Renal ischaemia - most common cause:
- haemorrhage, burns, diuretics
- myocardial infarction, congestive cardiac failure
- diarrhoea and vomiting, fluid loss from fistulae
- pancreatitis, endotoxic shock
- abruptio placentae, pre-eclampsia and eclampsia
- snake bite (-> DIC)

Direct renal toxins
- aminoglycosides, NSAIDs, ACEIs (in presence of renal arterial disease), platinum derivatives
- NSAIDs inhibit prostaglandin production - hence removing inhibition of the rapid glomerular arteriolar dilatation caused by ACEIs -> exacerbates effect
- radiological contrast agents

- hepatorenal syndrome - rapidly reversible vasomotor abnormalities in kidney
- haemoglobinaemia, myoglobiaemia - trauma, pressure necrosis, heroin abuse -> occlusion of renal tubules by haemoglobin and myoglobin casts

Mechanism - incompletely understood
- entry of Ca into cells -> increased intracellular [Ca]
- hypoxia induces NOS -> production of nitric oxide
- increased production of intracellular proteases e.g. calpain (in cyclosporin toxicity)
- activation of phopholipase A2 -> increased ffa production -> damage to cell membranes
- cell injury resulting from reperfusion
- vasoconstriction
- liberation of toxic endothelial factors
- damage from vasodilator effect of endotoxins
- reduced prostaglandin production
- tubular obstruction by desquamated cells and casts

-> patchy tubular cell necrosis with disruption of cell membrane, denaturation of intracellular protein, lysosomal disruption and cell necrosis
- tubular cells are able to regenerate quickly and re-form the basement mebrane - this explains the reversibility of ATN

Reduced glomerular filtration is due to:
- glomerular contraction
- reflex afferent arteriolar spasm
- "back-leak" of filtrate in the proximal tubule
- obstruction of the tubule by debris

Symptoms of uraemia
- anorexia, nausea, vomiting, pruritus
- intellectual clouding, drowsiness, fits, coma, haemorrhagic episodes
- epistaxes and gastrointestinal haemorrhage

History
- duration of symptoms
- previous urinalysis/renal function results

Biochemical features
- rate at which urea and creatinine rise depends on rate of tissue breakdown
- hyperkalaemia is common; especially in patients with trauma to muscle or in haemolytic states
- hyponatraemia may be present if there is fluid overload
- pulmonary oedema due to salt and water retention is common
- hypocalcaemia due to decreased renal production of 1, 25 dihydroxycholecalciferol is common
- hyperphosphataemia is common - phosphate retention

Acute or chronic uraemia?
- rapid rate of change in serum urea / creatinine suggests an acute process
- a normochomic, normocytic anaemia may suggest chronic disease; however, anaemia may be due to acute haemolysis
- USS - small kidneys of increased echogenicity are diagnostic of a chronic process
- renal osteodystrophy indicates chronic disease
- carbamylated Hb?

Prerenal, renal or postrenal?
- bladder outflow obstruction is ruled out by insertion of a catheter or flushing an existing catheter (which should then be removed unless a large amount of urine is obtained)
- absence of upper tract dilatation on USS generally rules out urinary tract obstruction
- CVP measurement can be useful in distinguishing prerenal from renal failure; if there is low volume -> fluid resuscitation; if there is no diuresis, intrinsic renal failure is present

Urinalysis
Urine microscopy and culture - dirty brown granular casts
U&Es, creatinine, PO4, albimin, alk. phos., urate
FBC and peripheral blood film
Clotting
Blood levels of nephrotoxic drugs

- aim is to keep the patient alive until spontaneous recovery occurs
- early specialist referral is advisable

General measures
- regular oral toilet and chest physiotherapy
- consistent documentation of fluid intake and output, body weight

Emergency measures

Hyperkalaemia
- risk of VF
- calcium gluconate 10 mL 10% solution iv - reduces cardiac sensitivity to hyperkalaemia
- serum [K] is reduced using an infusion of100 mL of 50% dextrose + 10u rapid-acting insulin
- correction for acidosis using iv sodium bicarbonate also reduces serum K; rapid correction of acidosis can displace Ca from albumin-binding site -> increased free Ca -> tetany
- in many patients, hyperkalaemia can only be corrected by dialysis of haemofiltration

Pulmonary oedema
- diuresis using iv frusemide
- if this fails, dialysis or haemofiltration

Sepsis
- treat infections promptly; avoid nephrotoxic drugs
- doses of drugs excreted by kidney should be adjusted; as for all drugs

Fluid and electrolyte balance
- twice daily clinical assessment - overload/hypovolaemia; weight
- daily intake should = urine output + losses from fistulae and vomiting + 500 mL (for insensible loss); additional allowance for febrile patients
- minimize sodium and potassium intake

Diet
- sodium and potassium restriction
- dietary protein is occasionally restricted; carries risk of negative nitrogen balance
- enteral intake if possible
- vitamin supplements

Dialysis and haemofiltration
- in the presence of symptoms of uraemia, complications of uraemia, severe biochemical derangement (especially rising trend in oliguric patient), uncontrolled hyperkalaemia, pulmonary oedema, severe acidosis, or for removal of drugs resposible for the acute renal failure
- options include peritoneal dialysis, intermittent hamodialysis with ultrafiltration, intermittent haemofiltration, continuous arteriovenous or venovenous haemofiltration, or haemodiafiltration
- haemofiltration has fewer adverse cardiovascular effects than haemodialysis