Iatrogenic Hospital Acquired Acute Kidney Injury: A wider scope for better outcomes Dr. K. Hoe MBBS DipMedSc DM (Int Med) FACP FUWI (Clinical Nephro) Consultant Nephrologist, UWI (Mona)

Where is the origin of fire at the fire station? Avoid nephrotoxic agents Avoid NSAIDs & Aminoglycosides

Which is more important to set fire, lighter or fuel? Exposures Susceptibilities Sepsis Dehydration or volume depletion Critical illness Advanced age Circulatory shock Female gender Burns Black race Trauma CKD Cardiac surgery Chronic diseases (heart, lung, liver) Major noncardiac surgery Diabetes mellitus Nephrotoxic drugs Cancer Radiocontrast agents Anemia Poisonous plants and animals CKD, chronic kidney disease; CPB, cardiopulmonary bypass 2012 KDIGO guidelines for AKI

Kk hoe et al; e-published. DOI 7727/wimj.2018.154

Anything missing? Exposures Susceptibilities Sepsis Dehydration or volume depletion Critical illness Advanced age Circulatory shock Female gender Burns Black race Trauma CKD Cardiac surgery Chronic diseases (heart, lung, liver) Major noncardiac surgery Diabetes mellitus Nephrotoxic drugs Cancer Radiocontrast agents Anemia Poisonous plants and animals CKD, chronic kidney disease; CPB, cardiopulmonary bypass 2012 KDIGO guidelines for AKI

Factors Associated with Drug-Induced Nephrotoxicity Drugs Exposure Patient

Drug factors for nephrotoxicity Abs (Pen, S’mide) NSAIDs, PPI, Aminoglycoside aminoglycosides platinums, amphotericin B and colistin positive charge of polycationic aminoglycosides methotrexate, acyclovir, indinavir/atazanavir, sulfadiazine, vitamin C, foscarnet, oral sodium-phosphate, and triamterene adefovir, cidofovir, tenofovir disturb mitochondrial function dextran, hydroxyethyl starch accumulate within phagolysosomes  interaction of uromodulin with vancomycin

strategic handling of AKI

Patient factor Comorbid Diseases Patients with HIV receiving tenofovir who developed Fanconi syndrome were noted to have a single nucleotide polymorphism Comorbid Diseases

Gender distribution of HA-AKI cases and its severity at UHWI

kk hoe et al unpublished data

Factors Associated with Drug-Induced Nephrotoxicity Drugs Exposure Patient

Drug‐Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database Most AKI reports were generated for medications not recognized as nephrotoxin Hanna K et al ACCP jnl: August 2018; 38 (8):785-793 Total # of AKI (n=193996) Prevalence of exposure Known nephrotoxin 16.5% New potential nephrotoxin 64.8% Possible nephrotoxin 18.6%

Drug ROR 95% CI Aprotinin 115.7 110.63, 121.01 Sodium phosphate 55.81 51.78, 60.17 Frusemide 12.61 11.94, 13.32 Vancomycin 12.19 11.45, 12.99 Metformin 10.65 10.31, 11.00

Kk hoe et al on going trial 2016-18

Wider scope is necessary to prevent Iatrogenic HA-AKI Drugs Exposure Patient

Conclusion Know