Last updated on May 25, 2019 at 21:04
Acute tubular nephropathy, or acute tubular necrosis (ATN) as it’s been known as in the last 40 years, is responsible for 80% of all renal parenchymal causes of acute renal failure. It’s mortal in 5- 10% of cases, where permanent damage is sustained, but in the majority of cases will the kidney functions be normalized.
We have two types of ATN: Ischaemic type and toxic type.
Ischaemic acute tubular necrosis
Ischaemic ATN involves such a severe hypoperfusion that there will be hypoxia of the tubules. This requires a larger reduction of RBF than for prerenal acute kidney failure. Common causes include:
- Circulatory shock
- Severe stenosis of renal artery
The RBF sinks so much that the kidney shunts blood away from the glomeruli and towards the tubules. It accomplishes this by constricting the afferent and dilating the efferent vessels of the glomeruli, which reduces the filtration pressure significantly. The glomeruli also start to swell, which further decreases the permeability. These changes cause the GFR to drop significantly.
Despite the shunting toward the tubules will they suffer ischaemia. Necrotic tubular cells may obstruct the tubules.
If the causing agent is removed or resolved will the RBF and GFR return to normal quickly. However, the tubules are damaged and need a lot of time to recover. Some tubular cells sustain so much damage that their basement membrane is damaged as well, a process called tubulorrhexis. These tubular cells can’t regenerate.
Toxic acute tubular necrosis
Common involved toxins include:
- X-ray contrast material
- Heavy metals
Common for all these substances is that they are secreted by the proximal tubules, which undergo necrosis. The damage doesn’t affect tubules diffusely but rather mostly at the proximal part. Tubulorrhexis may occur.
GFR is originally normal, but Na+ reabsorption in the tubules is deficient, so more Na+ will reach the macula densa, which will then decrease the GFR by tuberu-glomerular feedback (TGF).
ATN follows three phases. These phases are followed even if the RPF recovers early.
- The initiation phase
- The maintenance phase
- The recovery phase
The initiation phase occurs in the first days and is defined by very low GFR. The hypoperfusion is most pronounced in the inner cortex and outer medulla. Ischaemic tubular cells lose their microvilli, and they relocate their Na+/K+ ATPase pumps from the basal side to the apical side (that faces the filtrate). Parenchymal degeneration of the tubules occurs.
The damaged tubules can’t perform active transport, but loss of tight junctions causes back-leak of filtrate back into the peritubular capillaries and interstitium.
Necrotic cell debris blocks the tubules, further decreasing the filtration in a similar way to postrenal ARF.
The maintenance phase lasts for weeks. The GFR remains low at around 5 – 10 mL/min even though the RBF is normalized. At this point is the uraemia so severe that symptoms of it occur.
Low GFR persists due to these factors:
- Damaged endothelial cells produce more vasoconstrictors and less vasodilators
- Tubero-glomerular feedback causes afferent vessel constriction in order to try and reduce the GFR (the macula densa believes the GFR is high because more Na+ reaches it)
When damaged cells are reperfused will reperfusion damage occur because of free radicals, causing further damage to the kidney.
The recovery phase can take months and involves regeneration of those tubular cells that did not lose their basement membrane. The GFR slowly increases. As necrotic debris is cleared from the lumen may polyuria occur. Hyposthenuria remains while the tubular cells aren’t working properly.
Dialysis must be regularly performed while in the recovery phase.
- Increased thirst
- High anion-gap metabolic acidosis
Hyposthenuria occurs because of impaired active transport, especially in the loop of Henle. The urine will contain necrotic cell debris. The resulting salt and water retention cause generalized oedema, wet lung and possibly pulmonary oedema. For some reason is thirst enhanced. If the patient drinks more water may hypoosmolar hypervolaemia with hyponatraemia occur.
Hyperkalaemia occurs due to low GFR.
The kidneys can’t excrete all the acid produced by the metabolism, so a metabolic acidosis with high anion-gap will occur (we’ll get to what that is later). This enhances K+ loss from cells, worsening the hyperkalaemia.
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