipidaemia, atherosclerosis, hypocalcaemia (true or false low due to low albumin and vit D), hypercoagulability (caused by a loss of coagulation proteins e.g. antithrombin III, protein C and S, with subsequent rise in fibrinogen); hypovolaemia.

Clinical Presentation

  • Ask about any other systemic symptoms, significant past medical history/past family history, drug history (including over the counter medication), any recent acute/chronic infections or diagnoses of cancer
  • Oedema is the most common feature
    • In children, this may first be seen around the face and eyes
    • In adults, this is usually first seen around the ankles
  • Patients may also feel tired, short of breath, weakness, poor appetite (weight gain is more common than loss due to oedema); abdominal pain; may have a thromboembolic event e.g. DVT, MI; may have recurrent infections
  • Other features include frothy urine


  1. Urinalysis- confirm proteinuria (2+ or greater); also check for haematuria (1+ or greater)
    1. Exclude urine infection (MSSU for microscopy, culture and sensitivity)
  2. Measure proteinuria with early morning protein:creatinine ratio (or albumin:creatinine ratio)
    • NB 24 hour urinary protein is rarely performed in practice
  3. Blood tests
    1. FBC and Coagulation, U&Es including creatinine and renal function (eGFR), LFTs, CRP and PV, glucose
    2. Calcium/bone profile
    3. Immunoglobulins, serum and urine electrophoresis
    4. Autoimmune screen if appropriate
  4. Imaging
    1. CXR (look for effusion)
    2. Abdo/renal ultrasound
  5. Biopsy
  • Remember to investigate thromboembolic risk as appropriate e.g. lipids, Doppler USS of legs, CTPA


  • Oedema
    • NB Go slow
    • Sodium/Fluid restriction (<100mmol or 3g/day and <1.5l/day)
    • Diuretics
      • Loop diuretics e.g. furosemide first line (usually high dose IV)
        • +thiazide or potassium sparing diuretics second line
        • +albumin if patient is still not responding
  • Proteinuria
    • ACE inhibitors +/- angiotensin II receptor blocker

Causes of nephrotic syndrome

  • Primary glomerular disease
    • Minimal change nephropathy
    • Focal glomerulosclerosis
    • Membranous nephropathy
    • Membranoproliferative glomerular disease
    • Mesangiocapillary glomerulonephritis
  • Secondary glomerular disease
    • Diseases
      • Diabetes mellitus
      • SLE
      • Amyloidosis
      • Cancer (in particular myeloma and lymphoma)
      • Infections
        • e.g. HIV, Hep B and C, Mycoplasma, Syphilis, Malaria, Schistosomiasis, Toxoplasmosis
    • Drugs
      • Gold, Antibiotics, NSAIDs, penicillamine, captopril, tamoxifen, lithium
    • Congenital causes
      • Alport’s syndrome
      • Congenital nephrotic syndrome (Finnish type)
      • Pierson’s, Nail-patella, Denys-Drash syndromes
    • Other
      • Pregnancy- pre-eclampsia