• Paracetamol• Acetaminophen

• N-acetyl – p-aminophenolAPAP

• Proximal tubuar necrosis + BUN ↑+• plasma Creatinine ↑• GFR & Clearance of para-aminohi ppurate ↓• Fractioned excretion of water,sodi um,potassium ↑

• Urinary glucose,protein,brush border enzyme ↑• Renal cytochrome P450APAP activa tion & nephrotoxicity• Glutathione conjugates of APAP nephrotoxicity

Amphotericin B

• ADH – resistant polyuria• Renal tubular acidosis• Hypokalemia• ARF or CRF

The functional integrity of Glomerulus,Proximal and distal portions of the nephron is impaired RBF ↓ & GFR ↓ secondary to renal arteriolar vasoconstriction oractivation of tubuloglomerular feedback

AminoglycosidesNonoliguric renal failure with :• GFR ↓• Serum creatinine ↑• BUN ↑• PolyuriaThe earliest lesion: increase in the size &number of lysosomes,which contain phospholipid caused by inhibition ofLysosomal hydrolases

(sphingomyelinase & phospholipase)

CyclosporineManifestation:• Acute reversible renal dysfunction• Acute vasculopathy• Chronic nephropathy + interstitial fibro sis

Acute reversible renal dysfunction (doserelated).Cyclosporine vasoconstriction:RBF↓ , GFR↓ ,BUN↑ ,serum Creatinine↑

Acute vasculopathy or thrombotic microangiopathy affects arterioles and glomerular capillaries. Hyaline and/or fibroid changes,often

with fibrinogen deposisition (in arterio le) . Thrombosis with endothelial cell

desquamation affects glomerular capil laries. Long-term treatment can result in chro nic nephropathy with interstitial

fibrosis

Cisplatin

Cisplatin nephrotoxicity includes:• Acute renal failure• Chronic renal failure• Renal magnesium wasting• Polyuria

ARF is characterized by:RBF ↓ ,GFR ↓ ,Enzymuria , β2-microglobulinuria,inappropriate losses of

magnesium.

• CRF is due to prolonged exposer and is characterized by :focal necrosis in numerous segment of the nephron without a significant effect on the

glomerulus. Cisplatin may produce nephrotoxicity through its ability to inhibit DNA synthe sis as well as transport functions.

Nonsteroidal Anti-inflammatory Drugs(NSAID)

ARF may occur within 3 hours after a large dose of NSAID ,ussually reversi

ble upon withdrawal of yhe drug (acute).• RBF↓ ,GFR↓ , OliguriaNSAIDs inhibit PGI2 (vasodilatory PG)Vasoconstriction (by CA & A II) RBF↓and ischaemia.

• Chronic consumption of NSAIDs and/or APAP (>3 years)irreversible nephrotoxicity i.e. papillary necrosis with chronic interstitial nephritis. The mechanism of nephropayhy = ? -chronic medullary/papillary ischaemia secondary to renal vasoconstriction -genesis of a reactive intermediate that in turn initiates an oxidative stress or binds covalently to critical cellular macromolecules.

• Albeit rare,NSAIDsInterstitial nephri tis: serum creatinine & proteinuria. If NSAIDs are discontinued,renal func- tion improves in 1 to 3 months.

Radiocontrast Agents

Iodinated contrast media potentiallyNephrotoxic in patients with existing re-nal impairment,Diabetes,Heart failure,who are receiving other nephrotoxicdrugs.

The newer nonionic contrast (iotrol,iopa-midol) have lower toxicity.