DRUG-INDUCED NEPHROTOXICITY

• Drug-Induced Nephrotoxicity is increasingly recognized as a significant contributor to kidney disease including Acute Kidney Injury (KI) and chronic kidney disease (CKD).
• Nephrotoxicity has a wide spectrum, reflecting damage to different nephron segments based upon individual drug-mechanisms.

1. ACE-INHIBITORS:

• ACE-Inhibitors are frequently associated with Proteinuria and Renal Insufficiency.
• The prevalence of Proteinuria in Captopril treated patient is estimated to be 1%.
• The risk of Renal Insufficiency is greater with long-acting ACE Inhibitors such as Lisinopril or Enalapril than with Captopril.
• Immune complex glomerulopathy is a major contribute to ACE Inhibitor nephrotoxicity.
• Predisposing factors include:

1. Hyponatremia
2. Diuretic therapy
3. Pre-existing renal impairment
4. Congestive Heart Failure (CHF)
5. Diabetes Mellitus

• Recovery of renal function usually follows ACE-Inhibitor discontinuation.

2. CEPHLOSPORIN:

• The cephalosporin antibiotics are capable of producing rare Interstitial Nephritis similar to Penicillin's.
• Increase in BUN and Cr(s) occur occasionally.
• Nephrotoxicity of newer drugs is minimal compared with older such as Cephalothin.

3. DIURETICS(THIAZIDE):

• Occasional cases of Interstitial Nephritis have been reported, which might be the result of hypersensitivity reaction.
• Lomg-term use of diuretics increases the risk of Renal cell carcinoma, especially in women.

4. NSAIDs:

• NSAIDs including COX-2 Inhibitors can reduce Cr (Cl) and produce renal insufficiency as a result of renal circulatory changes caused by inhibition of PG synthesis. These effects are usually reversible.
• The prevalence is usually 1%.
• Predisposing factors include:

1. Old age
2. Preexisting renal impairment
3. Hypotension
4. CHF
5. Hepatic cirrhosis

• Fenoprofen is the NSAID most commonly associated with interstitial nephritis and nephrotic syndrome.

5. OMEPRAZOLE:

• Interstitial nephritis occurs rarely during omeprazole therapy.
• At least 13 cases were published; 10 with positive biopsies; 5 cases were rechallenged with recurrence of interstitial nephritis in all.
• Onset is usually after 2 weeks to 6 months of Omeprazole therapy.