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NEPHROTIC CAUSES OF
ACUTE KIDNEY FAILURE
Specific causes of acute kidney failure
▪
Prerenal
failure and acute tubular necrosis
▪
Vascular causes of acute
kidney
failure
▪
Nephrotoxic causes of acute
kidney
failure
▪
Glomerulonephritic and vasculitic causes
of
acute kidney failure
▪
Interstitial nephritis as a cause of acute
kidney
failure
▪
'Haematological' causes of acute
kidney
failure
▪
Hepatokidney Syndrome
▪
Tropical
Nephrotoxic causes of acute kidney
failure
Exogenous nephrotoxins
A
wide variety of exogenous agents, including therapeutically
prescribed drugs, can cause acute
kidney
failure. The following are worthy of particular note.
Aminoglycosides
Gentamicin, amikacin, kanamycin, and streptomycin are all
potentially nephrotoxic, as are tobramycin and netilmicin to a
lesser degree. These drugs are usually prescribed for patients
thought to be suffering from potentially fatal infections, hence
in clinical practice it is frequently impossible to separate
with certainty the harmful effects of aminoglycosides from those
of the underlying condition, or of other drugs used in
treatment.
However, evidence from animal models supports the view that
these agents are genuinely nephrotoxic, rather than that their
prescription is simply a marker for severe infection, which is
itself a potent cause of acute
kidney
failure.
The
risk of nephrotoxicity is increased by old age, pre-existing
renal insufficiency, high dosage, prolonged treatment, combined
treatment with other nephrotoxic drugs, renal ischaemia, and
volume depletion. It has been stated that acute
kidney
failure complicates up to 25 per cent of therapeutic courses of
gentamicin, even when monitoring optimally controls drug levels.
Parenteral administration is not required for the development of
toxicity: acute
kidney
failure can occur as a result of systemic absorption when
aminoglycosides are used in irrigating or bowel-sterilizing
solutions. The typical clinical picture is of relatively mild
non-oliguric
kidney
failure coming on 1 to 2 weeks after starting treatment. Tubular
proteinuria and impaired ability to concentrate the urine
precede a loss of glomerular filtration rate. Proximal tubular
damage involves the brush border, reflected by increased urinary
excretion of g-glutamyl transferase, alanine aminopeptidase, and
of lysosomal enzymes. Recovery may be slow, delayed, or
incomplete.
The
nephrotoxicity of particular aminoglycosides is related to the
strength of their positive charge. They bind to negatively
charged membrane phospholipids, particularly in the kidney to
parts S1 and S2 of the proximal tubule, where they are delivered
to megalin (the Heymann nephritis autoantigen, a member of the
low-density lipoprotein (LDL) receptor family) in coated pits.
The complex is endocytosed and trafficked to the endosome, where
gentamicin inhibits fusion in vivo and in vitro. Polyaspartic
acid polymers normalize fusion and ameliorate nephrotoxicity,
suggesting that binding of other ligands to megalin may be
useful in limiting aminoglycoside uptake and nephrotoxicity, but
this possibility has not yet been explored clinically.
Aminoglycosides should only be used in the relatively uncommon
circumstance that there is no suitable alternative antibiotic
that is not nephrotoxic, and careful monitoring of levels is
mandatory to avoid toxicity if gentamicin or similar agents must
be used.
Radiographic contrast media
The incidence of acute
kidney
failure associated with the use of radiographic contrast media
has been reported to vary between 0 and 50 per cent. This
extraordinary variability reflects differences in other risk
factors in the populations under examination and in the
definition of
kidney
failure used. Recent prospective studies, using non-ionic
contrast media and in which careful attention has been paid to
the maintenance of adequate hydration, have shown a very low
incidence of significant
kidney
impairment—even in groups reported to be at high risk (diabetes,
myeloma). When
kidney
impairment does occur it is usually mild.
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