Impact of solute carrier transporter gene polymorphisms on serum creatinine concentrations in healthy volunteers.

In this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is, SLC22A7 c.1586 + 206A > G, SLC22A2 c.808G > T, SLC22A3 c.1233G > A, SLC47A1 c.922-158G > A, and SLC47A2 c.-130G > A, on serum creatinine (SCr) concentrations. This cross-sectional study included residents who participated as volunteers in a health promotion study. Lifestyle data, blood chemical analysis data, and SLC gene polymorphism information were collected from each participant. Univariate analyses were carried out to determine differences between groups and correlations in SCr. Stepwise multiple regression analysis was performed to confirm the independence of factors that were significantly different in the univariate analyses. In multiple regression analyses, muscle mass, serum cystatin C concentrations, body fat percentage, serum albumin concentrations, and SLC47A2 c.-130G/G had the highest contribution to SCr concentrations, in that order (standardized regression coefficients = .505, .332, -.234, .123, and .084, respectively). The final model explained 72.2% of the variability in SCr concentrations. The SLC47A2 c.-130G > A polymorphism may affect creatinine dynamics in the proximal tubules. Further studies are needed to determine the effects of SLC transporter gene polymorphisms on SCr concentrations in patients with various diseases in real-world clinical settings.

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim-sulfamethoxazole without changes in glomerular filtration rate.

WHAT IS KNOWN AND OBJECTIVE: Trimethoprim (TMP) inhibits the Na+ /K+ -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na+ ), and serum potassium (K+ ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR). METHODS: In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded. RESULTS AND DISCUSSION: In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na+ , and K+ concentrations (ΔSCr, ΔNa+ , and ΔK+ ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP. There were significant correlations between ΔSCr and ΔNa+ or ΔK+ (ρ = -0.199, p = 0.036 and ρ = 0.244, p = 0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p = 0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na+ , and K+ in the proximal and distal tubules in a dose-dependent without changing the GFR. WHAT IS NEW AND CONCLUSION: This study is the first report to demonstrate the degree of changes in SCr, Na+ , and K+ concentrations after initiation of TMP-SMX treatment. If SCr is elevated after initiation of TMP-SMX treatment, clinicians should be aware of decreased Na+ and increased K+ concentrations. TMP may increase the risks of hyponatremia and hyperkalemia in a dose-dependent manner without altering GFR.