Atrial fibrillation (AF), a common arrhythmia in critically ill patients, significantly affects prognosis. While phosphate disturbances are strongly associated with cardiovascular risks, the impact of serum phosphate on critically ill AF patients' prognosis remains uncertain.

Utilizing data from the MIMIC-IV database, we retrospectively analyzed 11,744 critically ill AF patients. The primary outcome was 30-day all-cause mortality, with secondary outcomes at 90 days and 1 year. Cox regression models quantified the association between serum phosphate and mortality. Nonlinear associations were evaluated using restricted cubic splines (RCS), with inflection points further characterized through segmented Cox proportional hazards model.

Mortality rates at 30 days, 90 days, and 1 year were 12.7 %, 14.4 %, and 15.8 %, respectively. Kaplan-Meier analysis showed higher mortality in patients with high phosphate levels. Adjusted Cox regression demonstrated that hyperphosphatemia independently predicted increased mortality at 30 days (HR: 1.55, 95 % CI: 1.36-1.78, p < 0.001), 90 days (HR: 1.55, 95 % CI: 1.37-1.76, p < 0.001), and 1 year (HR: 1.57, 95 % CI: 1.39-1.77, p < 0.001). RCS and two-piece Cox regression revealed a U-shaped nonlinear relationship between serum phosphate and mortality, with risk decreasing below a threshold and increasing above it. Similar patterns were observed across all time points.

Our findings demonstrated a U-shaped relationship between serum phosphate levels and mortality in critically ill AF patients, highlighting the importance of maintaining optimal phosphate levels in managing this population.

Serum phosphate levels have been reported to be linked to the prognosis in critically ill patients. The purpose of this study was to analyze the impact of the trajectory of changes in serum phosphate levels on the short-term mortality risk in patients with sepsis.

This retrospective cohort study used data on patients with sepsis from the 2008-2019 Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Serum phosphate level trajectories were constructed using a latent growth mixture modeling (LGMM) based on four measurements of serum phosphate at six-hour intervals within 24 h of admission to the intensive care unit (ICU). The relationship between serum phosphate levels at ICU admission and serum phosphate level trajectories and the risk of 28-day mortality in patients with sepsis was analyzed using Cox regression models, and hazard ratio (HR) and 95% confidence interval (CI) were calculated.

Of these 1,703 patients with sepsis included, 566 (33.24%) died within 28 days. The median serum phosphate levels of the patients were 4.10 (3.00, 5.50) mg/dL. Four serum phosphate level trajectories were classified: normal-level-steady trend (trajectory 1), high-level-steady trend (trajectory 2), high-level-decreasing trend (trajectory 3), and high-level-increasing trend (trajectory 4). High serum phosphate levels at admission were associated with a higher risk of 28-day mortality (HR = 1.05, 95%CI: 1.01-1.09) in patients with sepsis. For trajectories, trajectory 2 (HR = 1.27, 95%CI: 1.05-1.54) related to an increased risk of 28-day mortality compared with trajectory 1, whereas trajectory 4 (HR = 1.69, 95%CI: 0.99-2.91, P = 0.056) may be related. There was no significant difference in 28-day mortality between patients on trajectory 3 and trajectory 1 (P = 0.280). Subgroup analyses demonstrated that patients with trajectory 2 were linked to a higher risk of 28-day mortality in different population subgroups (P < 0.05).

Stable trajectories of high serum phosphate levels are an important risk factor for short-term mortality in patients with sepsis.

Essential element concentrations in biological samples may be related to the pathogenesis of various diseases. Previous studies have reported that serum iron (Fe), zinc (Zn), and copper (Cu) were related to acute myocardial infarction (AMI). However, the differences in element concentrations between AMI and other cardiac disease has not been investigated. In this study, differences in plasma Fe, magnesium (Mg), Zn, Cu, calcium (Ca), inorganic phosphorus (P), and cardiac troponin T (TnT) levels in heart disease patients (AMI, angina, heart failure, and chest pain) were investigated to explore potential markers of AMI. Fe, Mg, Zn, and Cu concentrations were assayed by using a Metallo Assay kit; Ca and inorganic P were determined by using an automatic biochemical analyzer; and cardiac TnT levels were assayed by using enzyme-linked immunosorbent assay. Plasma TnT levels were higher in AMI than in other heart diseases and were negatively correlated with Cu and Ca. Fe, Cu, and inorganic P levels were within the normal range, while Mg and Ca levels were lower, and Zn levels were higher than the normal range in heart disease patients. Except Mg, no significant differences in element levels were observed among heart diseases: Mg levels were significantly higher in AMI than in heart failure. These results suggest that lower Cu and Ca levels and a higher Mg level compared with other heart diseases may be a marker of AMI.

