Publications by authors named "Kuro-o M"
Background And Objective: In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.
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- - The study investigates the levels of soluble αKlotho, a protein linked to aging, found in blood, particularly focusing on its origin from the kidneys.
- - Blood samples were taken from patients during adrenal venous catheterization to measure αKlotho levels in different sections of the inferior vena cava.
- - Results showed higher αKlotho concentrations above the kidneys (suprarenal) compared to below (infrarenal), indicating that the kidneys significantly contribute to αKlotho levels in the bloodstream.
Article Synopsis
- Hemodialysis patients respond differently to vaccines, exhibiting less antibody response and varied vaccine dosing, prompting a study on their antibody glycosylation profiles following vaccination and infection with SARS-CoV-2.
- The research involved analyzing plasma samples from 112 hemodialysis patients across four groups: control, infected, vaccinated, and those infected post-vaccination, along with examining samples before and after a booster dose.
- Results showed both vaccination and infection resulted in reduced fucosylation of IgG1 (indicating inflammation), while vaccination increased anti-inflammatory markers like galactosylation, highlighting the need to consider antibody glycosylation when assessing vaccine efficacy and development.
Article Synopsis
- Recent studies have shown that higher levels of blood calciprotein particles (CPP) are linked to vascular calcification and cardiovascular issues in patients on hemodialysis, despite varying levels among individuals with similar phosphorus levels.
- This study examined whether the ratio of serum CPP to serum phosphate (CPP/Pi ratio) could better predict cardiovascular events compared to traditional calcification tests (T) in 174 new hemodialysis patients.
- Results indicated that the CPP/Pi ratio was a significant independent predictor of major heart and brain-related events, whereas traditional calcification propensity tests did not show a similar association.
Article Synopsis
- The study investigates the link between elevated phosphate concentrations in the proximal tubule, serum FGF23 levels, and kidney damage in middle-aged individuals with mild chronic kidney disease (CKD).
- Involving 218 participants aged 45 and older, researchers measured various health indicators and found that as CKD progresses, levels of ePTFp, serum FGF23, and markers of kidney damage all increased, although phosphate concentrations remained stable.
- The findings suggest that higher ePTFp correlates strongly with increased serum FGF23 and kidney damage biomarkers, supporting previous mouse studies and indicating potential mechanisms of kidney injury in humans with CKD.
Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by osteocytes in response to dietary phosphate intake. An increase in FGF23 level is an indicator of excess phosphate intake relative to the residual nephron number. Therefore, avoiding excessive phosphate intake and inhibiting the elevation of serum FGF23 levels are important to preserve the number of functional nephrons.
View Article and Find Full Text PDFLevels of circulating soluble thrombomodulin (sTM), an anticoagulant factor, are associated with the severity and progression of arteriosclerotic diseases. However, the role of elevated sTM levels remains to be clarified in patients on dialysis. As the calcification propensity time T50 is a novel marker of arterial calcification, we aimed to determine the association between sTM and T50 in patients on hemodialysis (HD).
View Article and Find Full Text PDFBackground And Hypothesis: Extended-hours haemodialysis (HD) is associated with better clinical outcomes than conventional HD. We investigated whether extended-hours HD and conventional HD have varying effects on blood levels of calciprotein particles (CPPs) and phosphorus, which have been identified as major pathogenic molecules for vascular calcification.
Methods: Patients who underwent conventional or extended in-centre daytime HD between January and March 2020 were included.
Overexpression of the longevity gene Klotho prolongs lifespan, while its knockout shortens lifespan and impairs cognition via perturbation of myelination and synapse formation. However, comprehensive analysis of Klotho knockout effects on mammalian brain transcriptomics is lacking. Here, we report that Klotho knockout alters the levels of aging- and cognition related mRNAs, long non-coding RNAs, microRNAs and tRNA fragments.
View Article and Find Full Text PDFBackground: Fetuin-A inhibits precipitation of calcium-phosphate crystals by forming calciprotein particles (CPP). A novel T50 test, which measures transformation time from primary to secondary CPP, is an index for calcification propensity. Both lower fetuin-A and shorter T50 levels were associated with cardiovascular disease (CVD) risk in patients with chronic kidney disease (CKD).
View Article and Find Full Text PDFTo clarify the taxonomic status of salamanders from Tsushima Islands, Japan, we examined two species of salamanders, Hynobius tsuensis and Hynobius sp. from Tsushima Islands, and compared them with H. nebulosus from Kyushu.
View Article and Find Full Text PDFPhosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.
Arterioscler Thromb Vasc Biol
March 2024
Article Synopsis
- Hyperphosphatemia, or high phosphate levels, is common in patients with kidney issues and can lead to an increased risk of cardiovascular diseases, even at normal phosphate levels within the general population.
- Regulation of phosphate in the body involves signals from multiple organs and hormones that control its absorption and excretion, highlighting the complexity of this nutrient’s management.
- There is ongoing research into therapies that can effectively target phosphate levels and their cardiovascular effects, but current treatments primarily focus on reducing phosphate absorption rather than treating the resulting health complications directly.
Article Synopsis
- Individuals with chronic kidney disease (CKD) experience significant age-related loss of muscle strength in the lower extremities, which affects blood flow within the kidneys.
- This study examined the relationship between lower extremity muscle strength/function and kidney blood flow in 276 people, both with and without CKD, using tests for muscle strength and Doppler ultrasound to measure kidney hemodynamics.
- Results showed that gait speed and performance in a chair stand test were linked to kidney blood flow, while knee extensor strength did not have the same association; lower muscle strength and function were related to increased kidney blood flow pulsatility in both groups.
