Aminoglycoside antibiotics can cause acute kidney injury (AKI) in 10-15% of patients through nephrotoxic mechanisms. Risk factors include pre-existing kidney dysfunction, hypokalemia, and reduced effective arterial volume. AKI occurs 5-7 days after treatment and is usually non-oliguric and mild, though it can be severe. Prevention focuses on selecting less toxic aminoglycosides, correcting electrolyte abnormalities, limiting duration of therapy, and minimizing other nephrotoxins. While various compounds have shown promise in preventing aminoglycoside-induced nephrotoxicity, none are used clinically.

1. Aminoglycoside induced
Nephrotoxicity

2. Aminoglycoside induced
Nephrotoxicity
• Introduction
• Risk factors
• Mechanism of Nephrotoxicity
• Clinical implications for prevention
• Conclusion

3. Introduction
• AKI – relatively common complication of aminoglycosides
• Incidence- 10 to 15%
• Cationic structure plays an important role in the toxicity
In spite of undesirable side effects AGs are still used because of
their
• Chemical stability
• Fast bactericidal effect,
• Synergy with beta lactams
• Little resistance
• Low cost

4. Risk factors

5. Mechanism of AG induced nephrotoxicity

6. Mechanism of AG induced Nehrotoxicity

7. Glomerular effects of AG induced
nephrotoxicity

8. Vascular effects of AG induced nehrotoxicity

9. Clinical features
Non oliguric AKI
• AKI due to AGs occur 5 to 7 days after treatment
• Non-oliguric AKI due to loss of concentrating ability
due to distal tubular damage
• ATN due to AG unlikely to be severe , usually mild
• It can cause severe AKI requiring HD in patients with
CKD

10. Clinical features
Distal tubular dysfunction
• Polyuria- because of loss of concentrating capacity
• Hypomagnesemia – because of increased losses
Electrolyte abnormalities
• Hypomagnesemia, Hypokalemia, Hypocalcemia,
Hypophosphatemia
• Fanconi like syndrome- glycosuria, aminoaciduria,
phosphaturia, uricosuria

11. Clinical course
• Plasma creatinine resolves within 21 days after
cessation of the drug
• However resolution of acute episode may be delayed in
septic, hypovolemic and catabolic conditions
• Irreversible kidney damage- uncommon in acute AG
induced nephrotoxicity
• However it can occur in prolonged therapy, even in low
doses

12. Evolution of AKI in AG Induced Nehrotoxicity

13. Role of inflammation

14. Prevention
• Selection of least toxic AGs
• Correcting hypokalemia and hypomagnesemia prior to
AG
• Avoiding AG in patients with reduced effective arterial
volume or optimizing volume status prior to
administration of AG
• Adjusting dose for renal function
• Limiting duration of therapy
• Minimize concomitant nephrotoxic medications
• Using once daily regimen

15. Agents tried to prevent AG induced
nephrotoxicity
• PAAs(Polyaminoacids)
Polyaspartic acid and Polyglutamic acid
• Other compounds
Antioxidants such as desferrioxamine , methimazole,
vitamin C and E , Selenium
Superoxide , lipoic acid, DMSO,NAC and melatonin also
has utility in AG induced nephrotoxicity prevention

16. Conclusion
• There are many factors that determine the nephrotoxicity
due to AGs
• Its very important for clinicians to know all the factors
contributing so as to reduce AG induced nephrotoxicity
• Although pattern of AKI in AG induced nephrotoxicity
occurs 5 to 7 days after AG exposure, it can be difficult to
differentiate from other causes, as it occurs in the setting
of significant comorbid conditions , sepsis and
nephrotoxin exposure

17. • Hence essential step in diagnosis of AG induced
nephrotoxicity is attention to other potentially reversible
etiologies
• In addition review of all imaging procedures for contrast
exposure and concomitant nephrotoxin use is imperative
• Though many agents have emerged as potential
compounds to prevent AG induced nephrotoxicity, none
has been adopted clinically