Drug-Induced Nephrotoxicity Aetiology, Clinical Features and Management

Abstract

There is a growing number of hospitalised patients who develop a drug-induced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. The 3 clinical syndromes that can be recognised in drug-induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. The first can be caused by prerenal problems, acute interstitial nephritis, acute tubular necrosis and intratubular obstruction. The most important drugs that cause prerenal failure are NSAIDs, captopril and cyclosporin. NSAIDs inhibit the synthesis of prostaglandins, and consequently vasoconstriction of the afferent arteriole leads to lowering of the glomerular filtration rate (GFR); captopril blocks the formation of angiotensin II (which also leads to a lower GFR), and should be used with caution in patients with stenotic renal arteries; cyclosporin causes vasoconstriction of the afferent arteriole, which is probably mediated by the sympathetic system. Combinations of these drugs result in increased nephrotoxicity. The drugs most likely to cause acute interstitial nephritis are antibiotics and NSAIDs. Normally, signs of an allergic reaction are also present. Acute interstitial nephritis is usually self-limiting, but in some studies it is claimed that steroids may promote recovery. Four important causal agents of acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents and cyclosporin. Approximately half of the cases of drug-induced renal failure are related to the use of aminoglycosides: generally, 10 days after start of treatment a nonoliguric renal failure develops, with recovery after withdrawal of the drug in almost all cases. The aminoglycosides are particularly nephrotoxic when combined with other nephrotoxic drugs. 80% of amphotericin B-treated patients develop renal insufficiency, a percentage that increases as the cumulative dose exceeds 5g. It is because of its unique antifungal properties that there are still some indications for the use of this highly nephrotoxic drug; the high percentage of nephrotoxicity can probably be prevented in part by sodium loading. The nephrotoxicity of radiocontrast agents is largely dependent on renal function: from 0.6% in patients with normal renal function to 100% in patients with a serum creatinine above 400 mumol/L. Diabetes mellitus does not add greatly to the risk of radiocontrast nephrotoxicity. The nephrotoxicity of cyclosporin is dose-dependent and reversible, although there are some reports of irreversibility after long term use. Cyclosporin can also result in nephrotoxicity in combination therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Pyrimethamine inhibits renal secretion of creatinine

“…Pyrimethamine has not been associated with any typical renal side effects (10,20), even though it has been in clinical use for many years. Our study demonstrates for the first time that moderate but consistent rises in serum creatinine occurred after the administration of a single dose of 100 mg of pyrimethamine in persons without any known kidney disease.…”

“…This treatment used weekly combined doses of pyrimethamine and dapsone for prophylaxis of human immunodeficiency virus (HIV)-associated Pneumocystis cannii pneumonia and cerebral toxoplasmosis (19). Both drugs have only rarely been associated with renal side effects and do not belong to groups of typically nephrotoxic agents (10,20). Reduction in glomerular filtration rate can occur as a consequence of a drug-induced nephropathy, including acute tubular necrosis, interstitial nephritis, and intratubular obstruction (10,20).…”

“…Both drugs have only rarely been associated with renal side effects and do not belong to groups of typically nephrotoxic agents (10,20). Reduction in glomerular filtration rate can occur as a consequence of a drug-induced nephropathy, including acute tubular necrosis, interstitial nephritis, and intratubular obstruction (10,20). On the other hand, certain drugs, such as cimetidine, trimethoprim, and probenecid, have been shown to reduce tubular secretion of creatinine without causing a reduction in glomerular filtration rate (5,8,9,18,24).…”

Enzymatic and Non Enzymatic Antioxidant Activity of Tabernaemontana divaricate R.Br. Against DEN and Fe-NTA Induced Renal Damage in Wistar Albino Rats

“…subacute renal proximal tubular necrosis by catalyzing the decomposition of H 2 O 2 -derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage (Iqbal et al, 2010). A number of therapeutic agents can adversely affect the kidney resulting in acute renal failure, chronic interstitial nephritis and nephritic syndrome because there is an increasing number of effective therapeutic drugs like aminoglycoside antibiotics, NSAID's, chemotherapeutic agents have been added to the therapeutic arsenal in recent years (Hoitsma et al, 1991). India is endowed with a rich wealth of medicinal plants.…”

Massive Proteinuria: A Possible Side Effect of Pyrantel Pamoate?

“…The three recognizable drug-induced clinical syndromes are acute renal failure, chronic interstitial nephritis, and NS. 5,6 Several drugs such as aminoglycosides, amphotericin B, radiocontrast agents, and cyclosporine have already been identified as causal agents of acute tubular necrosis, but no data exist about the potential renal toxicity due to anthelmintics administration.…”