New Findings: What is the central question of this study? Does the hormone Klotho affect the myogenic response of muscle cells to mechanical loading or exercise? What is the main finding and its importance? Klotho prevents direct, mechanical activation of genes that regulate muscle differentiation, including genes that encode the myogenic regulatory factor myogenin and proteins in the canonical Wnt signalling pathway. Similarly, elevated levels of klotho expression in vivo prevent the exercise-induced increase in myogenin-expressing cells and reduce exercise-induced activation of the Wnt pathway. These findings demonstrate a new mechanism through which the responses of muscle to the mechanical environment are regulated.
View Article and Find Full Text PDFOverexpression of the longevity gene Klotho prolongs, while its knockout shortens lifespan and impairs cognition via altered fibroblast growth factor signaling that perturbs myelination and synapse formation; however, comprehensive analysis of Klotho's knockout consequences on mammalian brain transcriptomics is lacking. Here, we report the altered levels under Klotho knockout of 1059 long RNAs, 27 microRNAs (miRs) and 6 tRNA fragments (tRFs), reflecting effects upon aging and cognition. Perturbed transcripts included key neuronal and glial pathway regulators that are notably changed in murine models of aging and Alzheimer's Disease (AD) and in corresponding human post-mortem brain tissue.
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- - Hyperphosphatemia in patients with end-stage renal disease is linked to poor health outcomes, but the exact molecular mechanisms involved are not well understood.
- - Research suggests that calciprotein particles (CPPs), linked to high serum phosphorus levels, may contribute to health issues by causing calcification and inflammation in blood vessels.
- - A study using hyperphosphatemic pigs showed that removing CPPs from the blood with a special adsorption column improved survival and reduced complications, highlighting CPPs as a potential target for new treatments in hemodialysis patients.
Article Synopsis
- - The study investigates how the inappropriate activation of the renin-angiotensin system (RAS) might affect the relationship between heart and kidney function (cardio-renal syndrome) in middle-aged and older adults, particularly those with chronic kidney disease.
- - Researchers measured urinary angiotensinogen (AGT) levels, which indicate RAS activity, along with other hemodynamic parameters and biomarkers in 282 participants, using specialized techniques like applanation tonometry and duplex ultrasonography.
- - Results showed a correlation between urinary AGT levels and important health indicators like aortic blood pressure and renal blood flow, suggesting that AGT could play a significant role in the cardiovascular and renal health of older adults.
Article Synopsis
- Paraneoplastic IgA nephropathy (IgAN) is a rare condition where symptoms of IgAN appear in patients with certain cancers, and its link to malignancy is still debated.
- A 68-year-old Japanese man with glottic cancer was diagnosed with nephrotic syndrome due to IgAN, which was confirmed by a renal biopsy showing a specific type of glomerulonephritis.
- After successful treatment of his cancer, his kidney symptoms improved, suggesting that IgAN might be associated with glottic cancer, and further research on the role of certain IgA types in this context is warranted.
Calciprotein particles (CPPs) are mineral-protein complexes containing solid-phase calcium-phosphate and the serum protein fetuin-A. CPPs are dispersed in the blood as colloids. Previous clinical studies revealed that circulating levels of CPPs were correlated with inflammation and vascular calcification/stiffness in patients with chronic kidney disease (CKD).
View Article and Find Full Text PDFCalcium phosphate microcrystallopathy as a paradigm of chronic kidney disease progression.
Curr Opin Nephrol Hypertens
July 2023
Purpose Of Review: Calciprotein particles (CPP) are colloidal mineral-protein complexes mainly composed of solid-phase calcium phosphate and serum protein fetuin-A. CPP appear in the blood and renal tubular fluid after phosphate intake, playing critical roles in (patho)physiology of mineral metabolism and chronic kidney disease (CKD). This review aims at providing an update of current knowledge on CPP.
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- This study examines the role of phosphate in the development of chronic kidney disease (CKD) in dolphins by analyzing tissue samples from a deceased captive dolphin.
- Although the dolphin had normal renal function until shortly before death, it exhibited medullary calcification and kidney injury due to myocarditis.
- Experiments indicated that high phosphate levels can harm dolphin kidney cells, but magnesium may help reduce this damage, suggesting a link between phosphate exposure, kidney injury, and potential treatment options.
Article Synopsis
- Acute kidney injury (AKI) increases the chances of serious heart events and mortality, but the reasons behind this link are still unclear.
- Research shows that a decrease in the anti-aging factor klotho may worsen heart damage following AKI, as seen in experiments with mice that had reduced klotho levels.
- Specifically, the study found that mice with lower klotho expression experienced impaired heart cell function and more disturbances in calcium handling after AKI, suggesting that targeting klotho expression could be a new treatment strategy for protecting heart health in AKI patients.
Article Synopsis
- Calcium phosphate (CaP) particles can form in the kidneys due to excessive phosphate excretion, potentially leading to cellular damage and renal dysfunction.
- This study employs advanced microscopy techniques, including fluorescent staining and energy-dispersive X-ray spectroscopy (EDS), to effectively observe and analyze CaPs in kidney tissue.
- Findings reveal that variations of CaPs formed from different dietary phosphate levels can be identified, providing valuable insights into their elemental composition and significance in kidney health.
Calciprotein particles (CPPs) are colloids composed of solid-phase calcium-phosphate and serum protein fetuin-A. CPPs form a polydispersed system with different particle size and density. CPPs with specific physical properties can induce calcification and innate immune responses in cultured cells.
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