Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers

Abstract

The spectrum of diseases with overactive renin–angiotensin–aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography–mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (β: 0.0027; p = 4.2 × 10–7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (β: 0.0022; p = 2.1 × 10–5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.

Comparison of the Effects of Laparoscopic Surgery and Traditional Open Surgery on Stone Clearance, Laboratory Indexes and Life Quality in Patients with Renal Calculi

“…The main incidence group of kidney stone is young and middle-aged male [ 5 ]. However, the incidence of kidney stone in male group is much higher than that in female group [ 6 , 7 ]. For this kind of patients, the stones in the body are mainly removed by operation, while the patients with complex kidney stones are mostly treated by open surgery.…”

Fgf23 expression increases atherosclerotic plaque burden in maleApoEdeficient mice

“…Circulating FGF23 concentrations are inversely correlated to renal function and are recognized as a potential uremic toxin that promotes cardiovascular disease. FGF23 concentrations correlate with endothelial dysfunction, activation of the renin angiotensin aldosterone system, heart failure and adverse clinical outcomes across a broad range of renal function including patients on dialysis treatment (3)(4)(5)(6)(7)(8).…”

Simultaneous quantitation of urine aldosterone and tetrahydroaldosterone in healthy Chinese subjects using a validated LC–MS/MS method

“…Similarly, UTHA has been measured using radioimmunoassay since the 1970s (Delassalle et al, 1977; Kohl et al, 1978; Lewicka & Vecsei, 1985). Different UTHA assays based on GC–MS have recently been published (Ackermann et al, 2019; Dhayat et al, 2015; Moor et al, 2022). Mass spectrometric methods are preferred over immunoassay due to higher sensitivity and specificity (Moor et al, 2022; Yin et al, 2019).…”

“…Different UTHA assays based on GC–MS have recently been published (Ackermann et al, 2019; Dhayat et al, 2015; Moor et al, 2022). Mass spectrometric methods are preferred over immunoassay due to higher sensitivity and specificity (Moor et al, 2022; Yin et al, 2019).…”