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A patient comes to the pharmacy and says that the doctor prescribed her with Naproxen for her kidney stones, and said that it is not only going to reduce pain, but it will also facilitate the passage of the stone.

I was unable to find anything in the literature about such effect of NSAIDs, and moreover, I found this paper that says clearly:

"[NSAIDs] are highly effective in reducing the number of new colic episodes and readmissions to hospital; however they do not appear to have any effect on the time to stone passage or the likelihood of stone passage in renal colic."

The mechanism of action of NSAIDs in the kidneys is also pretty straightforward: NSAIDs inhibit prostaglandins production, which themselves promote glomerular afferent arteriolar vasodilatation. Therefore, the effect of NSAIDs will be opposite, i.e. glomerular afferent arteriolar constriction, which wil certainly not help a kidney stone to pass if it is there.

The patient insists that this is exactly what the doctor told her. Does anyone know any source that will support this claim?

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Non-steroidal anti-inflammatory drugs and the kidneys

You’re right that non-steroidal anti-inflammatory drugs (NSAIDs) have an effect on the glomerular arterioles by inhibiting prostaglandin production. This is why they can be renotoxic; if the affereny arteriole constricts, the filtration pressure drops and this can lead to renal failure in susceptible individuals or those on interacting drugs (like angiotensin converting enzyme (ACE) inhibitors, which dilate the efferent arteriole).

Nephrolithiasis (kidney stones)

However, these arterioles are blood vessels. Kidney stones (renal calculi) form in the nephron or further down the drainage system in the ureters by the precipitation and crystallisation of calcium or oxalate salts.

NSAIDs do reduce excretion of calcium, so it was thought they might reduce the formation of calculi. However, they also reduce secretion of other protective factors (such as glucosaminoglycans, or GAG), so there is no significant overall benefit, other than analgesia.

I found this old paper from the International Journal of Clinical Pharmacology, Therapy and Toxicology that looked at the effects of the NSAID diclofenac in people with hypercalciuria (higher than normal calcium levels in the urine).

Non-steroidal anti-inflammatory drugs decrease urinary calcium excretion in male Sprague-Dawley rats. Indomethacin decreases significantly the urinary calcium excretion in hypercalciuric patients. These observations encouraged the use of NSAID in the treatment of nephrolithiasis with encouraging initial results. However, NSAID (indomethacin and naproxen) retard both glycosaminoglycans (GAGs) synthesis and degradation thereby causing a significant reduction in the urinary excretion of GAGs, known to be potent inhibitors of calcium oxalate crystallization. Therefore, the effect of another NSAID, diclofenac-Na (50 mg t.i.d. for 4 weeks) was studied on 31 recurrent calcium oxalate nephrolithiasis patients who were not hypercalciuric or hyperuricosuric. The 24-h urinary excretion of creatinine, calcium and uric acid remained unchanged at 2 weeks and 4 weeks of therapy. However, after treatment of 2 weeks and 4 weeks, there was a significant decrease in the 24-h urinary excretion of GAGs (from 17.04 +/- 7.39 mumol to 11.54 +/- 7.02 and 12.7 +/- 6.2 mumol, respectively), and urinary concentration of GAGs (from 10.77 +/- 7.09 mumol/l to 6.03 +/- 5.00 mumol/l and 7.35 +/- 4.81 mumol/l, respectively). Thus diclofenac-Na (50 mg t.i.d.) did not reduce urinary excretion of calcium but significantly lowered the urinary excretion and concentration of GAGs in normocalciuric nephrolithiasis patients, an observation which cautions against the use of diclofenac-Na in prevention of nephrolithiasis in this group of patients.

Summary

Thus, the reason NSAIDs are used is for analgesia. They do not have an overall effect to reduce e stone formation and there is no mechanism by which they facilitate the passage of the stone. This is in keeping with current practice on the management of neprolithiasis.

To help facilitate the passage of a stone, alpha adrenoceptor antagonists (like doxazosin) can be used. They relax the smooth muscle surrounding the ureters and urethra, allowing any calculi to pass more easily.


References

A K Hemal, H Sidhu, S K Thind, R Nath, S Vaidyanathan. Effect of diclofenac-Na on 24-hour urinary excretion of creatinine, calcium, uric acid and glycosaminoglycans in adult patients with recurrent calcium oxalate nephrolithiasis. International Journal of Clinical Pharmacology, Therapy, and Toxicology. 1989 Jan; 27 (1) : 44-6.

Conor P Moran, Aisling E Courtney. Managing acute and chronic renal stone disease. Practitioner. 2016 Feb; 260 (1790) : 17-20, 2-3.

Renee R. Koski, PharmD, CACP, FMPA and William H. Zufall, PharmD. Efficacy and Safety of Alpha-Blockers for Kidney Stones in Adults. Journal of Pharmacy Technology, 2018 Apr; 34(2): 54–61. DOI: 10.1177/8755122517750398

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