Renal 3

Question 1

Tubulointerstitial nephritis - acute

Answer 1

Inflammation of the renal interstitium - mediated by an immune reaction to medications (e.g. NSAIDs, penicillin’s, rifampicin, furosemide, thiazides, allopurinol or amphotericin), infections (e.g. Staph, Strep, Brucella, Leptospira) or immune disorders (e.g. glomerulonephritis) or it may have no known cause.

• Features – may present with renal impairment, hypertension or acute renal failure with systemic features – fever, rash, arthralgia plus eosinophilia, uveitis and high IgE levels.
• Diagnosis – renal biopsy shows infiltration of the renal interstitium and tubules with T cells, macrophages and plasma cells and urinary eosinophil’s may also be found.
• Management – stop the cause and give 1mg/kg Prednisolone – most will fully recover.

Question 2

Tubulointerstitial nephritis - chronic

Answer 2

Results from many disorders leading to extensive fibrosis and tubular loss on renal biopsy and presents with chronic renal failure. Causes include chronic pyelonephritis often with reflux nephropathy, sickle cell disease or lead or cadmium intoxication.

Question 3

Balkan nephropathy

Answer 3

A form of CIN (chronic interstitial nephritis) causing progression to end stage renal failure. It is endemic in areas along the river Danube with both environmental and genetic factors thought to be important.

Question 4

Analgesic nephropathy - definition and signs

Answer 4

Associated with prolonged, heavy ingestion of compound analgesics (especially those containing caffeine (as it leads to habituation), NSAIDs and paracetamol) leading to interstitial nephritis and papillary necrosis. There is often a past medical history of chronic pain.

• * Signs* – slowly progressive chronic renal failure - in advanced disease there’s anaemia, hypertension and >3.5g/day proteinuria is common. Renal colic and haematuria can also occur.

Question 5

Analgesic nephropathy - investigations and management

Answer 5

• Investigations – CT without contrast as it’s the most sensitive test and a renal biopsy which will show CIN (IVU is not as sensitive as a CT scan and in some cases can be nephrotoxic).
• Management – stop analgesics! Sudden flank pain should prompt an ultrasound or IVU to look for obstruction from a sloughed papilla. There is also an increased risk of urothelial tumours.

Question 6

Acute urate nephropathy

Answer 6

Acute oliguric or anuric renal failure due to uric acid precipitation within the tubules.

It is most often due to overproduction of uric acid in patients with lymphoma, leukaemia or a myeloproliferative disorder – particularly after chemotherapy has induced rapid cell lysis. Plasma urate is raised and there are bifringent crystals on microscopy.

Management - keep well hydrated, give allopurinol before chemotherapy and alkalinise urine with sodium bicarbonate (uric acid more soluble).

Question 7

Chronic urate nephropathy

Answer 7

Whether chronic hyperuricaemia (e.g. with gout) leads to renal failure is debated, however this does occur in Lesch-Nyhan syndrome. Management is with allopurinol.

Question 8

Hypercalcaemia

Answer 8

Associated with the following renal diseases – nephrogenic diabetes insipidus, renal caliculi and nephrocalcinosis – diffuse renal parenchymal calcification which is often asymptomatic but causes progressive renal impairment. Investigations - perform an abdominal x-ray for caliculi or nephrocalcinosis.

Question 9

Radiation nephritis

Answer 9

Renal impairment following radiotherapy and can be acute (<1 year) or chronic. It causes hypertension, proteinuria and leads to chronic renal failure. Renal biopsy will show interstitial fibrosis. Management – strict BP control but it needs to be prevented with adequate shielding.

Question 10

Exogenous nephrotoxins

Answer 10

Analgesics (NSAIDs), antibiotics (gentamicin, sulphonamides, tetracycline, vancomycin, amphotericin or acyclovir), radio-contrast media, anaesthetic agents, chemotherapeutic agents, ACEi and ARBs, immunosuppressants, heavy metal poisoning, organic solvents or insecticides.

Question 11

Endogenous nephrotoxins

Answer 11

Pigments (e.g. haemoglobinuria in haemolysis or myoglobin in rhabdomyolysis), crystals (e.g. urate) or proteins (e.g. light chain immunoglobulins in myeloma).

Question 12

Nephrotoxins - aminoglycosides

Answer 12

Gentamicin, amikacin and streptomycin – well recognised nephrotoxins. They typically cause mild non-oliguric renal failure 1-2 weeks into treatment. Risk is increased by old age, renal hypoperfusion, pre-existing renal impairment, high dosage or prolonged treatment and co-administration of other nephrotoxins. A single bolus dose of aminoglycosides is less nephrotoxic.

Question 13

Nephrotoxins - radiocontrast nephropathy

Answer 13

A very common cause of iatrogenic acute renal failure. Risk factors are diabetes, high doses of contrast medium, hypovolaemia, other nephrotoxic agents and pre-existing renal impairment. Prevention is key – stop nephrotoxic agents peri-procedure and pre-hydrate patients with risk factors with IV 0.9% sodium chloride.

Question 14

Rhabdomyolysis - definition

Answer 14

Results from skeletal muscle breakdown with release of its contents into the circulation – myoglobin, K+, PO43-, urate and creatine kinase. Complications include hyperkalaemia and acute renal failure – myoglobin is filtered by the glomeruli and precipitates, obstructing renal tubules.

