Estimated proximal tubule fluid phosphate concentration and renal tubular damage biomarkers in early stages of chronic kidney disease.

INTRODUCTION: An increase in proximal tubule fluid phosphate concentration is caused by increased serum fibroblast growth factor 23 (FGF23) levels, which resulted in renal tubular damage in a mouse model of chronic kidney disease (CKD). However, few human studies have supported this concept. This study aimed to explore the association among estimated proximal tubule fluid phosphate concentration (ePTFp), serum FGF23 levels, and renal tubular damage biomarkers in middle-aged and older populations with mild decline in renal function. METHODS: This cross-sectional study included 218 participants aged ≥45 with CKD stages G2-G4. Anthropometric measurements, blood tests, spot urine biomarkers, renal ultrasonography, cardiovascular assessment, smoking status, and medication usage were obtained in the morning in fasted states. The ePTFp was calculated using serum creatinine, urine phosphate, and creatinine concentrations. Urinary ß2-microglobulin and liver-type fatty acid-binding protein (L-FABP) levels were evaluated to assess renal tubular damage. RESULTS: ePTFp, serum FGF23, urinary ß2-microglobulin, and urinary L-FABP levels increased with CKD stage progression (stages G2, G3, and G4). However, serum and urine phosphate concentrations were comparable across the CKD stages. Univariate analysis revealed a stronger correlation of ePTFp with serum FGF23, urinary ß2-microglobulin, and urinary L-FABP levels than with the corresponding serum and urine phosphate concentrations. Multivariate analyses demonstrated that increased ePTFp was independently associated with elevated serum FGF23 and urinary ß2-microglobulin levels, even after adjusting for potential covariates, including the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. CONCLUSIONS: Our results are consistent with the concept in mouse model and suggest that increased ePTFp are associated with increased serum FGF23 levels and renal tubular damage during the early stages of CKD.

Systemic Capillary Responses to Acute Exercise in Hypertensive Seniors: Insights from a Single-Center Pilot Study.

Objective: The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. DESIGN: This study was a single- center pilot trial. SETTING: The study took place in the Faculty of Health, Tsukuba University of Technology, Japan. PARTICIPANTS: Hypertensive community-dwelling elderly people took part in the study. INTERVENTION: Microcirculation was observed before and 1 min after an arm-curl exercise by means of capillary microscopy of the non-exercised limb. Additionally, we examined other health-related indicators. Methods: We measured the acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters. Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3 ± 6.7 to 2.7 ± 0.2 log µm/s (p < 0.01), and the capillary density changed from 0.8 ± 0.2 to 0.9 ± 0.1 log/mm (p < 0.01), which included a significant increase in the non-exercising limb. Significant correlations were observed between the nailfold capillary diameter and body fat mass, the capillary diameter and physical activity, and the capillary density and bone mineral density. Conclusions: The acute effects of exercise on high-risk elderly individuals can be safe, and even 1 of min exercise can potentially improve their nailfold capillary function, despite the brief time, compared to no exercise. The results indicate that capillaries have an impact on the function of the whole body. Thus, they may be a useful diagnostic tool for assessing nailfold capillaries.

CRP and soluble CTLA4 are determinants of anti-PD1 resistance in gastrointestinal cancer.

Targeting immune inhibitory checkpoint (IC) pathways have attracted great attention as a promising strategy for treating gastrointestinal (GI) cancer. However, the therapeutic efficacy is low in most cases, and little progress has been made in establishing biomarkers that predict the possible responses, and combination regimens that enhance the therapeutic efficacy. As a predictive biomarker, soluble forms of IC molecules have been recently highlighted. However, little is known about which IC molecules is most critically associated with the treatment resistance, and also about the biological and immunological roles of the IC molecules in GI cancer. In this study, we analyzed sera obtained from advanced gastric cancer patients before and one month after treatment with anti-PD1 nivolumab for soluble IC molecules by ELISA. We found that decrease of soluble CTLA4 (sCTLA4) at posttreatment were significantly associated with a better prognosis, and combination with low level of CRP at posttreatment more clearly defined anti-PD1 responders with long-term survival. Indeed, in the in vitro setting, CRP stimulation upregulated CTLA4 expression in tumor cells followed by generation of sCTLA4 that suppressed CTL induction, and simultaneously conferred high self-renewal and invasive abilities on the tumor cells accompanied by increase of EMT-related gene expressions. In the in vivo setting, CRP injection elevated sCTLA4 level in sera of mouse tumor metastasis models, leading to failure of anti-PD1 therapy. However, treatment with anti-CTLA4 mAb or a PPARγ agonist that can reduce in vivo CRP successfully elicited anti-tumor efficacy in the anti-PD1 resistant models. These suggest that targeting CRP and sCTLA4 may be a promising strategy for improving clinical outcomes in the treatments, including anti-PD1 therapy, of GI cancer.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study.

