Topic Discussion: Common Nephrotoxic drugs and their mode of enteries

Common Renal toxic drugs and their mode of entering the tubule and mechanism of toxicity

Drug Name	Mode of entry	Mechanism	Clinical Presentation(s)
Tenofivir(TDF)	Secreted via the basolateral side via OAT and then enters lumen via MRP2 in the urine.	Mitochondrial dysfunction	ATI Proximal tubulopathy Diabetes Insipidus(rare)
Gentamicin(Aminoglycosides)	They are all filtered and they are attracted to negative phospholipids and bind to megalin cubulin receptor and enter the cell.	Lysosomes binding and then cause mitochondrial damage and tubular injury—myelin bodies	ATI Bartter’s syndrome( via activating of the CaSR in the TAHL) Fanconi syndrome(rare)
Polymixin	All filtered, punch holes enter cells via organic cationic transporter(OCT) on apical surface	Apoptosis and necrosis	ATI
Vancomycin	Unclear how it enters	Complement activation Activation of reactive oxygen species Mitochondrial injury Vancomycin cast formations	ATI Worse when combined with Piperacillin / Tazobactam
Amphotericin B	Unclear how it enters	Principal cell defect via holes in the apical membrane	Distal hypokalemic RTA ATI Hypomagnesemia Nephrogenic DI
Heta-Starch, Dextran, Sucrose, Mannitol	Filtered and enter proximal cell – pinocytosis and build up and swell up cells. Cannot be metabolized	Osmotic nephrosis	ATI
Atazanavir	Minimal renal excretion, poorly soluble in urinary ph- leading to crystallization	Crystal formation	Crystal Nephropathy
Cisplatin	Enters via OCT on the basolateral side, enters and activates apoptosis	Oxidative stress	ATI Hypomagnesemia Proximal tubulopathy Salt wasting nephropathy Nephrogenic DI
Ifosfamide	Enters proximal tubular cell via OCT on the basolateral side and then metabolized to its metabolized that causes the damage	Increased oxidative stress and mitochondrial injury	ATI Fanconi syndrome