NSAIDs have a damaging effect on the kidneys; they can cause urinary protein, tubularity and the appearance of red blood cells in the urine. Very few patients develop acute interstitial nephritis and lead to nephrotic syndrome. NSAIDs inhibit the production of prostaglandin E in the body, which has a powerful vasodilating effect, so NSAIDs can reduce blood perfusion to the kidney. The use of NSAIDs in patients with renal insufficiency caused by diabetes, hypertension, and cirrhosis can worsen renal failure. Renal damage rarely occurs with NSAIDs at typical doses. Aspirin alone has rarely induced serious kidney damage, but compounded aspirin (containing finasteride and caffeine) has been reported in a large number of cases of kidney disease and has almost become a social problem. Other NSAIDs, such as anti-inflammatory pain, ibuprofen, naproxen, and protamine, have been shown to be nephrotoxic. To avoid renal damage from NSAIDs, they should be used with caution in the elderly and in patients with existing kidney disease. Sulindac (Chironolactone) has less renal damage. A controlled study with ibuprofen found that in patients with chronic glomerulopathy, Chironolactone had no effect on the clearance of creatinine and para-aminomaluric acid in the kidney. Because the drug is metabolized to active sulfide in the body, this sulfide is oxidized to inactive precursors in the kidney, thus not affecting the renal cyclooxygenase, so prostaglandin synthesis is not inhibited, and renal blood flow and glomerular filtration rate are not changed, so the drug is safer for the elderly.