OBJECTIVE: The Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease and CVD. This study aimed to measure health-related quality of life in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured quality of life (QOL) scores. METHODS: The EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the Frontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in Japan study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. RESULTS: The response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880-0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.826-1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767-0.881), and the median was 0.828 (IQR, 0.755-1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811-0.943), and the median was 1.000 (IQR, 0.723-1.000). The mean QOL score in participants with 50% decline in estimated glomerular filtration was 0.893 (95% CI, 0.860-0.926), and the median was 0.889 (IQR, 0.825-1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere-Terpstra test for trend (P = .002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. CONCLUSION: We suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of end-stage kidney disease/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future health-related quality of life in patients with CKD.

Association of Lower Extremity Muscle Strength and Function with Renal Resistive Index in Individuals with and without Chronic Kidney Disease.

Age-related loss of lower extremity muscle strength is pronounced in individuals with chronic kidney disease (CKD). In contrast, an increase in intrarenal flow pulsatility results in initial age-related changes in renal hemodynamics, leading to the development of CKD. To date, it remains unclear whether lower extremity muscle strength determines elevated renal flow pulsatility. This study aimed to determine the association of lower extremity muscle strength and function with intrarenal hemodynamics in individuals with and without CKD. One hundred seventy-six individuals without CKD (aged 63 ± 9 years) and 101 individuals with CKD (aged 66 ± 8 years) were included in this study. Using Doppler ultrasound, the renal resistive index (RI) was measured as a parameter of renal hemodynamics. Knee extensor muscle strength (KES), gait speed (GS), and the 30 s chair stand test (30s-CST) were used to measure lower extremity muscle strength and function. Multivariate analyses showed that GS and 30s-CST scores were independent determinants of renal RI, whereas the KES score was not associated with renal RI in individuals with and without CKD. In the two-way analysis of covariance, renal RI was the highest in individuals with CKD who had lower KES, GS, and 30s-CST scores. Reduced lower extremity muscle strength and function are independent determinants of elevated renal flow pulsatility in individuals with and without CKD.

IL25+ macrophages are a key determinant of treatment resistance of IL17RB+ breast cancer.

Recurrence and metastasis are resistant to multimodal treatments, and are the major causes of death in breast cancer. Accumulating evidence suggests that the IL17RB signaling pathway plays a key role in progression and metastasis of breast cancer. Clinical significance of the IL17RB positivity in tumor tissues has been also reported as a poor prognostic factor in breast cancer. However, the molecular mechanisms underlying the poor prognosis of patients with IL17RB+ breast cancer, particularly the immunological aspects, remain to be fully elucidated, and elimination of the IL17RB+ tumors has not been practically achieved in clinical settings. In this study, we identified a distinct molecular mechanism underlying the intractability of the IL17RB+ tumors through tumor biological and immunological investigation using mouse and human breast cancer cells transduced with il17rb gene. IL17RB overexpression in tumor cells confers cancer stemness, including high invasive and self-renewal abilities, and high resistance to CDK4/6 inhibitors that have been considered as a promising agent for treating breast cancer despite the limited efficacy. In the mice implanted with the IL17RB+ tumors, IL25+ macrophages (Møs) are expanded locally in tumor tissues and systemically in spleen, and promote the IL17RB+ tumor progression directly by intensifying the tumor functions, and indirectly via impairment of anti-tumor effector CTLs and NK cells utilizing the secreted IL25. Blocking IL25 with the specific mAb, however, interferes the adverse events, and successfully elicits significant anti-tumor efficacy in combination with CDK4/6 inhibitors providing better survival in murine mammary tumor models. These results suggest that the IL25+ Mø is a key determinant of building the solid treatment resistance of the IL17RB+ breast cancer. Targeting the IL17RB-IL25 axis may be a promising strategy to improve clinical outcomes in the treatment of breast cancer patients, particularly with IL17RB+ tumors.

