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Drug-Induced Acute Kidney Injury (DIAKI) can be classified in type A reactions, in which the mechanism of aggression is explained by the drug pharmacology (time of use and dose) and in type B reactions, when the nephrotoxicity can not be predictable and depends on drug pharmacogenetics and corresponds to Acute Interstitial Nephritis (AIN), crystalline nephropathy and tubular diseases (Bartter-like or Gitelman-like). This study aimed to determine the incidence of DIAKI, the associated drugs, its phenotypes and the main prognostic factors.
Retrospective cohort study that included AKI patients evaluated by the Nephrology team from Brazil from 2016 to 2022. Patients <18 years or undergoing chronic dialysis were excluded. Variables analyzed were age, gender, AKI etiology, drug involved and phenotype of nephrotoxicity, KDIGO classification, need for Acute Kidney Support Therapy (AKST), use of vasoactive drugs (VAD), need for mechanical ventilation (MV), outcome (death or not) and acute tubular necrosis – index specific score (ATN-ISS).
We studied 1401 AKI patients.The most prevalente etiology was mixed AKI (ischemic + septic) (28%), ischemic AKI (19.4%), mixed DIAKI+others (14.4%), septic AKI (10%)] and DIAKI (4.9%). Age was 64.03±14.46 years, severe AKI (KDIGO 3) was more common (44.5%), followed by Chronic Kidney Disease(CKD)+AKI (37.8%), 42.8% patients were admitted at ICU, ATN-ISS score was 0.50±0.28 and mortality was 33.6%. DIAKI were 20.1% of all AKI cases. Patients that had DIAKI were younger, less severe and had lower mortality than patients that had other AKI etiologies. Table 1 shows a comparison between all AKI and DIAKI patients.
The most DIAKI type was type A reactions (75.8%) and 20.3% were type B, being 14.6% AIN, 3.2% Bartter-like tubulopathies and 2.5% cristalline nephropathies.
The most prevalent drugs related to type A reactions were Vancomycin (41.3%), contrast agentes (36.2%), Amphotericin B (7%) and aminoglycosides (3%). The most prevalent drugs that caused AIN were Polymyxin B (29.3%), non-steroidal anti-inflammatory (21.9%) quinolones (17%) and cephalosporions (12.2%). Crystalline nephropathy was related to Aciclovir, and Bartter-like to Polymyxin B.
Among patients with DIAKI, factors associated with need for AKST were ATN-ISS scores, ICU hospitalization, VAD, MV and mixed etiology of AKI (DI+others), as shown in table 2. Risk factors for mortality were similar, except mixed etiology of AKI. The nephrotoxic drugs were also associated with the need for AKST (p<0.001, with higher risk for Vancomicin and lower risk for contrast agents and Amphotericin B), but there was not association with mortality (p=0.65). Type A reactions were associated with more need for KST (p<0.001), but not with higher mortality (p=0.47).
Conclusions
DIAKI was an importante cause of AKI (20.1%), presenting lower severity and mortality when compared to other AKI etiologies, however, with similar need for AKST. Most of the nephrotoxic drugs were type A reactions, which were associated with higher need for AKST, but not with higher mortality. The main nephrotoxin was Vancomycin, suggesting that DIAKI can be a preventable cause of AKI, decreasing expenditures to the health system and improving outcome.