General Nephrotoxic Factors

The nephron

Cortex

The nephron

Cortex

t 1 Lithium ! ! Ischemia

Vulnerability of the kidney

Sites of renal damage

^ ACE inhibitors ^ NSAIDs ( ) Aminoglycosides

Acyclovir ^^^^ Cisplatinum HgCl2

t 1 Lithium ! ! Ischemia

Vulnerability of the kidney

•Important blood flow (1/4 cardiac output)

• High metabolic activity

• Largest endothelial surface by weight •Multiple enzyme systems •Transcellular transport •Concentration of substances •Protein unbinding

•High O2 consumption/delivery ratio in outer medulla

FIGURE 11-1

Sites of renal damage, including factors that contribute to the kidney's susceptibility to damage. ACE—angiotensin-converting enzyme; NSAID—nonsteroidal anti-inflammatory drugs; HgCl2—mercuric chloride.

DRUGS AND CHEMICALS ASSOCIATED WITH ACUTE RENAL FAILURE

Mechanisms

M1 Reduction in renal perfusion through alteration of intrarenal hemodynamics M4 Intratubular obstruction by precipitation of the agents or its metabolites or byproducts

M2 Direct tubular toxicity

M5 Allergic interstitial nephritis

M3 Heme pigment-induced toxicity (rhabdomyolysis)

M6 Hemolytic-uremic syndrome

M1 M2

M3

M4

M5*

M6

Drugs

ZZ

Z

Cyclosporine, tacrolimus

ZZ

Amphotericin B, radiocontrast agents

Z

Z

Nonsteroidal anti-inflammatory drugs

Z

Angiotensin-converting enzyme inhibitors, interleukin-2^

ZZ

Z

Methotrexate^

Z

Aminoglycosides, cisplatin, foscarnet, heavy metals, intravenous immunoglobulin^, organic solvents, pentamidine

Z

Z

Cocaine

Z

Ethanol, lovastatin**

Z

Z

Sulfonamides

Z

Acyclovir, Indinavir, chemotherapeutic agents, ethylene glycol***

Z

Allopurinol, cephalosporins, cimetidine, ciprofloxacin, furosemide, penicillins, phenytoin, rifampin, thiazide diuretics

Z

Conjugated estrogens, mitomycin, quinine

* Many other drugs in addition to the ones listed can cause renal failure by this mechanism. t Interleukin-2 produces a capillary leak syndrome with volume contractions. § Uric acid crystals form as a result of tumor lysis. ^ The mechanism of this agent is unclear but may be due to additives.

** Acute renal failure is most likely to occur when lovastatin is given in combination with cyclosporine. *** Ethylene glycol-induced toxicity can cause calcium oxalate crystals.

FIGURE 11-2

Drugs and chemicals associated with acute renal failure. (Apapted from Thadhani, et al. [2].)

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