Naproxen and sulindac improved symptoms of chronic inflammatory joint disease, but naproxen inhibited renal filtration, renal flow, and renal endocrine functions
ACP J Club. 1991 Jan-Feb;114:16. doi:10.7326/ACPJC-1991-114-1-016
Eriksson LO, Sturfelt G, Thysell H, Wollheim FA. The effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. Am J Med. 1990;89:313-21.
To compare the effects of sulindac and naproxen on renal function in patients with rheumatoid arthritis and stable but impaired kidney function. The efficacy of these drugs over the period of the study was also tested.
Randomized, double-blind, placebo-controlled, crossover trial. All patients were followed for the 28 days of the trial.
The study was done in Lund, Sweden. [The referral pattern was not reported.]
The study enrolled 9 patients with stable classical or definite rheumatoid arthritis and 1 with ankylosing spondylitis. The 8 female and 2 male patients were aged between 39 and 77 years. All had chronic renal disease (range 1 to 11 y), from various causes, established by renal biopsy. The median duration of arthritis was 18 years (range 6 to 32 y).
Patients were instructed to discontinue all NSAIDs and were given placebo instead. After 4 days they were hospitalized for 3 days, and fasting baseline samples were collected. For the next 7 days they were randomized to sulindac (200 mg at 0800 hours and 2000 hours) or naproxen (500 mg at 0800 hours and 250 mg at 2000 hours) and rehospitalized for 3 days. The 14-day cycle was repeated with patients receiving the alternate medication for 7 days.
Main outcome measures
Effects on kidney function were measured through repeated urine and blood sampling, changes in body weight, and cumulative urine volume. Clinical efficacy was measured by the Ritchie articular index and grip strength.
During treatment with naproxen, glomerular filtration rate decreased by 18% and renal plasma flow by 13%. Both rates were lower than rates with placebo (P < 0.05). No change in these rates occurred with sulindac. Renal endocrine production was also diminished by naproxen; a decrease of 59% occurred in prostaglandin synthesis (P < 0.01) and 38% for plasma renin activity (P < 0.05). Sulindac also decreased plasma renin activity by 22% (P < 0.05). Grip strength and Ritchie articular index improved, grip strength significantly (P < 0.05), for both NSAIDs when compared with placebo.
Over 7 days, naproxen had more inhibiting effects on renal endocrine functions, renal filtration, and renal flow than did sulindac. Naproxen and sulindac both improved symptoms of chronic inflammatory joint disease.
Sources of funding: University of Lund and Merck Sharp & Dohme.
Address for article reprint: Dr. L. O. Eriksson, Department of Clinical Pharmacology, Lund University Hospital, S-221 85, Lund, Sweden.
From a rheumatology perspective: NSAIDs have become the treatment of choice for the management of many rheumatic conditions, and elderly persons are among the most frequent users of these medications. Although the mechanisms of anti-inflammatory action of NSAIDs are multiple, prostaglandin blockade is responsible for many of their known side effects. Serious gastrointestinal complications, such as bleeding, perforation, or gastric ulcers requiring hospitalization, are increasingly being recognized. Their frequency, morbidity, mortality, and associated risk factors are the subject of numerous ongoing investigations.
NSAID-associated renal dysfunction is also a concern. This report is 1 of a recently published series that documents the "renal sparing effects" of sulindac compared with other NSAIDS. It shows that short-term administration of sulindac does not affect renal prostaglandin synthesis, glomerular filtration rate, and renal blood flow. Whether these properties would persist with long-term therapy needs to be documented.
Claire Bombardier, MD, PhD
Wellesley HospitalToronto, Ontario, Canada
From a nephrology perspective: The laboratory methods used in this paper were excellent, and the study design was good, although the number of patients was small. Sulindac and naproxen usually are used on a long-term basis, and it is important to bear in mind that this study did not assess their long-term effects on renal function. In the short term, neither drug increased the serum creatinine level, the clinical standard for estimating renal function. Even creatinine clearance may not reflect small changes in renal function, and newer isotope techniques may need to be used.
The renal function of patients with chronic renal failure who require NSAIDs should still be carefully monitored, whether they are taking sulindac or naproxen.
M. Arif Manuel, MD
Sunnybrook HospitalToronto, Ontario, Canada