Chronic kidney disease (CKD) is associated with systemic phosphate elevations, called hyperphosphatemia. Translational studies have shown that hyperphosphatemia contributes to CKD-associated inflammation and injury in various tissues, including the kidney, heart, liver, and parathyroid gland. Mechanisms underlying pathologic actions of elevated phosphate on cells are not well understood but seem to involve uptake of phosphate through sodium phosphate cotransporters and phosphate-induced signaling via FGFR1 (fibroblast growth factor receptor 1). Clinical studies indicate patients with CKD are more likely to develop inflammatory and restrictive lung diseases, such as fibrotic interstitial lung diseases, and here we aimed to determine whether hyperphosphatemia can cause lung injury. We found that a mouse model of CKD and hyperphosphatemia, induced by an adenine-rich diet, develops lung fibrosis and inflammation. Elevation of systemic phosphate concentration by administration of a high-phosphate diet in a mouse model of primary lung inflammation and fibrosis, induced by bleomycin, exacerbated lung injury in the absence of kidney damage. Our in vitro studies identified increases of proinflammatory cytokines in human lung fibroblasts exposed to phosphate elevations. Phosphate activated ERK 1/2 (extracellular signal-related kinase 1/2) and PKB/AKT (protein kinase B) signaling, and pharmacological inhibition of ERK, AKT, FGFR1, or sodium phosphate cotransporters prevented phosphate-induced proinflammatory cytokine upregulation. In addition, inhibition of FGFR1 or sodium phosphate cotransporters decreased the phosphate-induced activation of ERK and AKT. Our study suggests that phosphate can directly target lung fibroblasts and induce an inflammatory response and that hyperphosphatemia in CKD and non-CKD models contributes to lung injury. Phosphate-lowering strategies might protect from CKD-associated lung injury.

This study aimed to investigate the relationship between serum phosphate levels, changes in serum phosphate levels, and 28-day mortality in patients with septic shock. In this retrospective study, data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients were divided into three groups according to the tertiles of serum phosphate levels. Kaplan-Meier curves and log-rank test analyses were used for survival analysis. Multivariate logistic regression, and restricted cubic spline (RCS) curve were used to explore the association between serum phosphate, delta serum phosphate levels and 28-day mortality. In total, 3296 patients with septic shock were included in the study, and the 28-day mortality was 30.0%. Serum phosphate levels were significantly higher in the non-survivor group than in the survivor group. The Kaplan-Meier curves showed significant differences among the three groups. Multivariate logistic regression analysis and the RCS curve showed that serum phosphate levels were independently and positively associated with the 28-day mortality of septic shock. Non-survivors had higher delta serum phosphate levels than survivors. Survival analysis showed that patients with higher delta serum phosphate levels had higher 28-day mortality. A non-linear relationship was detected between delta serum phosphate and 28-day mortality with a point of inflection at - 0.3 mg/dL. Serum phosphate levels were positively and independently associated with 28-day mortality in septic shock. Delta serum phosphate level was a high-risk factor for patients with septic shock.

Breast cancer is associated with phosphate toxicity, the toxic effect from dysregulated phosphate metabolism that can stimulate tumorigenesis. Phosphate toxicity and dysregulated phosphate metabolism are also associated with bone mineral abnormalities, including excessive bone mineral loss and deposition. Based on shared associations with dysregulated phosphate metabolism and phosphate toxicity, a hypothesis proposed in the present mixed methods-grounded theory study posits that middle-aged women with incidence of breast cancer had a greater magnitude of changes in bone mineral density over time compared with women who remained cancer-free. To test this hypothesis, a mixed-effects model was used to analyze the associations of breast cancer incidence with spinal bone mineral density changes in the U.S. Study of Women's Health Across the Nation. Compared with women in the cohort who remained cancer-free, women who self-reported breast cancer had higher bone mineral density at baseline, but had more rapid losses in bone mineral density during follow-up visits. These findings agree with the hypothesis that a greater magnitude of changes in bone mineral density over time is associated with breast cancer in a cohort of middle-aged women. The findings also have implications for studies investigating dysregulated phosphate metabolism and phosphate toxicity as causative factors of bone metastasis in metastatic breast cancer. Additionally, the authors previously found increased breast cancer risk associated with high dietary phosphate intake in the same cohort of middle-aged women, and more studies should investigate a low-phosphorus diet to reduce bone mineral abnormalities and tumorigenesis in breast cancer patients.

