Acute Kidney Injury: ATN and AIN

Pathophysiology

The American Journal of Transplantation and Hepatology recommend that ATN primarily affects the tubular epithelial cells due to ischemia or toxins, while AIN involves inflammation of the renal interstitium typically caused by immune-mediated reactions, most commonly to medications 1, 2
ATN is characterized by damage to the tubular structures with necrosis of tubular epithelial cells, according to Hepatology 2
ATN may present with acid-base or electrolyte disturbances even without changes in kidney function, as reported by Annals of Oncology 3
ATN accounts for approximately 29% of renal biopsies in patients with acute kidney injury, according to Annals of Oncology 3
AIN is characterized by inflammation within the kidney interstitium, most commonly caused by medications, as stated by Kidney International 4
AIN represents 80-90% of immune-related renal dysfunction in patients on immunotherapy, according to Annals of Oncology 3, 5

Nephrotoxic causes of ATN include antibiotics, contrast media, and chemotherapeutic agents, as reported by Kidney International 6, 7
Drug-induced AIN is the most common cause, with antibiotics, NSAIDs, and proton pump inhibitors being common culprits, according to Kidney International 4
Immune checkpoint inhibitors can cause AIN, as stated by Kidney International 6

Clinical context often suggests diagnosis of ATN, particularly in patients with recent hypotension or nephrotoxin exposure, as reported by Hepatology 2
Definitive diagnosis of AIN requires kidney biopsy showing interstitial inflammation, according to Annals of Oncology 5, 8

The primary intervention for AIN is discontinuation of the offending agent, as recommended by Annals of Oncology 5, 8
Corticosteroids are often used to treat AIN, especially drug-induced cases, according to Annals of Oncology 5, 8
For immune checkpoint inhibitor-related AIN, high-dose methylprednisolone (1 mg/kg) is recommended, as stated by Annals of Oncology 3, 5
Supportive care with focus on fluid management is the primary treatment approach for ATN, as reported by Hepatology 2
Removal of nephrotoxic agents is crucial in the treatment of ATN, according to Journal of Hepatology 9

The American Gastroenterological Association recommends using fractional excretion of sodium (FENa) and fractional excretion of urea (FEUrea) to differentiate prerenal causes from structural causes like ATN, with limited specificity in cirrhosis 10
Biomarkers like NGAL (neutrophil gelatinase-associated lipocalin) can help differentiate ATN from AIN and other causes of AKI, with NGAL levels in ATN significantly higher than in AIN or prerenal azotemia, and a cutoff value of 220-244 μg/g of creatinine suggested for differentiation 10

NGAL levels can be used to differentiate ATN from AIN, with a significant difference in levels between the two conditions, and a recommended cutoff value for differentiation 10

The American College of Physicians recommends using urinary NGAL as a biomarker to differentiate ATN from AIN, with a cutoff of 220-244 μg/g creatinine, and notes that multiple elevated tubular injury biomarkers increase the likelihood of ATN 11
The use of fractional excretion studies, such as FENa and FEUrea, has limited value in differentiating ATN from AIN, with FENa having poor specificity and FEUrea being more reliable in patients receiving diuretics 11
The European Renal Association suggests that these measures are unreliable for distinguishing ATN from AIN specifically, and that urinary NGAL measured 2 days after presentation performs better than serum NGAL 11, 12

The American Diabetes Association notes that diabetic patients are more vulnerable to complications from acute pyelonephritis and may not present with typical flank tenderness 13