Acute tubular necrosis

Classification

ATN may be classified as either toxic or ischemic. Toxic ATN occurs when the tubular cells are exposed to a toxic substance (nephrotoxic ATN). Ischemic ATN occurs when the tubular cells do not get enough oxygen, a condition that they are highly sensitive and susceptible to, due to their very high metabolism. Due to several reasons, the proximal portion of the renal tubule is most commonly injured in ATN.

Diagnosis

Acute tubular necrosis is classified as a "renal" (i.e. not pre-renal or post-renal) cause of acute kidney injury. Diagnosis is made by a FENa (fractional excretion of sodium) 3% and presence of muddy casts (a type of granular cast) in urinalysis. On histopathology, there is usually tubulorrhexis, that is, localized necrosis of the epithelial lining in renal tubules, with focal rupture or loss of basement membrane. Proximal tubule cells can shed with variable viability and not be purely "necrotic".

Toxic ATN

Toxic ATN can be caused by free hemoglobin or myoglobin, by medication including antibiotics such as aminoglycoside,{{cite journal |last1=Tulkens |first1=P.M. |date=March 1989 |title=Nephrotoxicity of aminoglycoside antibiotics |url=https://dx.doi.org/10.1016/0378-4274%2889%2990121-5 |journal=Toxicology Letters |volume=46 |issue=1–3 |pages=107–123

Histopathology: Toxic ATN is characterized by proximal tubular epithelium necrosis (no nuclei, intense eosinophilic homogeneous cytoplasm, but preserved shape) due to a toxic substance (poisons, organic solvents, drugs, heavy metals). Necrotic cells fall into the tubule lumen, obturating it, and determining acute kidney failure. Basement membrane is intact, so the tubular epithelium regeneration is possible. Glomeruli are not affected.

Ischemic ATN

Ischemic ATN can be caused when the kidneys are not sufficiently perfused for a long period of time (i.e. renal artery stenosis) or during shock. Hypoperfusion can also be caused by embolism of the renal arteries. Given their importance in massive nutrient and electrolyte reabsorption, the proximal tubule and medullary thick ascending limb require significant ATP and are most susceptible to ischemic damage. Thus, ischemic ATN specifically causes skip lesions through the tubules.

Ischemic ATN often involves reperfusion injury to the kidney. When oxygen flow is restored, damage can occur due to oxygen radicals, inflammatory cells and molecules and tissue edema. These processes can exacerbate injury and worsen the prognosis. Nevertheless, restoring blood flow is essential for tissue survival, so clinical strategies aim to minimize the harmful effects.

References

References

1. Desanti De Oliveira, B., Xu, K., Shen, T.H. et al. Molecular nephrology: types of acute tubular injury. Nat Rev Nephrol 15, 599–612 (2019). https://doi.org/10.1038/s41581-019-0184-x
2. (2008). "Acute Tubular Necrosis (ATN)". HealthCommunities.com.
3. Goldman, Lee. (2008). "Cecil medicine". Saunders Elsevier.
4. Goldman, Lee. (September 2010). "Cecil medicine". Saunders Elsevier.
5. [http://medical-dictionary.thefreedictionary.com/tubulorrhexis TheFreeDictionary > tubulorrhexis] Citing: The American Heritage Medical Dictionary 2007
6. (November 2001). "Coexpressed nitric oxide synthase and apical beta(1) integrins influence tubule cell adhesion after cytokine-induced injury". Journal of the American Society of Nephrology.
7. (June 1999). "Inflammatory cytokines induce apoptotic and necrotic cell shedding from human proximal tubular epithelial cell monolayers". Kidney International.
8. Racusen LC. (1998). "Epithelial cell shedding in acute renal injury". Clinical and Experimental Pharmacology & Physiology.
9. (May 1993). "Morphology of ischemic acute kidney injury, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients". Kidney International.
10. (April 1991). "Dissociation of tubular cell detachment and tubular cell death in clinical and experimental 'acute tubular necrosis'". Laboratory Investigation.
11. (May 2003). "Short-Term, High-Dose Pamidronate-Induced Acute Tubular Necrosis: The Postulated Mechanisms of Bisphosphonate Nephrotoxicity". American Journal of Kidney Diseases.
12. (2008-07-01). "The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury". Molecular Medicine Reports.