[Efficacy of sacubitril/valsartan in peritoneal dialysis patients with HFpEF and its effect on residual renal function].

Objective: To investigate the efficacy of sacubitril/valsartan in peritoneal dialysis (PD) patients with heart failure with preserved ejection fraction (HFpEF) and its effect on residual renal function. Methods: PD patients with HFpEF in Ningbo First Hospital from March 2018 to August 2021 were retrospectively enrolled and divided into study group with sacubitril/valsartan and control group with valsartan. The clinical baseline data before treatment and clinical indicators during follow-up (6 and 12 months after treatment) were collected and compared between the two groups, and the adverse reactions were also recorded. Results: A total of 99 patients were included in the study. There were 61 patients in the study group, including 44 males and 17 females, with a mean age of (52±13) years. Meanwhile, there were 38 patients in the control group, including 23 males and 15 females, with a mean age of (57±14) years. There was no statistically significant difference in clinical baseline data between the two groups (e.g., age, sex, body mass index, duration of dialysis) (all P>0.05). The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular end-systolic dimension (LVDs) were lower, but the left ventricular ejection fraction (LVEF) was higher in the study group than those in the control group at 6 and 12 months after treatment (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were lower than baseline values at 6 and 12 months after treatment respectively, with statistically significant differences (all P<0.05). However, there were no statistically significant differences in the decreases of SBP and DBP between the two groups at 6 and 12 months after treatment (all P>0.05). The decrease extents in residual estimated glomerular filtration rate (eGFR) [0.52 (-0.05, 1.19) vs 1.72 (0.97, 2.39) ml·min-1·(1.73 m2)-1, P<0.001]and 24-h residual urine volume [200 (-100, 300) vs 300 (137, 400) ml, P=0.018] at 12 months after treatment were lower in the study group than those in the control group. During the follow-up period, hyperkalemia occurred in 16 cases (26.2%) and 13 cases (34.2%) in the study group and the control group, and hypotension occurred in 3 cases (4.9%) and 1 case (2.6%) in the study group and the control group, respectively. There were no adverse reactions such as cough and angioneurotic edema in the two groups. Conclusions: Sacubitril/valsartan can safely and effectively improve cardiac function and lower blood pressure in PD patients with HFpEF. Compared with valsartan, sacubitril/valsartan may be more beneficial to delay the loss of residual renal function in PD patients with HFpEF.

[The urate-lowering efficacy of febuxostat and its relationship with residual renal function in peritoneal dialysis patients with hyperuricemia].

Objective: To investigate the urate-lowering efficacy of febuxostat in peritoneal dialysis (PD) patients with hyperuricemia (HUA) and its relationship with residual renal function. Methods: Patients with HUA who underwent PD in Ningbo First Hospital from January 2018 to October 2021 were enrolled and divided into experimental group and control group according to whether to use febuxostat. The clinical baseline data before treatment and clinical indicators during 1-12 months after treatment were collected in two groups, and the adverse reactions during the use of febuxostat were also recorded. The changes of serum uric acid, standard-reaching rate and residual renal function were compared between the two groups during the follow-up. Results: A total of 105 patients were included in the study. There were 55 patients in the experimental group [27 males and 28 females, with a mean age of (54.5±14.8) years] and 50 patients in the control group [32 males and 18 females, with a mean age of (53.8±15.2) years]. No statistically significant difference was detected in clinical baseline data between the two groups (all P>0.05). The serum uric acid of the experimental group [(479±77), (311±69), (286±61), (307±65), (312±57) µmol/L] and control group [(486±59), (454±71), (453±76), (463±70), (459±76) µmol/L] were lower than baseline values at 1, 3, 6 and 12 months after treatment and the differences of two groups were statistically significant (all P<0.05). The serum uric acid in experimental group was significantly lower than that of control group (P<0.05). At 1, 3, 6 and 12 months after treatment, the standard-reaching rate of serum uric acid in the experimental group was significantly higher than that of the control group (all P<0.05). The decrease of residual estimated glomerular filtration rate (eGFR) and residual renal urea clearance index (Kt/V) in the experimental group were significantly lower than those in the control group at 12 months after treatment (all P<0.05). During the follow-up, the incidence of adverse reactions in the experimental group was 9.09% (5/55). Conclusions: Febuxostat can effectively treat PD patients with hyperuricemia and has a high safety profile. Moreover, it may delay the loss of residual renal function.

Absence of the adenosine A2A receptor confers pulmonary arterial hypertension and increased pulmonary vascular remodeling in mice.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by sustained elevation of pulmonary vascular resistance resulting from endothelial and smooth muscle cell dysfunction and collagen deposition in pulmonary vascular walls. In this study, we investigated the role of the adenosine A(2A) receptor (A(2A)R) in the development of PAH by determining the effect of genetic inactivation of A(2A)Rs on pulmonary vascular remodeling in mice. METHODS AND RESULTS: We characterized hemodynamic, histological and ultrastructural changes in pulmonary vascular remodeling in A(2A)R knockout (KO) mice compared with their wild-type (WT) littermates after exposure to normoxia and hypoxic conditions. After exposure to normoxia, compared to WT mice, A(2A)R KO mice displayed: (1) increased right ventricular systolic pressures and an elevated ratio of the right ventricle over left ventricle plus septum (Fulton index), (2) increased wall area and thickness as well as enhanced smooth muscle actin immunoreactivity in pulmonary resistance vessels, (3) increased proliferating cell nuclear antigen-positive cells in pulmonary resistance vessels and (4) increased smooth muscle cells hypertrophy and collagen deposition in the adventitia of pulmonary arteriole walls as revealed by electron microscope. By contrast, histological analysis revealed no features of hypertensive nephropathy in A(2A)R KO mice and there was no significant difference in systemic blood pressure, and left ventricular masses among the 3 genotypes. Furthermore, following chronic exposure to hypoxia, A(2A)R KO mice exhibited exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels and increased cell proliferation in pulmonary resistance vessels, compared to WT littermates. Thus, genetic inactivation of A(2A)Rs selectively produced PAH and associated increased smooth muscle proliferation and collagen deposition. CONCLUSIONS: Extracellular adenosine acting at A(2A)Rs represents an important regulatory mechanism to control the development of PAH and pulmonary vascular remodeling.