It is classically thought that it is the amount of salt that is critical for driving acute blood pressure responses. However, recent studies suggest that blood pressure responses, at least acutely, may relate to changes in serum osmolality. Here, we test the hypothesis that acute blood pressure responses to salt can be altered by concomitant water loading. Ten healthy patients free of any disease and medication underwent 4 interventions each a week apart in which they took 300 mL of lentil soup with no salt (visit 1), lentil soup with 3 g salt (visit 2), or lentil soup with 3 g salt and 500 mL water (visit 3) or 750 mL water (visit 4). At each visit, hourly blood measurements and blood pressure measurements (baseline, 1st, 2nd, 3rd, and 4th hour) were performed and plasma osmolarity, sodium and copeptin levels were measured. Patients receiving the 3 g salt showed a 6 mOsm/L change in osmolality with a 2.5 mmol/L change in plasma sodium and 10 mm Hg rise in systolic blood pressure at 2 hours. When the same patients drank salty soup with water, the changes in plasma osmolarity, plasma sodium, and blood pressure were prevented. The ability to raise blood pressure acutely with salt appears dependent on changes in plasma osmolality rather than the amount of salt. Our findings suggest that concurrent intake of water must be considered when evaluating the role of salt in blood pressure.

Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate whether lowering UA would have an effect on mortality and cardiovascular (CV) events in patients with HF in a systematic review and meta-analysis. The primary outcome measures were all-cause mortality, CV mortality, CV events, and CV hospitalization in patients with HF. We included 11 studies in our final analysis. Overall, allopurinol treatment was associated with a significant increase in the risk for all-cause mortality (hazard ratio [HR]: 1.24, 95% confidence interval [CI]: 1.04-1.49, P = .02). The trial heterogeneity is high (heterogeneity χ ² = 37.3, I2 = 73%, P < .001). With regard to CV mortality, allopurinol treatment was associated with a 42% increased risk of CV mortality (HR: 1.42, 95% CI: 1.11-1.81, P = .005). There was a trend toward increased CV hospitalization in the same group (HR: 1.21, 95% CI: 0.95-1.53, P = .12). Uric acid-lowering treatments increase all-cause and CV mortality but did not increase CV hospitalization significantly in this study.

The most common cause of liver disease worldwide is now non-alcoholic fatty liver disease (NAFLD). NAFLD refers to a spectrum of disease ranging from steatosis to non-alcoholic steatohepatitis, causing cirrhosis, and ultimately hepatocellular carcinoma. However, the impact of NAFLD is not limited to the liver. NAFLD has extra-hepatic consequences, most notably, cardiovascular and renal disease. NAFLD and chronic kidney disease share pathogenic mechanisms including insulin resistance, lipotoxicity, inflammation and oxidative stress. Not surprisingly, there has been a recent surge in efforts to manage NAFLD in an integrated way that not only protects the liver but also delays comorbidities such as chronic kidney disease. This concept of simultaneously addressing the main disease target and comorbidities is key to improve outcomes, as recently demonstrated by clinical trials of SGLT2 inhibitors and GLP1 receptor agonists in diabetes. HIF activators, already marketed in China, also have the potential to protect both liver and kidney, as suggested by preclinical data. This review concisely discusses efforts at identifying common pathogenic pathways between NAFLD and chronic kidney disease with an emphasis on potential paradigm shifts in diagnostic workup and therapeutic management.