Indomethacin nephrotoxicity

Diuretics NSAIDs cause sodium retention and reduce diuretic and antihypertensive efficacy risk of hyperkalaemia with potassium-sparing diuretics increased nephrotoxicity risk (with indomethacin, ketorolac). 

Triamterene has been reported to cause photosensitivity reactions, increase in uric acid concentration, and blood dyscrasias.91 Nephrolithiasis may occur in susceptible patients. Megaloblastic anemia has been reported in patients with depleted folic acid stores such as those with hepatic cirrhosis. In a study conducted on rats, daily treatment of the animals with doses of 1.5, 3 and 4.5 mg/lOOg over the period of three weeks caused severe degenerative changes of renal cortical and medullary tubules resembling osmotic nephrosis.93 Reversible acute renal failure from combined triamterene and indomethacin in healthy subjects is reported.94 It is recommended that this potentially nephrotoxic association be avoided. 

NSAIDs probably rednce proteinnria throngh prostaglandin E2 inhibition, resulting in a rednction of intraglomemlar pressure, a decrease in GER, and also restoration of the barrier size-selectivity of the GBM. Indomethacin and meclofenamate are the two NSAIDs that have been evalnated the most. Their antiproteinuric effect is comparable to those attained with ACEIs, and combined treatment with an ACEI results in additional proteinnria rednction. However, adherence to a low-sodinm diet or concnrrent nse of a dinretic is needed to maximize the antiproteinuric effect. Due to their potential for nephrotoxicity, especially in patients with poor renal fnnction, long-term use of an NSAID for renoprotection is not preferred. ... 

Indomethacin (Indocin) Contraindicated in patients with Gl lesions. May worsen pre-existing depression, epilepsy or Parkinson s disease. Most likely to be nephrotoxic. Also indicated to close patent ductus arteriosus in newborns. 

As indomethacin has several undesirable side effects such as gastrointestinal bleeding, platelet dysfunction and nephrotoxicity, it is not routinely recommended for use in ALF patients in spite of the positive effects observed. 

RPA-1 is a glycoprotein that has only been identified in the rat and generally localized to the collecting duct of kidney. The structure and function of RPA-1 are undetermined (Shaw, 2010). In rats, RPA-1 increased in urine and kidney tissue after treatment with nephrotoxic compounds (e.g., propyle-neimine, indomethacin). Recently, RPA-1 was qualified for coUeeting duct injury in rats, but the human equivalent is unknown (Hildebrand et al., 1999 Price et al., 2010). 

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