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Background In cohort studies of hyperphosphatemic hemodialysis patients, reduced serum phosphate levels have been linked to a lower mortality risk. To investigate whether this benefit is influenced by patient characteristics, we calculated the number needed to be exposed (NNE), stratified by patient characteristics. Methods In this 9-year prospective cohort study using the nationwide Japanese registry, we enrolled 78 256 hemodialysis patients aged 18 years or older. We investigated the relationship between time-averaged (TA) phosphate levels and mortality due to cardiovascular disease (CVD) using Cox proportional models. We estimated the 1-year NNE for CVD death in patients with baseline serum phosphate levels ≥6.0 mg/dL and exposure to TA phosphate levels decreasing to 3.5–<5.0 mg/dL using mixed-effects Poisson models. Results The hazard ratio of CVD mortality decreased linearly with lower serum TA phosphate levels in those with prior atherosclerotic CVD (ACVD) or diabetic nephropathy (DN) but plateaued with serum phosphate <5.0 mg/dL in those without. The hazard ratios (95% confidence interval) for phosphate ≥7.0 mg/dL compared with 3.5–<3.9 mg/dL were 1.58 (1.38–1.81) in those with prior ACVD, 1.91 (1.68–2.17) in those without, 1.87 (1.63–2.16) in those with DN and 1.65 (1.46–1.87) in those without. However, the NNE for one more person to benefit (NNEB) for CVD death was lower in patients with a history of ACVD than in those without (61 vs 118). Patients with DN had lower NNEB than those without (69 vs 113). In patients with TA albumin ≥3.8 g/dL, older patients had lower NNEB, while patients with TA albumin <3.45 g/dL showed no benefit in some groups, including the elderly. Conclusions The benefit of intensive phosphate management may be pronounced in patients with a history of ACVD or DN. A comprehensive approach that considers both age and nutritional status may be necessary when managing serum phosphate levels. [ABSTRACT FROM AUTHOR] more...

Background Within the class of tyrosine kinase inhibitors (TKIs), which are used for the treatment of numerous advanced cancers, lenvatinib is associated with a higher prevalence of hypertension (HT) compared with other TKIs. In this study, we investigated the effect of lenvatinib on blood pressure (BP) and associated factors. Methods This single-centre, retrospective observational study included 25 consecutive patients treated with lenvatinib for unresectable hepatocellular carcinoma from April 2018 to December 2018 at the study institution. We assessed changes in BP using ambulatory BP monitoring, urinary sodium excretion, kidney function, use of antihypertensive agents and diuretics, and fluid retention following treatment initiation with lenvatinib. Results At 1 week after treatment initiation, the mean BP and the percentage of patients with riser pattern significantly increased compared with those at the baseline. Although there were no significant changes at 1 week, urinary sodium excretion (153.4 ± 51.7 and 112.5 ± 65.0 mEq/day at 1 and 3 weeks, respectively, P < 0.05) and estimated glomerular filtration rate significantly decreased and the number of patients with fluid retention increased at 3 weeks. Furthermore, patients with fluid retention had significantly higher BP or required more intensive BP treatment compared with those without fluid retention. Conclusions Lenvatinib might lead to HT without fluid retention soon after the initiation of treatment, subsequently leading to a reduction in urinary sodium excretion, thereby contributing to a rise in BP by fluid retention. [ABSTRACT FROM AUTHOR] more...

Background Fabry disease (FD) is a rare disorder and one of the causes of progressive renal and cardiac dysfunction. FD results from an X-linked recessive lysosomal storage disorder caused by a defect in the gene encoding lysosomal α-galactosidase A. Although accumulation of globotriaosylceramide leads to renal and cardiac manifestations, the precise mechanisms remain unclear. Coronary microvascular dysfunction may be one of the causes of cardiac complications in FD. We aimed to assess coronary flow reserve (CFR) and the effect of enzyme replacement therapy (ERT) on coronary microvascular dysfunction. Methods Four FD patients who had never received ERT were included. The serum asymmetric dimethylarginine (ADMA) level, as a marker of endothelial dysfunction, was measured. Two-dimensional guided M-mode echocardiography was performed to measure left ventricular wall mass. Adenosine-triphosphate stress transthoracic Doppler echocardiography was used to measure CFR before starting ERT and at 3, 6 and 12 months. Results All the patients tolerated ERT without any side effects. At the baseline, two patients had impaired CFR, increased left ventricular mass index (LVMI) and elevated serum ADMA levels. Twelve months after starting ERT, CFR was increased in all patients, and LVMI and serum ADMA levels decreased in two patients. Furthermore, serum ADMA levels significantly correlated with CFR (r = −0.576, P < 0.05) and LVMI (r = 0.874, P < 0.0001). Conclusions The results suggest that ERT prevented the progression of cardiac abnormalities, possibly by improving coronary microvascular dysfunction. ADMA may be a useful surrogate marker in FD. [ABSTRACT FROM AUTHOR] more...