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Background Metabolic acidosis accelerates chronic kidney disease (CKD) progression towards kidney failure in animal models. Clinical trials testing the effect of bicarbonate on kidney outcomes are underpowered and/or of suboptimal quality. On the other hand, observational studies testing the same hypothesis are generally based on bicarbonate measured at a single time point. Methods We studied the longitudinal relationship between repeated venous bicarbonate levels and a predefined composite renal outcome (a ≥30% estimated glomerular filtration rate reduction, dialysis or transplantation) by using group-based trajectory model (GBTM) analysis. The GBTM analysis was used to classify patients based on individual bicarbonate levels over time. The relationship between trajectory groups and renal outcomes was investigated using crude and adjusted Cox regression models. A total of 528 patients with stage 2–5 CKD were included in the analysis. Results The GBTM analysis identified four distinct trajectories of bicarbonate levels: low, moderate, moderate-high and high. During the follow-up period, 126 patients experienced the combined renal endpoint. The hazard rate of renal events decreased dose-dependently from the lowest to the highest bicarbonate trajectory. After adjusting for potential confounders, there was a 63% risk reduction for the composite renal endpoint for patients in the high trajectory category compared with those in the low trajectory category. Conclusion The study found that higher bicarbonate trajectories were associated with a lower risk of adverse renal outcomes in CKD patients. These results suggest that strategies to maintain higher bicarbonate levels may benefit patients with CKD. However, further high-quality randomised trials are needed to confirm these findings and recommend bicarbonate supplementation as a strategy to delay CKD progression. [ABSTRACT FROM AUTHOR]

Background Italy was the second country in the world, after China, to be hit by SARS-CoV-2 pandemic. Italy's experience teaches that steps to limit people's movement by imposing 'red zones' need to be put in place early by carefully identifying the cities to be included within these areas of quarantine. The assessment of the relationship between the distance from an established outbreak of SARS-CoV-2 infection with transmission-linked cases and mortality observed in other sites could provide useful information to identify the optimal radius of red zones. Methods We investigated the relationship between SARS-CoV-2 cases and the distance of each Italian province from the first outbreak of SARS-CoV-2 epidemic in Italy (the city of Lodi placed in the Lombardia region). In 38 provinces of Lombardia and neighboring regions, we performed a breakpoint analysis to identify the radius of the red zone around Lodi minimizing epidemic spread and mortality in neighboring cities. Results In all Italian provinces, a non-linear relationship was found between SARS-CoV-2 cases and distance from Lodi. In an analysis including the provinces of Lombardia and neighboring regions, SARS-CoV-2 cases and mortality increased when the distance from Lodi reduced below 92 and 140 km, respectively, and such relationships were amplified by ozone (O3) pollution. Conclusions The breakpoint analysis identifies the radius around the outbreak of Lodi minimizing the public health consequences of SARS-CoV-2 in neighboring cities. Such an approach can be useful to identify the red zones in future epidemics due to highly infective pathogens similar to SARS-CoV-2. [ABSTRACT FROM AUTHOR]