26th June 2023

Drug-induced nephropathy

Mechanism of nephrotoxicity

Pre-renal AKI

The kidney autoregulates intraglomerular pressure via the afferent and efferent arterioles to maintain glomerular filtration rate (GFR) and urine output. Circulating prostaglandins vasodilate the afferent arterioles, and angiotensin-II mediates vasoconstriction of the efferent arteriole, both actions increasing GFR. Drugs with anti-prostaglandin activity, such as nonsteroidal anti-inflammatory drugs (NSAIDs), or those with anti-angiotensin-II activity, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can interfere with the kidneys’ ability to autoregulate glomerular pressure and decrease GFR. Therefore these drugs can worsen a pre-renal acute kidney injury (AKI).

Acute Tubular Necrosis

Renal tubular cells are vulnerable to drug toxicity as the filtrate is very concentrated at this point in the nephron. Acute tubular necrosis (ATN) is typically mediated by the actions of drugs on mitochondrial function, interfering with tubular transport, increasing oxidative stress, or forming free radicals. Examples of such drugs are aminoglycosides, amphotericin B, antiretrovirals, cisplatin and contrast dye. Rhabdomyolysis leads to the filtration of myoglobin which acts as a nephrotoxin in a similar way.

Acute Interstitial Nephritis

Acute interstitial nephritis tends to occur as an allergic response to a drug in a non–dose-dependent fashion. The drug is thought to bind to antigens in the kidney or act as antigens that are then deposited into the interstitium, inducing an immune reaction. However, classic symptoms of a hypersensitivity reaction (i.e., fever, rash, and eosinophilia) are not always observed. Numerous drugs have been implicated, including allopurinol; antibiotics such as penicillins, cephalosporins, sulphonamides and ciprofloxacin; NSAIDs; diuretics such as furosemide or thiazides; phenytoin; proton pump inhibitors.

Prescribing in Kidney Disease

Many drugs and their metabolites are excreted from the body via the kidneys; this can be by glomerular filtration and/or secretion in the tubules. Therefore, in the presence of renal dysfunction, the clearance of renally-excreted drugs can be impaired, leading to prolonged half-life and accumulation of the drug or metabolites with potentially significant clinical consequences. It is important to be cautious when prescribing in renal impairment, as reduced doses or increased dosing intervals of drugs may be required. The BNF and The Renal Drug Handbook are useful tools to aid prescribing in acute or chronic renal disease.