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NEPHROTIC CAUSES OF
ACUTE KIDNEY FAILURE
Nephrotoxic causes of acute kidney
failure
Endogenous nephrotoxins
Myoglobin
Myoglobinuric acute
kidney
failure, the mechanism of which remains uncertain, is typically
associated with crush injury to muscle, but there are a large
number of causes of non-traumatic rhabdomyolysis. A high index
of suspicion is required to diagnose cases that are not
obviously associated with muscle injury, since muscular pain,
swelling, and tenderness may not be prominent features and can
even be absent.
The key to making the diagnosis is to detect myoglobin in the
urine, or a very high level of enzymes released from muscle in
the plasma. The former is recognized by the combination of
dark-brown ('coca cola') urine that tests positive for 'blood'
on a reagent strip, but which does not contain red cells on
microscopy. The muscle enzyme usually measured in plasma is
creatine kinase: the normal range of this is up to just below
200 U/l; in rhabdomyolysis values above 10 000 U/l are commonly
seen, a value of only 1–2000 U/l not being enough to establish
the diagnosis of rhabdomyolytic acute
kidney
failure in the absence of other supporting evidence. Extremely
high levels of plasma myoglobin, aldolase, and lactic
dehydrogenase are also seen, all being released from damaged
muscle.
Rhabdomyolysis can be associated with very high plasma levels of
urate (>750 µmol/l), phosphate (>2.5 mmol/l), aspartate and
alanine transaminase (AST in the many hundreds of U/l,
exceptionally in the thousands; ALT in the few hundreds of U/l;
respectively), and with an unusually low plasma calcium
concentration (<1.5 mmol/l). Any of these findings should lead
to serious consideration of rhabdomyolysis in any patient with
unexplained acute
kidney
failure.
If
the diagnosis of rhabdomyolysis is made, then the question of
whether to initiate an alkaline diuresis arises, since on
theoretical grounds it would be anticipated that alkalinization
of the urine would lead to enhanced excretion of the putative
toxin and protect against acute
kidney
failure. Victims of crush injury have been treated with infusion
of very large volumes of fluid (12 litres/day) and high doses of
mannitol (160 g/day) and bicarbonate (240 mmol/day). In
comparison with historical (almost certainly volume-depleted)
controls the incidence of
kidney
failure has been impressively reduced, but the difficulties of
controlling potassium balance in the face of such a massive
diuresis should not be underestimated. It may well be that
avoidance of hypovolaemia using a less aggressive and more
easily managed fluid regimen would be equally efficacious.
Haemoglobin
In
several situations, acute
kidney
failure is seen in association with massive haemolysis: malaria,
glucose-6-phosphate dehydrogenase deficiency, mismatched blood
transfusion, arsine poisoning, copper sulphate poisoning, burns,
and as a complication of bladder irrigation with hypotonic
solutions. In each circumstance it is possible, but not proven,
that the development of acute renal failure might be
attributable to, or exacerbated by, the presence of large
amounts of free haemoglobin within the circulation.
Urate
The
tumour lysis syndrome is associated with a rapid rise in plasma
uric acid concentration (and almost certainly liberation of
other nephrotoxins) as a complication of the treatment of
lymphoma, leukaemia, myeloma, or other 'high-turnover' tumours.
This can result in the deposition of urate crystals in the
distal tubule, which can both cause physical obstruction and
initiate an inflammatory response, leading to acute
kidney
failure in which freshly voided urine is heavily laden with
urate crystals. Hyperuricaemia and
kidney
failure have been described on rare occasions after recurrent
epileptic seizures.
Hyperuricaemic acute
kidney
failure is predictable and hence potentially avoidable in the
context of the treatment of malignancy. The most important issue
is that dehydration should be avoided at all costs, and a brisk
saline diuresis should be initiated at least 24 h before the
initiation of chemotherapy if possible. The use of an alkaline
diuresis has been advocated, since uric acid is undoubtedly more
soluble in alkaline urine, but this may encourage the
precipitation of phosphate within the renal tubules and should
not be employed if the serum phosphate is high. It is common
practice in many centres to give allopurinol, even at a dosage
above the usual 300 mg/day, but others would not do so on the
grounds that this may encourage xanthine nephrotoxicity,
although the risks of this seem to have been overstated.
If
hyperuricaemic acute
kidney
failure does develop, then it is unlikely that any of the
treatments described above, or diuretics, will reverse the
condition. Prompt improvement usually follows reduction of the
plasma uric acid concentration, which is best accomplished by
haemodialysis. On very rare occasions the ureters can become
obstructed by urate crystals—indicated by colic, pelvicalyceal
distension, or persistent oliguria—and ureteral catheterization
and washout may be required.
Other endogenous nephrotoxins
More uncommon even than intratubular obstruction by urate
crystals is similar obstruction by phosphate, also seen in the
context of massive cell destruction in the treatment of
malignant disease. Urinary alkalinization should be avoided
because it may promote intratubular phosphate precipitation.
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