Question 15

Rhabdomyolysis - causes

Answer 15

Post ischaemia (embolism or clamp on artery during surgery), trauma (prolonged immobilisation e.g. after falling, burns, crush injury, excessive exercise or uncontrolled seizures), drugs and toxins (statins, fibrates, alcohol, ecstasy, heroin, snake bite, carbon monoxide or neuroleptic malignant syndrome), infections (Coxsackie, Epstein Barr virus or influenza), metabolic (hypokalaemia, hypophosphataemia, myositis or malignant hyperpyrexia) or inherited muscle disorder (McArdle’s disease or Duchenne muscular dystrophy).

Question 16

Rhabdomyolysis - clinical features

Answer 16

Features of the cause plus muscle pain, swelling and tenderness and red brown urine.

Question 17

Rhabdomyolysis - investigations

Answer 17

Plasma CK >1000 iU/L (exclude MI as cause) and urinary myoglobin. Potassium, phosphate and urate will be raised and serum calcium will be low (moves into muscles).

Question 18

Rhabdomyolysis - management

Answer 18

Urgent treatment of hyperkalaemia, IV rehydration to prevent acute renal failure – maintain urine output >300mL per hour until myoglobinuria has ceased. IV sodium bicarbonate can also be used to alkalinise the urine to pH >6.5 to stabalise the less toxic form of myoglobin. Dialysis may be needed in severe cases but a full renal recovery usually occurs.

Question 19

Renal vascular disease - hypertension

Answer 19

May be a cause or consequence of renal disease.

• Essential hypertension – whether moderate hypertension causes renal disease is debated.
• Accelerated (aka malignant) hypertension – is characterised by a rapid and severe increase in blood pressure, grade 3 or 4 hypertensive retinopathy and renal failure.
• Renal diseases causing hypertension – the commonest causes of 2° hypertension – diabetic nephropathy, glomerulonephritis, chronic interstitial nephritis, PKD or renovascular disease.

Question 20

Reno-vascular disease - causes

Answer 20

Stenosis of the renal artery or one of its branches –

causes – atherosclerosis (in 80% - in over 50s, arteriopaths, co-existent IHD, stroke and peripheral vascular disease) or fibromuscular dysplasia (in 10% - in younger women).

Rarer causes include – Takayasu’s arteritis, antiphospholipid syndrome, post-renal transplant, thromboembolism or external mass compression.

Question 21

Reno-vascular disease - presentation

Answer 21

Hypertension that is resistant to treatment, worsening renal function after giving ACEi or ARB in bilateral artery stenosis, flash pulmonary oedema, sudden onset left ventricular impairment, abdominal, carotid and femoral bruits and weak leg pulses may be found.

Question 22

Reno-vascular disease - investigations and management

Answer 22

• Investigations – renal ultrasound for kidney size (affected side is smaller) with Doppler for renal artery flow disturbance. CT/MRI is more sensitive to measure renal artery blood flow and should be performed before angiography (gold standard) as they are less invasive.
• Management – transluminal angioplasty ± stent insertion or surgical revascularisation.

Question 23

Haemolytic uraemic syndrome

Answer 23

Characterised by microangiopathic haemolytic anaemia (MAHA) – intravascular haemolysis and red cell fragmentation due to narrowing or obstruction of small vessels.

Mechanism – endothelial damage triggers thrombosis, platelet consumption and fibrin strand deposition mainly in the renal microvasculature. These strands cause mechanical destruction of passing red blood cells. Thrombocytopenia and acute renal failure are the results.

Question 24

HUS - causes and signs

Answer 24

• Causes – 90% are caused by E Coli strain O157 - this produces a verotoxin which damages endothelial cells. It typically affects children in outbreaks after eating undercooked meat.
• Signs – abdominal pain, bloody diarrhoea and acute renal failure.

Question 25

HUS - investigations and management

Answer 25

• Investigations – the blood film shows fragmented red blood cells (schistocytes), low platelets, anaemia but clotting tests are normal. In addition there may be proteinuria and haemoaturia.
• Management – often resolves spontaneously but dialysis for renal failure may be required.

Question 26

Thrombotic thrombocytopenic purpura - definition

Answer 26

A sextet of symptoms including fever, fluctuating CNS signs (e.g. seizures, hemiparesis, decrease in consciousness), microangiopathic haemolytic anaemia (MAHA), low platelets (causing mucosal bleeding), renal failure and proteinuria or haematuria.

Question 27

TTP - mechanism and causes

Answer 27

• Mechanism – there is a genetic or acquired deficiency of a protease that normally cleaves von Willibrand factor. Large vWF multimers form causing platelet aggregation and fibrin deposition in small vessels, leading to microthrombi. It affects adults and mortality is higher than HUS.
• Causes – often unknown but can be drugs (clopidogrel, ciclosporin), pregnancy, HIV or SLE.

Question 28

TTP - investigations and management

Answer 28

• Investigations – the presence of anaemia and thrombocytopenia should raise suspicion.
• Management – a haematological emergency get expert help – plasma exchange is life-saving. Steroids, IV vincristine, IV immunoglobulin or splenectomy may be required in resistant cases.