BackgroundDapagliflozin inhibits the sodium‐glucose–linked transporter 2 in the renal proximal tubule, thereby promoting glycosuria to reduce hyperglycemia in type 2 diabetes mellitus. Because these patients may require loop diuretics, and sodium‐glucose–linked transporter 2 inhibition causes an osmotic diuresis, we evaluated the diuretic interaction between dapagliflozin and bumetanide.Methods and ResultsHealthy subjects (n=42) receiving a fixed diet with ≈110 mmol·d−1 of Na+ were randomized to bumetanide (1 mg·d−1), dapagliflozin (10 mg·d−1), or both for 7 days, followed by 7 days of both. There were no meaningful pharmacokinetic interactions. Na+ excretion increased modestly with the first dose of dapagliflozin (22±6 mmol·d−1; P<0.005) but by more (P<0.005) with the first dose of bumetanide (74±7 mmol·d−1; P<0.005), which was not significantly different from both diuretics together (80±5 mmol·d−1; P<0.005). However, Na+ excretion with dapagliflozin was 190% greater (P<0.005) when added after 1 week of bumetanide (64±6 mmol·d−1), and Na+ excretion with bumetanide was 36% greater (P<0.005) when added after 1 week of dapagliflozin (101±8 mmol·d−1). Serum urate was increased 4% by bumetanide but reduced 40% by dapagliflozin or 20% by combined therapy (P<0.05).ConclusionsFirst‐dose Na+ excretion with bumetanide and dapagliflozin is not additive, but the weekly administration of one diuretic enhances the initial Na+ excretion with the other, thereby demonstrating mutual adaptive natriuretic synergy. Combined therapy reverses bumetanide‐induced hyperuricemia. This requires further study in diabetic patients with hyperglycemia who have enhanced glycosuria and natriuresis with dapagliflozin.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00930865.
Purpose To determine the relationship between diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in patients with acute stroke at admission and the tissue outcome 1 month after onset of stroke. Materials and Methods Patients with stroke underwent DWI (b values = 0, 1000 sec/mm along three directions) and DKI (b values = 0, 1000, 2000 sec/mm along 20 directions) within 24 hours after symptom onset and 1 month after symptom onset. For large lesions (diameter ≥ 1 cm), acute lesion volumes at DWI and DKI were compared with those at follow-up T2-weighted imaging by using Spearman correlation analysis. For small lesions (diameter < 1 cm), the number of acute lesions at DWI and DKI and follow-up T2-weighted imaging was counted and compared by using the McNemar test. Results Thirty-seven patients (mean age, 58 years; range, 35-82 years) were included. There were 32 large lesions and 138 small lesions. For large lesions, the volumes of acute lesions on kurtosis maps showed no difference from those on 1-month follow-up T2-weighted images (P = .532), with a higher correlation coefficient than those on the apparent diffusion coefficient and mean diffusivity maps (R = 0.730 vs 0.479 and 0.429). For small lesions, the number of acute lesions on DKI, but not on DWI, images was consistent with that on the follow-up T2-weighted images (P = .125). Conclusion DKI complements DWI for improved prediction of outcome of acute ischemic stroke. RSNA, 2018.
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