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The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], =0.192; specificity: 0.92 [95% CI, 0.85-0.97],=0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended.

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What is known and objective Previous studies based on small‐sample clinical data proved that short‐term use of hypoxia‐inducible factor prolyl hydroxylase (HIF‐PHD) inhibitors increased haemoglobin levels in anaemic patients with chronic kidney disease (CKD). However, these studies reached conflicting conclusions on iron parameters and adverse event profiles. Our meta‐analysis aimed to evaluate the long‐term efficacy and safety of HIF‐PHD inhibitors in renal anaemia. Methods Randomized controlled trials comparing treatment with HIF‐PHD inhibitors versus placebo or erythropoiesis‐stimulating agents (ESAs) were thoroughly searched in the PubMed, Embase, Cochrane Library and international clinical trial registries. Meta‐analysis was performed on main outcomes with random effects models. Results and discussion A total of 30 studies comprising 13,146 patients were included. The HIF‐PHD inhibitors used included roxadustat, daprodustat, vadadustat, molidustat, desidustat and enarodustat. HIF‐PHD inhibitors significantly increased haemoglobin levels in comparison with placebo [weighted mean difference (WMD) 1.53, 95% confidence interval (CI) 1.39 to 1.67] or ESAs (WMD 0.13, 95% CI 0.03 to 0.22). Hepcidin, ferritin and serum iron levels were decreased, while total iron binding capacity and transferrin levels were increased in the HIF‐PHD inhibitor group versus those in placebo or ESAs group. Additionally, HIF‐PHD inhibitors medication was associated with cholesterol‐lowering effects. As for safety, the risk of serious adverse events in the HIF‐PHD inhibitor group was increased in comparison with placebo group [risk ratio (RR) 1.07, 95% CI 1.01 to 1.13], but comparable to the ESAs group (RR 1.02, 95% CI 0.94 to 1.10). Compared with placebo, the agents increased the risk of diarrhoea (1.21, 1.00 to 1.47), nausea (1.46, 1.09 to 1.97), oedema peripheral (1.32, 1.01 to 1.59), hyperkalemia (1.27, 1.05 to 1.54) and hypertension (1.34, 1.02 to 1.76). Compared with ESAs, the drugs increased the risk of vomiting (1.30, 1.02 to 1.65), headache (1.27, 1.05 to 1.53) and thrombosis events (1.31, 1.05 to 1.63). What is new and conclusion HIF‐PHD inhibitors treatment effectively increased haemoglobin levels and promoted iron utilization in anaemic patients with CKD, and they were well tolerated for long‐term use. In order to avoid unfavourable effects of excessive iron consumption, it was appropriate to administer HIF‐PHD inhibitors in combination with iron supplements for long‐term treatment.

Background/Aims: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. Methods: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). Results: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. Conclusion: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria.

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The serum PEDF level is elevated in women with PCOS and is associated with IR. PEDF may play a role in the pathogenesis of IR in PCOS.

Retinol binding protein 4 (RBP4) is a novel adipocyte-secreted protein that contributes to systemic insulin resistance. Experiments in mice suggest that elevated RBP4 causes insulin resistance. In the present study, we determined serum RBP4 concentration and evaluated its association with insulin resistance in women with polycystic ovarian syndrome (PCOS); 39 PCOS women and 45 healthy control subjects were enrolled in this study. Serum RBP4, fasting plasma glucose (FPG) and fasting serum insulin (FINS) were measured in all subjects. Furthermore, oral glucose tolerance test (OGTT), Botnia clamp (an intravenous glucose tolerance test followed by an euglycemic hyperinsulinemic clamp), and measurements of sex hormones were performed in 13 control subjects and all the PCOS women. The levels of serum RBP4 were elevated in PCOS women compared with the control (11.69 +/- 6.72 versus 7.75 +/- 5.96 microg/mL, p = 0.006). RBP4 levels were positively correlated with WHR (r = 0.216, p = 0.048), and intravenous glucose tolerance test beta cell index (IVGTT-beta index) which reflected beta cell function (r = 0.309, p = 0.028), but were inversely correlated with M value during Botnia clamp, which represented insulin sensitivity (r = -0.362, p = 0.008). No correlation was found between RBP4 and age, BMI, blood pressure, FPG, FINS, 2-h postprandial glucose, 2-h postprandial insulin, free testosterone, total testosterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH). In a linear stepwise regression analysis with a model including age, BMI, WHR, free testosterone, IVGTT-beta index, and M value as independent variables, only M value showed significant correlation with serum RBP4 levels (r2 = 0.105, f = 6.640, p = 0.012). In conclusion, serum RBP4 levels are significantly increased in PCOS women and associated with insulin resistance, which indicates that RBP4 may be a contributing factor linking adipose tissue with insulin resistance in PCOS.