Comparisons of Therapeutic Effects of Allopurinol and Febuxostat in Chronic Hemodialysis Patients

More than few patients on maintenance hemodialysis present with hyperuricemia, and the control of serum uric acid level is an important issue in the long-term management. In addition to allopurinol, febuxostat can be used as a xanthine oxidase inhibitor in hemodialysis patients. In this study, the clinical effects of febuxostat were compared with allopurinol in chronic hemodialysis patients. Eligible hemodialysis patients taking allopurinol were randomly assigned to take 100 mg allopurinol（n＝26）or 20 mg febuxostat（n＝23）for 12 weeks. Serum uric acid was markedly lowered in the febuxostat group（0-week 6.7 mg/dL, 12-week 4.3 mg/dL, p＜0.001）as compared with the allopurinol group（0-week 6.0 mg/dL, 12-week 5.8 mg/dL）and systolic blood pressure was lowered by 5 mmHg（p＝0.036）at 4-week in the febuxostat group while blood pressure was not significantly changed in the allopurinol group throughout the study period. In addition, the dose of erythropoiesis stimulating agent was reduced（0-week 22.2 μg/wk, 12-week, 17.1 μg/wk, p＝0.012）and serum phosphate level was lowered（0-week 5.9 mg/dL, 12-week 5.1 mg/dL, p＝0.027）in the febuxostat group but not in the allopurinol group. It is concluded that febuxostat is more effective in lowering serum uric acid than allopurinol in hemodialysis patients. In addition, it is suggested that febuxostat has an advantage in the management of renal anemia and hyperphosphatemia as well as hyperuricemia

Therapeutic Effects of a Sodium Glucose Cotransporter 2 Inhibitor in Diabetic Patients with Chronic Kidney Disease

Multiple large-scale clinical trials have indicated that sodium glucose cotransporter 2（SGLT2）inhibitors reduce the incidence of cardiovascular events, deterioration of renal function and mortality. However, the therapeutic effects of SGLT2 inhibitors are supposed to be limited in patients with reduced renal function considering the mechanism of their action. In this study, a SGLT2 inhibitor, ipragliflozin was given to 30 type 2 diabetic patients with nephropathy whose estimated glomerular filtration rate（eGFR）was not lower than 30 mL/min/1.73 m2. After 12 to 16 weeks, hemoglobin A1c decreased by 0.6％（p＜0.001）, body weight was reduced by 1.8 kg（p＜0.01）and blood pressure was lowered by －10/－6 mmHg（p＜0.001/p ＜0.001）. This was accompanied by reductions in serum uric acid（－0.7 mg/dL, p＜0.001）, triglycerides （－25 mg/dL, p＝0.028）and g-glutamyl transferase（－8 U/L, p＝0.001）. On the other hand, plasma B-type natriuretic peptide also decreased by 12％（p＝0.020）and urinary albumin excretion was reduced by 23％ （p＝0.018）although the eGFR was not significantly changed. It is concluded that ipragliflozin is effective in lowering blood glucose even in patients with diabetic kidney disease and is beneficial in improving theaccompanying obesity and hypertension. In addition, ipragliflozin is thought to have favorable influences on the metabolisms of uric acid and lipids. These properties of ipragliflozin is expected to bring about protective effects against the progression of nephropathy and the development of cardiovascular disease resulting in the improvement of prognosis in diabetic patients with mild to moderate chronic kidney disease

Comparisons of Increasing Calcium Channel Blocker dose and Adding Thiazide Diuretic in Hypertensive Patients Given Medium-dose Angiotensin II Receptor Blocker and Amlodipine

We compared the efficacies of 2 prescriptions, one of a medium-dose angiotensin II receptor blocker （ARB） with high-dose of calcium channel blocker （CCB） and another of medium-dose of ARB with medium-dose of CCB and a thiazide diuretic in 22 hypertensive patients who did not achieve the target blood pressure level with the combination of medium-dose of ARB and medium-dose of CCB. A randomized crossover study was performed giving a fixed combination of 100 mg irbesartan with 10 mg amlodipine or a fixed-dose combination of 100 mg irbesartan with 5 mg amlodipine added by 1 mg trichlormethiazide for 12-16 weeks each. The blood pressure measured in hospital was comparable between the high-dose CCB period （130/77 mmHg） and the thiazide period （130/79 mmHg）. The morning and the evening blood pressures measured at home were also comparable in the high-dose of CCB and the thiazide periods, while the evening heart rate was higher in the thiazide period than in the high-dose CCB period. As for the laboratory data, hemoglobin A1c （＋0.2％, p＝0.013）, serum nonHDL cholesterol （＋12 mg/dL, p＝0.047） and serum uric acid （＋0.8 mg/dL, p＝0.001） were significantly higher in the thiazide period than in the high-dose CCB period. On the other hand, urinary albumin excretion （－28.8％，p＝0.026） and estimated glomerular filtration rate （－5.8％，p＝0.012） were significantly lower in the thiazide period than in the high-dose CCB period. In the combination drug therapy of hypertension, the increase of CCB dose is preferable in preserving renal function and in avoiding adverse effects on metabolisms of glucose, lipid and uric acid