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations.

Inappropriate activation of intrarenal renin-angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Association between trunk flexibility and renal flow pulsatility in middle-aged and older adults.

BACKGROUND: Recent clinical studies have indicated that poor trunk flexibility is associated with arterial stiffness in the aged. Arterial stiffness leads to elevated renal flow pulsatility, which accelerates age-related renal dysfunction and damages. However, data indicating the potential link between flexibility fitness and renal flow pulsatility are lacking. This study examined the cross-sectional association between trunk flexibility and renal flow pulsatility in middle-aged and older adults. METHODS: A total of 175 middle-aged and older adults (aged 63 ± 9 years) were included in this study. Sit-and-reach tests (SRT) were performed to assess their trunk flexibility. Using a Doppler ultrasound, renal pulsatility index (PI) and resistive index (RI) were measured as parameters of renal flow pulsatility. RESULTS: The study found that, in middle-aged and older adults, the SRT score was an independent determinant of renal PI (ß = -0.134, P = 0.027) and RI (ß = -0.135, P = 0.027). In the one-way analysis of covariance (ANCOVA), the renal PI and RI in the older group with a lower SRT score were found to be significantly higher than those in the middle-aged group. CONCLUSIONS: Trunk flexibility is an independent determinant of renal flow pulsatility in middle-aged and older adults.

Association between the intake of plant and animal proteins and the serum fibroblast growth factor-23 level in patients with chronic kidney disease analyzed by the isocaloric substitution model.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by the bone in response to dietary phosphate intake. Since the phosphate content in the diet correlates with the protein content, both plant- and animal-based protein intake can increase the serum FGF23 level. However, a higher percentage of energy from plant protein than from animal protein is associated with a lower serum FGF23 level in patients with chronic kidney disease (CKD) in the United States. Since dietary habits differ between Asian and Western populations, we performed a cross-sectional study to determine the association between the percentages of energy from plant and animal proteins and the serum FGF23 level in Japanese CKD patients. In 107 non-dialysis CKD patients (age: 66 ± 9 years; estimated glomerular filtration rate: 56 ± 21 mL/min/1.73 m2), the percentages of energy from plant and animal proteins were assessed using a food frequency questionnaire based on food groups. Venous blood samples were used to measure the serum FGF23, phosphate, 1,25-dihydroxyvitamin D, and intact parathyroid hormone levels. The percentages of energy from plant and animal proteins showed a negative and positive association, respectively, with the serum FGF23 level. Furthermore, isocaloric substitution modeling showed that replacing animal protein with plant protein was associated with a low serum FGF23 level. Our findings suggest that encouraging diets with high plant protein level may prevent an increase in the serum FGF23 level in Japanese CKD patients.

[Comparison between Single and Three Times Pre-operative Administration of Amoxicillin in the Prophylactic Effects for Surgical Site Infections in Japanese Patients with Mandibular Third Molars Extraction].

Although the dosage of oral antibiotics (OA) for the mandibular third molar extraction (MTME) varies among the administration periods according to the current guideline, our previous reports suggested that it might be possible to further shorten the administration period without increasing the incidence of surgical site infection (SSI). In the present study, we retrospectively evaluated the relationship between the incidence of SSI and the administration period of OA in patients who underwent the MTME in our hospital. This retrospective cohort study included 348 patients who underwent the MTME in our dental outpatient clinic from June 2020 to March 2022. The administrated antibiotic was amoxicillin (AMPC) in all patients. Patients were divided into two groups based on the administration period of AMPC single and three times before the surgery. The following information was collected: (1) patient factors (age, gender, body mass index, diagnosis, mandibular third molar status); (2) surgical factors (operation time, presence/absence of wound closure, presence/absence of hemostat, experience of surgeons); (3) relationship between administration period of OA and SSI occurrence; and (4) details of SSI. There were 217 cases in the single group and 131 cases in the three times group. The incidence of SSI was 1.1% (4/348), with 1.4% (3/217) in the single group and 0.8% (1/131) in the three times group; there was no significant difference between the two groups. Our result suggests that single administration of AMPC before the MTME would be sufficient for the prevention of SSI in Japanese patients without risk factors.

Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer.

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the interest in development of the immune checkpoint blocking antibody inhibitors (ICIs). Abnormality of myeloid cells must impact on the entire host, including immune responses, stromagenesis, and cancer cells, leading to refractory cancer. This implies that elimination and reprogramming of the tumor-supportive myeloid villains may be a breakthrough to efficiently induce potent anti-tumor immunity in cancer patients. In this review, we provide an overview of current situation of the IC-blocking therapy of gastrointestinal cancer, including gastric, colorectal, and esophageal cancers. Also, we highlight the possible oncoimmunological components involved in the mechanisms underlying the resistance to the ICI therapy, particularly focusing on myeloid cells, including unique subsets expressing IC molecules. A deeper understanding of the molecular and cellular determinants may facilitate its practical implementation of targeting myeloid villains, and improve the clinical outcomes in the ICI therapy of gastrointestinal cancer.

The efficacy and safety of mizoribine for maintenance therapy in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis: the usefulness of serum mizoribine monitoring.

BACKGROUND: The life prognosis of elderly patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies-associated vasculitis (MPO-AAV) has been improved by reducing the corticosteroid or cyclophosphamide dose to avoid opportunistic infection. However, many elderly MPO-AAV patients experience recurrence and renal death. An effective and safer maintenance treatment method is necessary to improve the renal prognosis of MPO-AAV. METHODS: Patients with MPO-AAV who reached complete or incomplete remission after induction therapy were prospectively and randomly divided into mizoribine (MZR; n = 25) and control (n = 28) groups. The primary endpoint was relapse of MPO-AAV. The patients' serum MZR concentration was measured before (C0) and 3 h after taking the MZR. The maximum drug concentration (Cmax) and the serum MZR concentration curves were determined using population pharmacokinetics parameters. We also assessed the relationship between the MZR concentrations and adverse events. The observation period was 12 months. RESULTS: Fifty-eight MPO-AAV patients from 16 hospitals in Japan were enrolled. Ten patients relapsed (MZR group, n = 6; control group, n = 4; a nonsignificant between-group difference). Changes in the serum MZR concentration could be estimated for 22 of the 25 MZR-treated patients: 2 of the 11 patients who reached a Cmax of 3 µg/mL relapsed, whereas 4 of the 11 patients who did not reach this Cmax relapsed. The treatment of one patient with C0 > 1 µg/mL was discontinued due to adverse events. No serious adverse events occurred. CONCLUSION: There was no significant difference in the recurrence rate of MPO-AAV between treatment with versus without MZR.

Cerebral and renal hemodynamics: similarities, differences, and associations with chronic kidney disease and aortic hemodynamics.

Elevated arterial pulsatility is a common risk factor for cerebrovascular disease and chronic kidney disease (CKD), which suggests that the brain and kidneys may have similar hemodynamic profiles. The objectives of this study were twofold: 1) to compare and contrast the cerebral and renal blood flow parameters in adults without CKD (hereafter, non-CKD adults) and CKD patients and 2) to determine the common predictor(s) of cerebral and renal hemodynamics among pressure pulsatility and several cardiovascular risk factors. In 110 non-CKD adults and 66 CKD patients, cerebral and renal blood flow velocity (BFV) were measured by transcranial Doppler and Duplex ultrasonography, respectively. Pulsatile hemodynamics were assessed by the pulsatility (PI) and resistive (RI) indices. Aortic pulse pressure was measured by tonometry. Compared with non-CKD adults, CKD patients showed greater pulsatility of the BFV (i.e., systolic minus diastolic BFV), PI, and RI in the kidneys but not the brain. However, the cerebral and renal PI and RI values were strongly correlated in both non-CKD adults (both PI and RI values: rs = 0.695) and CKD patients (both PI and RI values: rs = 0.640) (all P < 0.001). Multiple linear regression analysis further demonstrated that the cerebral and renal PI and RI associations remained significant after adjustment for potential covariates (e.g., age, sex, the presence of CKD). The aortic pulse pressure was a significant predictor for both cerebral and renal PI and RI values. Collectively, our findings suggest that CKD patients have higher renal flow pulsatility, which is strongly and independently associated with cerebral flow pulsatility and aortic hemodynamics.

