Association between medications and urinary PH

Résumé

Background. There are many common disorders/diseases that lead to changes in acid base balance, such as asthma, chronic obstructive pulmonary disease (bronchitis or emphysema), diabetic ketoacidosis, renal disease or failure, any type of shock (sepsis, anaphylaxis, neurogenic, cardiogenic, hypovolemia), stress or anxiety which can lead to hyperventilation, and some drugs (sedatives, opoids) leading to reduced ventilation. Several factors can influence on urine pH: diet, body surface area, acute water load and exercise. A chronic acidic load can cause a number of health conditions such as osteoporosis, kidney disease, and muscle wasting. Acidic urine pH has been suggested to play an important role in human bladder carcinogenesis by influencing the urine concentration of active aromatic amines. Urine pH also plays an important role in the formation of most types of kidney stones. Some medications may also influence on urine pH in either direction. However, to date there are no studies that have evaluated the association between medication use and urine pH. Considering these premises, the present thesis focused on the association between medication use after hospital discharge in a population from the control group of a case -control study of bladder cancer and having constantly acidic urine pH. Methods. Data collection for this research has been taken from a case-control study on bladder cancer. We have limited subject inclusion and statistical analyses for this report to the control subjects of the case-control study. In the case-control study, 1219 incident transitional cell carcinoma (TCC) cases (84% of 1453 contacted cases) and 1271 hospital controls (88% of 1442 controls) were recruited between June 1998 and June 2001 in 18 hospitals in the following regions in Spain: Barcelona, Vailes/Bages, Asturias, Alicante, and Tenerife. Subjects were 21 to 80 years old at the time of diagnosis and resided in the catchment areas of the 18 participating hospitals. Out of the 611 control subjects with available valid pH measurements, 598 (97.87%) subjects reported information on vitamins and medications use, and after excluding two subjects with low quality of the interview, and 175 subjects with missing information in the potential cofounders (vegetable intake (n�18), fruit intake (n=15), meat intake (n-89), height (n=85), and weight (n-70), (one subject can have missing information in more than one variable)) we ended with 423 subjects, which is the base population used for this report. Study participants were trained to test their urine pH with dipsticks twice a day at home (first void in the morning and early in the evening) during 4 consecutive days two weeks after hospital discharge, recording results into a diary together with all medications taken during each of the four days of pH measurements. To estimate the effects of medication on urinary pH, we calculated odds ratios (OR) and 95% confidence intervals (95% Cl) using unconditional logistic regression, with two strategies: a) Fixed terms entered for alf potential confounding variables (i.e., age at interview, sex, study region, vegetable intake, fruit intake, meat intake, height, weight, and vitamin C use) plus the medication of interest, building one modei for each medication at the segregation levels of 1, 3, 4, 5, and 7 digits of the ATC classification; and b) fixed terms strategy (for all potential confounding factors) combined with step wise strategy entering all medications from a given segregation level of the ATC Classification. Results. We found statistically significant associations between some medications used bv our study population and their influence on urine pH levels: �cardiac glycosides" {OR=7.533, 95%CI: 1.63 ~ 34.71), drugs acting on �respiratory system� (OR=0.23, 95%Ci: 0,07 ~ 0.81) and �psycholeptics� (OR=0.35, 95%CI: 0.12 - 0.96), that mostly included "anxiolytics� {OR=0.164, 95%CI: 0.041 - 0.647). Conclusions. Plausible mechanisms discussed, to explain the association between cardiac glycosides with having constantly acidic urine pH could include: the effect of the underlying cardiac diseases for which these drugs are prescribed for, and the direct effect from such drugs on urine pH. The association between anxiolytics with not having constantly acidic urine pH would most likely represents the effect of the hyperventilation generated from the underline anxiety disorder for which these drugs are prescribed, rather than a direct effect from such drugs on urine pH. The association between drugs used in the respiratory system and not having constantly acidic urine pH could be explained by some states of chronic airway diseases, and by the direct effect from these drugs on urine pH