Association of urinary citrate excretion, pH, and net gastrointestinal alkali absorption with diet, diuretic use, and blood glucose concentration

Abstract

Urinary citrate (Ucit) protects against urinary stone formation. Acid base status and diet influence Ucit. However, the effect of demographics, diet, and glucose metabolism on Ucit excretion, urinary pH (U‐pH) and net gastrointestinal alkali absorption (NAA) are not known. Twenty‐four hour urine samples, blood glucose, creatinine, and cystatin C were obtained from non‐Hispanic white sibships in Rochester, MN (n = 446; 64.5 ± 9 years; 58% female). Diet was assessed by a food frequency questionnaire. The impact of blood glucose, demographics and dietary elements on Ucit excretion, U‐pH, and NAA were evaluated in bivariate and multivariable models and interaction models that included age, sex, and weight. NAA significantly associated with Ucit and U‐pH. In multivariate models Ucit increased with age, weight, eGFRC ys, and blood glucose, but decreased with loop diuretic and thiazide use. U‐pH decreased with serum creatinine, blood glucose, and dietary protein but increased with dietary potassium. NAA was higher in males and increased with age, weight, eGFRC ys and dietary potassium. Significant interactions were observed for Ucit excretion with age and blood glucose, weight and eGFRC ys, and sex and thiazide use. Blood glucose had a significant and independent effect on U‐pH and also Ucit. This study provides the first evidence that blood glucose could influence urinary stone risk independent of urinary pH, potentially providing new insight into the association of obesity and urinary stone disease.

Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones

“…In a study on 446 participants (11.5% of whom were with a history of kidney stones), Perinpam et al found that net gastrointestinal alkali absorption was directly associated with urine pH and citrate, similar to our findings; however, that study only partially accounted for differences in dietary acid load by adjustment for dietary potassium intake and did not analyze differences between the (very few) stone formers and non–stone formers. 7 Sakhaee et al reported a direct association between net gastrointestinal alkali absorption and urine citrate in 131 non–stone formers and in idiopathic hypocitraturic stone formers, but not in patients affected by distal renal tubular acidosis. However, in that study, the authors did not control for differences in dietary intakes, and in fact, net gastrointestinal alkali absorption was used as a marker of dietary intake of potential alkali.…”

“…Alternatively, it could be hypothesized that the Oh equation for net gastrointestinal alkali absorption estimation is not valid in stone formers because it incorporates urine chemistries that are known to be altered in those with kidney stones, such as calcium, potassium, magnesium, and phosphate. However, this approach has been used in the past to study net gastrointestinal alkali absorption in stone formers, 7,8 and balance studies on stool are difficult to perform. Furthermore, the relationship in the expected direction between net gastrointestinal alkali absorption and both urine pH and renal net acid excretion, which are not included in the calculation of net gastrointestinal alkali absorption, strengthens the validity of the net gastrointestinal alkali absorption calculation.…”

Furosemide Diuretic Activity Evaluation in Female Sprague-Dawley Rats

“…The above is due to the expansion of the aqueous urinary volume, which gives the activation of the sodium-hydrogen-ATPase antiporter, producing a hydrogen secretion and passive bicarbonate reabsorption. In the case of the Furosemide group, occurred an exchange of sodium and chlorine for hydrogenation in the collecting tubule, causing a slightly more acidic pH [14].…”