Blocking FSTL1 boosts NK immunity in treatment of osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. Many patients develop relapse and metastasis after treatments, and more effective treatments are needed for improving the clinical outcome. FSTL1 overexpression has been reported in murine and human OS, while the functional roles of FSTL1 remain unclear. Here, we elucidated tumor biological and immunological mechanisms underlying the refractory OS using mouse and human OS cell lines, mouse OS models, and clinical specimens. FSTL1 knockout in OS cells significantly suppressed cellular functions, including proliferation, invasion, sphere colony formation, and ALCAM expression. The FSTL1-ablated tumor cells were completely rejected due to generation of potent NK cells in the in vivo setting. Indeed, FSTL1 stimulation suppressed NK activity partly via apoptosis induction, but blocking FSTL1 or CD6, a receptor for ALCAM, significantly restored NK activity. Anti-FSTL1 therapy significantly suppressed tumor growth and metastasis in mouse OS models, and synergized with anti-CD6 therapy in providing significantly better prognosis. These suggest that blocking FSTL1 is a promising strategy for successfully treating OS. This study demonstrates a rationale of targeting the FSTL1-ALCAM axis in the treatment of OS in clinical settings.

Sedentary behavior is associated with reduced cardiovagal baroreflex sensitivity in healthy adults.

Sedentary behavior is an established risk factor for cardiovascular disease; however, it remains unclear whether sedentary behavior is associated with the deterioration of arterial blood pressure regulation. The purpose of this study was to determine the association between the time spent in sedentary behavior and cardiovagal baroreflex sensitivity (cBRS) in healthy adults. We investigated the cross-sectional relationship between sedentary time and cBRS in 179 adults aged 22-81 years. Sedentary time was objectively measured using a triaxial accelerometer. cBRS was evaluated by the transfer function gain of beat-by-beat changes in systolic blood pressure and the R-R interval during 5 min of spontaneous resting. Glycemic, lipidemic, and vascular risk factors were measured as potential covariates of cBRS and sedentary behavior. Men had a longer sedentary time and lower cBRS than women (p = 0.001). In a simple correlation analysis, older age was negatively associated with cBRS and positively associated with sedentary time, but sedentary time was not correlated with cBRS. However, after adjustment for age and sex, a longer sedentary time was associated with a lower cBRS. Multiple linear regression analysis showed that sedentary time was independently associated with lower cBRS with adjustment for covariates (ß = -0.325, p = 0.002). A significant association was also confirmed when the analysis was performed separately in the younger and older groups. This finding suggests that high sedentary behavior may have an adverse effect on arterial blood pressure regulation.

Association of circulating calciprotein particle levels with skeletal muscle mass and strength in middle-aged and older adults.

Calciprotein particles (CPPs) are tiny mineral-protein aggregates consisting of calcium-phosphate and fetuin-A. Recent studies have suggested that CPPs may contribute to the pathogenesis of chronic inflammation and arteriosclerosis. Reduced skeletal muscle mass and strength reportedly contribute independently to increased serum phosphate levels. This finding suggests that reduced skeletal muscle mass and strength can endogenously induce an increase in circulating CPP levels. Therefore, we investigated the potential association between circulating CPP levels and skeletal muscle mass and strength in middle-aged and older adults. One hundred eighty-two middle-aged and older adults (age, 46-83 years) were included in this cross-sectional study (UMIN000034741). Circulating CPP levels were measured using the gel filtration method. Appendicular skeletal muscle mass was assessed using multifrequency bioelectrical impedance analysis with a tetrapolar eight-point tactile electrode system. The skeletal muscle mass index was calculated from appendicular skeletal muscle mass and height. Handgrip and knee extension strengths were used as measures of skeletal muscle strength. The skeletal muscle mass index was negatively correlated with circulating CPP levels (r = -0.31; P < 0.05). This association remained significant after adjustment for potential covariates (ß = -0.34; P < 0.05). In contrast, skeletal muscle strength, represented by handgrip strength and knee extension strength, was not significantly associated with circulating CPP levels. In middle-aged and older adults, a lower skeletal muscle mass index was independently associated with higher circulating CPP levels. The present results suggest that maintaining skeletal muscle mass may prevent an increase in circulating CPP levels.