ObjectiveHigh-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders.Methods and Patients Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination.Results Electrolyte disorders (Na <135 mEqll and/or K>5.0 mEq//) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7±24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7±84.2 mg vs. 101.9±9.38 mg, p=0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP <80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr >1.2 mg/dl), compared with 17.5% of patients with normal renal function (p=0.0008). Logistic regression analysis showed that the dose of TMPand the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2. 35 and 80.29, respectively. Conclusion Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX.These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX. (Internal Medicine 42: 665-669, 2003)

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Glucagon-like peptide-1 (GLP-1) is one of the incretins, gut hormones released from the intestine in response to food intake. GLP-1 receptor (GLP-1R) agonists have been used to treat type 2 diabetes. Here, we studied the effect of the administration of a GLP-1R agonist, liraglutide, on proteinuria and the progression of overt DN in type 2 diabetic patients. Twenty-three type 2 diabetic patients with overt DN, who had already been treated with blockade of renin-angiotensin system under dietary sodium restriction, were given liraglutide for a period of 12 months. Treatment with liraglutide caused a significant decrease in HbA1c from 7.4 ± 0.2% to 6.9 ± 0.3% (p = 0.04), and in body mass index (BMI) from 27.6 ± 0.9 kg/m 2 to 26.5 ± 0.8 kg/m 2 after 12 months (p < 0.001), while systolic blood pressure did not change. The progression of DN was determined as the rate of decline in estimated glomerular filtration rate (eGFR). The 12-month administration of liraglutide caused a significant decrease in proteinuria from 2.53 ± 0.48 g/g creatinine to 1.47 ± 0.28 g/g creatinine (p = 0.002). The administration of liraglutide also substantially diminished the rate of decline in eGFR from 6.6 ± 1.5 mL/min/1.73 m 2 /year to 0.3 ± 1.9 mL/min/1.73 m 2 /year (p = 0.003). Liraglutide can be used not only for reducing HbA1c and BMI, but also for attenuating the progression of nephropathy in type 2 diabetic patients.

We determined the effects of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid intima-media thickness (IMT) and the factors associated with the change in carotid IMT in patients taking a statin. The change in carotid mean and maximum IMT before and after the initiation of evolocumab treatment was retrospectively analyzed in 229 statin-treated patients. The changes in clinical parameters, including serum lipid concentrations, were also evaluated. Evolocumab significantly reduced the increase in carotid mean and maximum IMT (0.09 ± 0.13 mm/year to −0.04 ± 0.16 mm/year, p < 0.001 and 0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p = 0.02). Evolocumab reduced serum total cholesterol, low-density lipoprotein-cholesterol, triglyceride, and lipoprotein (a) concentrations (each p < 0.001), and increased serum high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.01). Multiple linear regression analysis revealed that the change in HDL-cholesterol (standard coefficient (β) = −0.120, p = 0.04) and carotid mean IMT (β = −0.467, p < 0.001) were independently correlated with the change in carotid mean IMT during the administration of evolocumab, whereas the change in HDL-cholesterol (β = −0.208, p = 0.002) and log-triglyceride (β = −0.167, p = 0.01) independently correlated with the change in carotid maximum IMT. Evolocumab reduced the increase in carotid IMT in patients taking a statin. These results suggest that evolocumab is protective against carotid atherosclerosis in patients undergoing statin therapy.

This study investigated the effects of evolocumab on vulnerable coronary plaques and factors associated with the change in stability and size of plaques in patients taking statins. Vulnerable coronary plaques were defined using coronary computed tomography (CT) angiography as having a density of <50 HU within the region of interest and a remodeling index ≥1.1. The changes in minimum CT density, remodeling index, and percent stenosis of vulnerable coronary plaques after six months of evolocumab administration were retrospectively analyzed in 136 vulnerable coronary plaques from 98 patients (68 men and 30 women; mean age: 72.9 ± 8.7 years) treated with a statin. The administration of evolocumab significantly increased the minimum CT density (39.1 ± 8.1 HU to 84.9 ± 31.4 HU, p < 0.001), reduced the remodeling index (1.29 ± 0.11 to 1.19 ± 0.10, p < 0.001), and decreased the percent stenosis (27.0 ± 10.4% to 21.2 ± 9.8%, p < 0.001). Multiple linear regression analysis revealed that baseline percent stenosis (standard coefficient (β) = −0.391, p = 0.002) independently correlated with the change in minimum CT density, whereas the baseline remodeling index (β = −0.368, p < 0.001) independently correlated with a change in the remodeling index. Evolocumab stabilized vulnerable coronary plaques and reduced their size. These results suggest that evolocumab protects against coronary artery disease progression in patients taking statins.

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