From the Guidelines
Acute Tubular Necrosis (ATN) is primarily caused by ischemia, nephrotoxicity, and sepsis, with nephrotoxicity being a major contributor, particularly from medications such as cisplatin, ifosfamide, and gemcitabine, as well as from targeted cancer agents and cancer immunotherapies, as highlighted in the most recent study 1. The causes of ATN can be broken down into several key categories:
- Ischemic ATN, which occurs due to reduced blood flow to the kidneys, often resulting from severe hypotension, major surgery, trauma, hemorrhage, or heart failure.
- Nephrotoxic ATN, which develops from exposure to substances harmful to kidney tubules, including:
- Medications such as aminoglycosides, amphotericin B, cisplatin, and contrast media.
- Targeted cancer agents, such as anti-angiogenesis drugs, B-Raf and anaplastic lymphoma kinase inhibitors, and proteasome inhibitors.
- Cancer immunotherapies, including immune checkpoint inhibitors.
- Heavy metals, organic solvents, and myoglobin from rhabdomyolysis.
- Sepsis-induced ATN, which happens when systemic infection triggers inflammatory responses that damage kidney tubules. Other contributing factors include:
- Prolonged urinary obstruction
- Severe burns
- Certain autoimmune conditions The pathophysiology of ATN involves direct tubular cell injury, leading to cell death, tubular obstruction from cellular debris, and backleak of filtrate across damaged tubular epithelium, as discussed in 1 and 1. Prevention of ATN focuses on maintaining adequate renal perfusion, careful dosing of nephrotoxic medications, proper hydration before contrast procedures, and prompt treatment of sepsis and rhabdomyolysis to minimize kidney damage, as emphasized in 1.
From the Research
Causes of Acute Tubular Necrosis (ATN)
The causes of ATN can be divided into several categories, including:
- Nephrotoxic causes: resulting from exposure to toxic substances, such as certain medications, heavy metals, or organic solvents 2, 3, 4
- Ischemic causes: resulting from reduced blood flow to the kidneys, which can be caused by conditions such as cardiogenic shock, hypotension, or sepsis 2, 3, 5
- Mixed causes: a combination of nephrotoxic and ischemic causes 2, 3
Types of ATN
There are several types of ATN, including:
- Pure nephrotoxic ATN: caused by toxic substances, with a relatively better prognosis 2, 3
- Pure ischemic ATN: caused by reduced blood flow, with a relatively poorer prognosis 2, 3
- Mixed ATN: a combination of nephrotoxic and ischemic causes, with a variable prognosis 2, 3
Clinical Outcomes
The clinical outcomes of ATN can vary depending on the cause and type of ATN, with:
- Nephrotoxic ATN having a relatively better prognosis, with lower mortality rates and higher dialysis-free survival rates 2, 3
- Ischemic ATN having a relatively poorer prognosis, with higher mortality rates and lower dialysis-free survival rates 2, 3
- Mixed ATN having a variable prognosis, depending on the underlying causes and comorbidities 2, 3