Diuretics Can Cause Acute Tubular Necrosis (ATN)

Yes, diuretics can cause acute tubular necrosis (ATN) through excessive diuresis leading to volume depletion and renal hypoperfusion. 1

Mechanisms by which diuretics can lead to ATN

Diuretic-induced excessive diuresis is a common precipitating factor of acute kidney injury (AKI) in patients with cirrhosis and heart failure 1
Excessive use of diuretics can decrease blood pressure, impair renal function, and reduce exercise tolerance 1
Volume depletion from aggressive diuresis leads to renal hypoperfusion, which can progress to acute tubular necrosis if prolonged 1
The risk is heightened when multiple diuretics are used in combination (e.g., loop diuretics with metolazone), which may cause severe electrolyte depletion and further decline in glomerular filtration rate (GFR) 1

Urinalysis may show increased urinary sodium, reduction in urine nitrogen concentration, and typical urinary sedimentation findings 1
Fractional excretion of sodium (FENa) >1% is suggestive of ATN, while FENa <1% suggests prerenal causes 1, 3
Fractional excretion of urea (FEUrea) may better discriminate between prerenal azotemia and ATN, especially in patients receiving diuretics 1, 3
Biomarkers of renal tubular injury such as neutrophil gelatinase-associated lipocalin (NGAL) can help differentiate ATN from other causes of AKI 1
A urinary NGAL cutoff value of 220-244 μg/g of creatinine has been reported as best for differentiating ATN from prerenal azotemia 1

Monitor serum creatinine and electrolytes regularly when patients are on diuretics 1
Adjust diuretic dosage based on daily weight measurements 1
Avoid combining diuretics with other nephrotoxic medications when possible 1
In patients with cirrhosis undergoing therapeutic paracentesis, administer albumin infusion to prevent renal dysfunction 1
In patients with heart failure, carefully titrate diuretic doses to avoid excessive diuresis 1
Consider intravenous administration of diuretics (including continuous infusions) in patients with diuretic resistance rather than excessive dose escalation 1

Discontinue diuretics immediately when AKI is detected 1
Provide appropriate volume replacement based on the cause and severity of fluid loss 1
In hypovolemic AKI, volume replacement should aim to reduce serum creatinine to 0.3 mg/dL of baseline level 1
In severe cases with refractory fluid retention, continuous veno-venous hemofiltration (CVVH) may be necessary 1
Combining CVVH with positive inotropic agents may increase renal blood flow, improve renal function, and restore diuretic efficiency 1

Mortality rates from ATN in hospitalized and ICU patients are approximately 37.1% and 78.6%, respectively 4
Nephrotoxic ATN generally has a better prognosis (38% mortality) compared to ischemic (66% mortality) and mixed ATN (63% mortality) 5
In patients without pre-existing chronic renal failure, recovery of renal function typically occurs without sequelae, even after an episode of ATN requiring dialysis 2
Oliguria is universally associated with increased mortality in all types of ATN 5

Hypotension and azotemia may occur as a result of either excessive diuresis or worsening heart failure; distinguishing between these causes is crucial for appropriate management 1
If there are no signs of fluid retention, hypotension and azotemia are likely related to volume depletion and may resolve after reducing diuretic dose 1
If signs of fluid retention persist with hypotension and azotemia, this likely reflects worsening heart failure and declining effective peripheral perfusion—an ominous clinical scenario requiring urgent intervention 1
Even mild-to-moderate increases in serum creatinine or decreases in GFR are independently associated with worse prognosis 1