Acute tubular necrosis is a
common and important cause of reversible acute renal failure
In acute tubular necrosis (ATN),
metabolic or toxic disturbances cause necrosis of renal tubular epithelial
Although the tubular epithelial cells die and are shed, regeneration is possible
if the damaging stimulus is corrected, since residual viable tubular epithelial
cells can proliferate to re-populate the tubules.
It is this regenerative capacity of the tubular epithelial cells that permits
adequate tubular functioning after renal transplantation following a prolonged
period of hypoxia of the graft.
There are three phases to ATN:
1 Oliguric phase. A damaging
stimulus causes necrosis of renal tubular epithelium. There is blockage of renal
tubules by necrotic cells, and a secondary reduction in glomerular blood flow
(caused by arteriolar constriction) reduces glomerular filtration.
Macroscopically, kidneys are diffusely swollen and oedematous. Patients develop
acute renal failure and oliguria. Supportive measures are required to prevent
hyperkalaemia and fluid overload.
2 Polyuric phase. Over 1-3
weeks, regeneration of renal tubular epithelium takes place, with removal of
dead material by phagocytic cells, as well as in the form of casts in urine. As
tubules open up and glomerular blood flow increases, patients develop polyuria.
This is because the regenerated tubular cells are undifferentiated and have not
developed the specializations necessary for resorption of electrolytes and
water. Replacement of fluid and electrolytes is needed to compensate for
excessive loss from urine.
3 Recovery phase. Tubular
cells re-establish differentiation and there is restoration of renal function.
Rare functional disturbances
Metabolic abnormalities may
cause secondary tubular damage
Urate nephropathy is seen in a
small proportion of patients with hyperuricaemia. Precipitation of urate
crystals occurs in the renal collecting ducts, causing tubular damage,
inflammation and later scarring.
Other crystal nephropathies
are rare, the most important being associated with the inherited matabolic
disorder, primary hyperoxaluria, in which oxalate crystals are precipitated in
tubules and lead to extensive tubular and interstitial damage. This eventually
leads to chronic renal failure.
Nephrocalcinosis is caused by
persistent hypercalcaemia. Calcification occurs in the renal parenchyma,
particularly tubular basement membrane, with tubular damage and later fibrosis.
During development of this condition there is failure of tubular function, with
development of polyuria.
Myeloma causes casts of
secreted Bence-Jones protein to precipitate out in renal tubules, causing
physical obstruction of tubules. Amyloid may develop in glomeruli (see amyloid)
and, if the myeloma is associated with hypercalcaemia from bone destruction,
there may be superimposed nephrocalcinosis. Urography with certain contrast
agents may precipitate acute tubular blockage and acute renal failure.