From the Guidelines
Acute Tubular Necrosis (ATN) is primarily caused by nephrotoxicity from substances such as cytotoxic chemotherapeutic drugs, targeted cancer agents, and cancer immunotherapies, as well as ischemia and sepsis. The causes of ATN can be multifactorial, including:
- Nephrotoxicity from cytotoxic chemotherapeutic drugs, such as platinum-containing compounds (especially cisplatin), ifosfamide, gemcitabine, methotrexate, and pemetrexed 1
- Targeted cancer agents, which can cause new or worsened hypertension, proteinuria, and lesions such as thrombotic microangiopathy (TMA), minimal change disease/focal segmental glomerulosclerosis, and acute interstitial nephritis (AIN) 1
- Cancer immunotherapies, which can cause AKI and proteinuria (sometimes nephrotic), primarily due to AIN, but also ATI 1
- Ischemia, which can occur due to reduced blood flow to the kidneys, as seen in severe hypotension, shock, major surgery, trauma, or severe dehydration
- Sepsis, which can cause ATN through a combination of inflammatory mediators, microvascular dysfunction, and direct cellular injury
Other contributing factors include:
- Rhabdomyolysis, where myoglobin damages tubules
- Hemolysis, where free hemoglobin causes tubular injury
- Pre-existing kidney disease, diabetes, advanced age, or volume depletion, which can increase the risk of ATN
The pathophysiology of ATN involves direct cellular damage to the tubular epithelium, leading to cell death, tubular obstruction from cellular debris, and backleak of filtrate across damaged tubular walls. Prevention strategies include maintaining adequate hydration, avoiding nephrotoxic drug combinations, appropriate dosing of medications in patients with reduced kidney function, and prompt treatment of conditions that may lead to kidney hypoperfusion 1.
From the Research
Causes of Acute Tubular Necrosis (ATN)
The causes of ATN can be divided into several categories, including:
- Ischemic causes: resulting from reduced blood flow to the kidneys 2, 3, 4
- Nephrotoxic causes: resulting from exposure to toxic substances, such as certain drugs 2, 3, 5
- Mixed causes: resulting from a combination of ischemic and nephrotoxic factors 2, 3
Mechanisms of ATN
The mechanisms of ATN involve:
- Proximal tubular injury and acute tubular necrosis (ATN) due to apical contact with drugs or their metabolites 5
- Tubular obstruction by crystals or casts containing drugs and their metabolites 5
- Interstitial nephritis induced by drugs and their metabolites 5
Clinical Context
ATN is often observed in the context of:
Prognosis and Treatment
The prognosis of ATN is often severe, and despite functional recovery, the cellular repair is abnormal, leading to accelerated renal aging and increased susceptibility to nephrotoxicity 6. Currently, there is no specific treatment for ATN, but regular monitoring of renal function and simple nephroprotection measures are recommended 6.