BERKELEY, CA (UroToday.com) - In calcium oxalate urolithiasis, the monohydrate and dihydrate forms can be found. It has been proved that the main aetiological factors between these groups are different. Thus, calcium oxalate monohydrate (COM) was observed not only to be more frequent in normocalciuric patients but also to be associated with a lack of inhibitory capacity (hypocitraturia) and hiperoxaluria, whereas a mixed calculus of calcium oxalate and phosphate or calcium oxalate dihydrate (COD) can be related to hypercalciuria (Conte et al., Urol Int 1990; 45:25-7). COD renal calculi constitute the most prevalent and recurrent type of renal lithiasis (Grases et al., Scand J Urol Nephrol2003;37:482-6). Different drugs have been used for treating patients with hypercalciuria: sodium cellulose phosphate, orthophosphate, thiazides, and thiazide-like diuretics. These compounds have resulted in various effects and side-effects.
Indapamide is a diuretic compound that was developed for the treatment of hypertension (Milliez and Tcherdakoff, Curr Med Res Opin 1975;3:9-15). The chemical structure of this substance (sulphonamide group) differs from that of thiazide group derivatives used as diuretics. Nevertheless, both indapamide and thiazide diuretics exert similar actions on the kidney (Laubie and Schmitt, Curr Med Res Opin 1977;5:89-100).
|"..indapamide would appear to be a good candidate for use in the control of hypercalciuria in patients without sensitivity to sulphonamides."|
This article presents the results of a pilot study examining the effects of short-term (6 month) and long-term (18 month) treatments with indapamide sustained release, a new specialized dosage form, at a dose of 1.5 mg/day. The aim of this study was to determine the relative hypercalciuric effects of this new dosage form at these two time-points. In addition, we screened patients for any adverse side effects that might be associated with these treatments. Subjects submitted urine and blood samples for analysis. These included a 2 h urine sample as well as the collection of 24 h urine. The administration of 1.5 mg/day of indapamide for 6 months resulted in statistically significant decreases in urinary calcium concentrations. For 2 h urine, there was a 47 % mean decrease of urinary calcium concentration, whereas it decreased by 53% in 24 h urine (p <0.05). Values for the remaining parameters remained unaltered, with the exception of blood urate levels, which rose by 19% (p <0.05). During long-term treatment for 18 months, urinary calcium remained low. In addition, calcium excretion was significantly reduced by approximately 48% (p <0.05), in both 2 and 24 h urine despite individual variations in urine volume. Other measured parameters did not exhibit significant changes, with the exception of urate levels in the blood. A 21% increase in the level of urate was observed (p <0.05), which is in agreement with the results obtained for patients after 6 months of treatment. The results of the present study demonstrate that a low dosage of indapamide sustained release (1.5 mg/day) is effective for the treatment of idiopathic hypercalciuria in COD lithiasic patients. Furthermore, this effect was observed following both short- and long-term treatment periods (18 month). The patients were stone free during this long period of treatment.
It is important to note that indapamide did not cause serious side-effects in the patients in this study. Since indapam ide is a good hypertensive agent, this drug offers the dual benefits of being effective for the treatment of both hypertension and hypercalciuria. Thus, this could potentially reduce drug requirements for patients with both of these conditions. Owing to the possible uricaemic effect, it is recommended that levels of urate in the blood should be monitored and controlled in patients treated with this drug. Indapamide and thiazide diuretics exert similar effects on kidney function. Since thiazide diuretics are known to alter sodium balance, it is possible that indapamide has a similar mode of action in affecting calcium excretion. Owing to the low effective dosage of the drug (1.5 mg/day) and the lack of any severe side-effects, indapamide would appear to be a good candidate for use in the control of hypercalciuria in patients without sensitivity to sulphonamides. As such, it could prove efficacious in the prevention of recurrent kidney stones, which are often associated with hypercalciuria.
Felix Grases and Rafel M. Prieto as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.