Drug-Induced Kidney Disease Unit 2

Risk factors for drug-induced kidney disease

• Advanced age > 70

• Male gender 

• African American

• Pre-existing renal disease 

• Diabetes 

• Heart failure 

• Nephrotoxic drugs 

• Sepsis 

• Volume depletion 

• Cirrhosis surgery 

• Shock 

• Acidosis 

NSAID Nephropathy…

Mechanism

• Ischemic kidney damage 

• Decreased synthesis of renal vasodilator 

• Reduced renal perfusion and pressure

Risk Factors for NSAID Nephropathy 

• Age > 60 

• Pre-existing kidney disease 

• Hepatic disease 

• CHF

• Volume depletion lupus 

• ACEi/ARB usage

NSAID Nephropathy Prevention?

→ avoid use in high-risk patients 

• Maintain adequate hydration if decided to do so 

Treatment

• DC NSAID and other nephrotoxic meds

• Reversible recovery within 3 - 5 days 

NSAIDs Brand and Generic

1. Etodolac (Lodine)

2. Nabumetone (Relafen)

3. Sulindac (Clinoril)

Cyclosporine and Tacrolimus Nephropathy

Presentation 

Occurs within days of initiation 

• Rise in Scr

• Hypertension 

• Hyperkalemia 

• Sodium retention 

• Renal tube acidosis 

• Hypomagnesemia

Prevention of Cyclosporine and Tacrolimus Nephropathy?

→ PD/PK monitoring + decreased doses when used with other immunosuppresants

→ TREATMENT: 

• Acute injury: dose reduction or discontinuation of interacting meds

• Chronic injury: NOT dose related and IRREVESIBLE 

SGLT-2 Inhibitor Nepropathy…

Canagliflozin and dapagliflozin AKI complication 

• Osmotic diuresis leads to VOLUME DEPLETION 

• Sodium chloride delivery vasoconstricts and REDUCES GFR

RISK FACORS?

• Older age 

• ACEi, ARB, NSAID, Diuretic concomitant use 

• Volume depletion

TX?

• DC SGLT2i

• IV fluids for volume depletion 

Aminoglycoside Nephrotoxicity Ranking?

1. Neomycin (most)

2. Gentamicin

3. Tobramycin 

4. Amikacin (least)

Aminoglycoside Nephrotoxicity

Toxicity related to cationic charge of the drug…

• Select alt agents when possible

• Avoid volume depletion 

• Limit total dose

Radiographic Contrast Media-Induced Nephrotoxicity (CIN)

→ presents within first 24-48 hours after administration 

• Scr PEAKS between 3-4 days after exposure 

• Recovery 7-10 days 

Radiographic Contrast Media-Induced Nephrotoxicity (CIN) Mechanism 

• Renal ischemic (systemic hypotension and acute vasoconstriction) 

• Direct cellular toxicity 

RISK FACTORS:

• Pre-existing kidney disease 

• Decreased renal flow 

• Diabetes

• Nephrotoxins

Radiographic Contrast Media-Induced Nephrotoxicity (CIN) PREVENTION?

• Use alt. Imaging 

• Contrast: use noniodinated contrast, minimize contrast volume/dose 

Hydration?

• Isotonic saline: 1 - 1.5 mL/kg/hr to maintain urine rate of 150 mL/hr

  • 3 to 12 hours prior and continue 6 - 24 hours AFTER exposure

• URGENT: 0.9 NaCl 3 mL/kg/hr

  • 1 hour prior and 6 hours after 

Amphotericin B Nephrotoxicity Presentation

• Non-oliguria (normal urine output)

• Rise in Scr and BUN

• Renal tubular potassium, sodium, and magnesium wasting 

• Distal renal tubular acidosis 

• Tubular dysfunction 1 - 2 weeks after initiation 

Amphotericin B Nephrotoxicity MoA

• DIRECT tubular epithelial cell toxicity 

  • Necrosis of proximal tubular cells

• Afferent arterioar vasoconstritction 

  • Reduction in renal blood GFR

Amphotericin B Nephrotoxicity RISKS

• Short infusion time

• Volume depletion 

• Hypokalemia 

• large/cumulative doses 

Amphotericin B Nephrotoxicity Prevention?

• Liposomal formulation 

• Limit cumulative doses

• INCREASING INFUSION TIME 

Hydration: 

• 1 L of 0.9 NaCl IV daily during therapy 

• 10 - 15 mL/kg prior to amphotericin B

Amphotericin B Nephrotoxicity Treatment?

• DC therapy and use other antifungal

Drug-Induced Acute Interstital Nephritis 

Systemic manifestation of hypersensitivity reaction

Presents: fever, rash, arthralgia, eosinophilila

Drugs:

• Penicillin

• Cephalopsorin 

• NSAIDs

• Diuretics 

• PPI

Treatment: 

• DC offending

• IF RENAL FAILURE > 7 days, steroids 

  • High dose prednisone 1 mg/kg/day for 4-6 weeks with 4 week taper

Drug-induced Post-renal acute renal failure 

→ obstruction of urine flow from crystal formation or retroperitoneal fibrosis 

• Drugs

  • Acyclovir 

  • Sulfonamides 

  • Methotrexate 

  • High dose vitamin C

  • Indinavir, atazanavir 

Prevention/Treatment?

• Urine alkalinization