The consumption of ultra-processed food (UPF) keeps rising, and at the same time, an increasing number of epidemiological studies are linking high rates of consumption of UPF with serious health outcomes, such as cardiovascular disease, in the general population. Many potential mechanisms, either in isolation or in combination, can explain the negative effects of UPF. In this review, we have addressed the potential role of inorganic phosphate additives, commonly added to a wide variety of foods, as factors contributing to the negative effects of UPF on cardiorenal disease. Inorganic phosphates are rapidly and efficiently absorbed, and elevated serum phosphate can lead to negative cardiorenal effects, either directly through tissue/vessel calcification or indirectly through the release of mineral-regulating hormones, parathyroid hormone, and fibroblast growth factor-23. An association between serum phosphate and cardiovascular and bone disease among patients with chronic kidney disease is well-accepted by nephrologists. Epidemiological studies have demonstrated an association between serum phosphate and dietary phosphate intake and mortality, even in the general American population. The magnitude of the role of inorganic phosphate additives in these associations remains to be determined, and the initial step should be to determine precise estimates of population exposure to inorganic phosphate additives in the food supply.

Premature aging causes morphological and functional changes in the kidney, leading to chronic kidney disease (CKD). CKD is a global public health issue with far-reaching consequences, including cardio-vascular complications, increased frailty, shortened lifespan and a heightened risk of kidney failure. Dialysis or transplantation are lifesaving therapies, but they can also be debilitating. Currently, no cure is available for CKD, despite ongoing efforts to identify clinical biomarkers of premature renal aging and molecular pathways of disease progression. Kidney proximal tubular epithelial cells (PTECs) have high energy demand, and disruption of their energy homeostasis has been linked to the progression of kidney disease. Consequently, metabolic reprogramming of PTECs is gaining interest as a therapeutic tool. Preclinical and clinical evidence is emerging that NAD+ homeostasis, crucial for PTECs' oxidative metabolism, is impaired in CKD, and administration of dietary NAD+ precursors could have a prophylactic role against age-related kidney disease. This review describes the biology of NAD+ in the kidney, including its precursors and cellular roles, and discusses the importance of NAD+ homeostasis for renal health. Furthermore, we provide a comprehensive summary of preclinical and clinical studies aimed at increasing NAD+ levels in premature renal aging and CKD.

This study aimed to evaluate the possible relationship between serum phosphate and short-term outcomes in sepsis.

This was a retrospective study. Sepsis patients in MIMIC-IV database were included. Based on the quartiles of serum phosphate, all sepsis patients were divided into four groups. Univariable and multivariable regression analyses were constructed for discussing the relationship between different parameters and 30-day mortality in sepsis. A generalized additive model was performed for exploring the association of serum phosphate with 30-day mortality.

6251 sepsis patients including 4368 survivors and 1883 non-survivors were included. A significant relationship between serum phosphate and 30-day mortality was found after adjusting for all potential confounders (OR = 1.19, 95%CI:1.13-1.26, P < 0.0001). The relationship was non-linear with an inflection point of 6.8 mg/dl. On the left side of the inflection point (≤6.8 mg/dl, n = 5911 (94.56%)), the OR was 1.24 (95%CI: 1.17-1.31, P < 0.0001). On the right side of the inflection point (>6.8 mg/dl, n = 340 (5.44%)), the OR was 0.94 (95%CI:0.78-1.13, P = 0.5038).

A non-linear positive relationship was found between serum phosphate and 30-day mortality in sepsis. Serum phosphate was associated with mortality in sepsis. Our results could be used for screening out those sepsis patients with higher risk of worse outcomes.

Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ecosystems and humans consuming alligator meat have been studied for over three decades. Now that alligators are being recreationally hunted and consumed across their range, it is especially important to monitor toxic contaminant levels to best understand possible adverse impacts of exposures on alligator populations and human health. In this study, we determined blood Hg concentrations in American alligators from an urbanized site in Wilmington, NC, a nearby site at Lake Waccamaw, NC, and a site on the St Johns River in Florida. Median blood total Hg (tHg) concentrations were particularly high at Lake Waccamaw (526 ng/g, range 152-946 ng/g), resulting in median muscle concentrations (0.48 mg/kg, range 0.13-0.88 mg/kg) well above US EPA screening values for fish consumption. Median concentrations at the Wilmington site (69 ng/g, range 22-336 ng/g) were generally low, and Hg concentrations from the St Johns River site (143 ng/g, range 54-244 ng/g) were comparable to those reported in previous studies. Analysis of relationships between tHg concentrations and a panel of blood chemistry biomarkers found only modest concentration-dependent impact on biomarkers of renal function. The results of this study reveal that local environmental factors greatly impact Hg bioaccumulation in alligators, findings that reaffirm local contaminant biomonitoring in alligator populations will be critical for affective management and determination of guidelines for safe consumption of harvested alligators.

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production.