History and exam

Key diagnostic factors

common

oliguria or anuria

Oliguria and anuria, although not diagnostic, may be present in ATN. Oliguria is usually present in the maintenance phase. Nephrotoxic ATN is less prone to show oliguria than ischemic ATN due to fluid depletion.

hypotension

Common in ATN due to fluid depletion.

tachycardia

Common in ATN due to fluid depletion.

Other diagnostic factors

common

poor oral intake and anorexia

Patients may have poor oral intake, and anorexia.

malaise

Patients may have malaise.

uncommon

thirst

Excessive fluid loss (as a result of hemorrhage, burns, gastrointestinal losses, or sweating) may present with symptoms of hypovolemia, including thirst.

dizziness

Excessive fluid loss (as a result of hemorrhage, burns, gastrointestinal losses, or sweating) may present with symptoms of hypovolemia, including dizziness.

orthopnea/dyspnea

May occur if advanced cardiac failure is present leading to reduced renal perfusion.

edema

Patients with fluid loss, sepsis, or pancreatitis may have signs of circulatory collapse including edema.

Risk factors

strong

chronic kidney disease (CKD)

Pre-existing CKD increases susceptibility to acute kidney injury (AKI). Lower levels of glomerular filtration rate are associated with higher risk of AKI.[13]

chronic hypertension

Patients with chronic hypertension are more vulnerable to situations of hypoperfusion as the kidney’s autoregulation processes are impaired. Due to chronic structural changes in renal arterioles and small arteries, afferent arteriolar resistance does not decrease as it should, or may even increase in situations of hypoperfusion, increasing the susceptibility of renal ischemia.[2]

diabetes mellitus

Multiple studies have shown that diabetes is an independent risk factor for acute kidney injury.[14][15][16] Incidence rates of acute kidney injury of 9% to 38% have been reported in cases of patients with diabetes and chronic kidney disease undergoing contrast exposure.[17]

advanced age

Advanced age is associated with a higher prevalence of chronic kidney disease, underlying renal vascular disease, and other comorbid medical conditions that predispose to ATN.[18]

low-perfusion states

Hypotension and/or excessive fluid loss from hemorrhage, the gastrointestinal tract (e.g., vomiting and diarrhea), sweating, or burns may cause a decrease in renal blood supply, which can lead to ischemic injury and result in ATN. Anasarca (severe and generalized edema), such as may occur in congestive heart failure or cirrhosis, may cause reduced kidney perfusion. Cardiac arrest or mechanical ventilation can lead to alterations of hemodynamics and worsen renal function.

The sensitivity of individual patients to a decrease in renal perfusion is variable. For example, some patients suffer from ATN after a few minutes of hypoperfusion, while others tolerate several hours of ischemia without structural damage to the kidney. In fact, several studies have shown how acute kidney injury may develop with normal or even increased renal perfusion due to a dysfunction of the intrarenal microcirculation, which appears to play an important role in the pathogenesis.[19][20] It is not clear whether this is a direct cause of kidney injury as a result of inflammatory diseases such as sepsis, or an adaptive mechanism.[20]

sepsis

Sepsis is the most common condition associated with acute kidney injury (AKI) in hospital and intensive care units (ICUs).[1] Globally, it has been reported in almost 50% of patients with severe AKI in ICUs. In Europe, AKI has been reported in up to 51% of patients with sepsis, with a mortality up to 41% in ICUs. Sepsis is characterized by a systemic inflammatory response to an infection. The pathogenesis of septic AKI is still not fully understood. Systemic vasodilation leads to a decrease in renal blood supply and resulting ischemia. There is also direct toxic injury generating an inflammatory response, with vascular injury (endothelial dysfunction, microvascular obstruction, vasoconstriction, coagulopathy, and vascular edema) as well as tubular injury.[1]

major surgery

Certain types of surgery are associated with higher risks of renal hypoperfusion, such as in vascular surgery, where the aorta is cross-clamped above the renal arteries. Cold ischemia can occur during renal transplantation, renal surgery, or renal artery thrombosis and can lead to ischemic injury and ATN. The pathophysiology of acute kidney injury following cardiac surgery is complex and involves multiple factors (including pre-, intra-, and post-operative factors). Hypoperfusion, ischemia-reperfusion injury, neurohormonal activation, oxidative stress, and inflammation leads to vasoconstriction that leads to a reduction in renal perfusion and renal ischemia.[20]

exposure to nephrotoxic agents

Examples include nonsteroidal anti-inflammatory drugs, amphotericin-B, aminoglycosides, chemotherapeutic agents (e.g., cisplatin), calcineurin inhibitors (tacrolimus, cyclosporine), and poisons (e.g., ethylene glycol). ATN occurs in 10% to 20% of patients receiving aminoglycosides.[5]

exposure to radiocontrast media

Exposure to radioisotopic contrast media may cause ATN within 7 days after exposure.[3][5][21] Incidence is variable and influenced by patient-related factors, such as pre-existing chronic kidney disease and diabetic nephropathy. The type and volume of contrast (>350 mL), as well as repeated administration within 72 hours can also increase the risk.[21]

exposure to endogenous toxins

Muscle trauma (e.g., crush injury) may cause rhabdomyolysis, which will produce an increased myoglobin release that can occlude the renal filtration. Hemolysis, increased hemoglobin release, can lead to ATN. In patients with multiple myeloma there may be increased light chain proteins precipitated into the tubular lumen associated with myeloma of the kidney. Bacterial toxins may also cause toxic injury and result in ATN. Hyperuricemia (e.g., gout, tumor lysis syndrome) leads to acute crystal-induced nephropathy, which may result in ATN.

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