Kidney Research and Clinical Practice最新文献

Background: In maintenance hemodialysis (MHD) patients, vascular calcification can be detected not only in coronary vessels but also in ocular areas. However, ophthalmic examinations are not sufficiently validated to measure the degree of vascular calcification.

Methods: This study was performed prospectively, involving 32 MHD patients. Calcium deposition in the cornea and conjunctiva was checked using a slit lamp and anterior photography. Conjunctival and corneal calcification (CCC) score was calculated and the severity of CCC was graded. Extent of invasion in the corneal limbus and center was identified. Coronary artery calcium (CAC) deposit was scored using computer tomography, and cardiac function was investigated by echocardiogram. We divided patients into two groups: mild and moderate/severe groups according to the CCC scores.

Results: Mean CAC scores were 354.6 and 1,494.2 in the mild and moderate/severe groups. Mean extent of invasion in the corneal limbus and center was significantly higher in the moderate/severe groups than in the mild group. Parathyroid hormone was significantly higher in the moderate/severe groups than in the mild group and ejection fraction was significantly lower in the moderate/severe groups than in the mild group. The CCC score was positively associated with the CAC score, the extent of invasion in the corneal limbus and center, and the parathyroid hormone level. The extent of invasion in the corneal limbus and center was positively associated with the CAC score. The CCC score was negatively associated with ejection fraction.

Conclusion: The CCC score and the extent of invasion in the corneal limbus and center can predict vascular calcification in MHD patients.

Background: Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD.

Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA).

Results: A total of 27 and 23 metabolites from the serum and urine of FD mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice.

Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

Donor-derived cell-free DNA (dd-cfDNA) based liquid kidney biopsies have the potential to detect the chances of kidney transplant rejection. Several studies have found that dd-cfDNA can be used to determine the risk of kidney transplant rejection and may correlate with antibody-mediated rejection (ABMR), T cell-mediated rejection (TCMR), and estimated glomerular filtration rate (eGFR). A high concentration of dd-cfDNA in the body fluids may indicate possible transplant rejection since dd-cfDNA is released as a result of apoptotic and necrotic processes initiated by the recipient's immune system. dd-cfDNA assays have advantages over conventional biopsies since they are noninvasive, and therefore, have the potential to provide a safe and reliable biomarker. Different dd-cfDNA levels have been reported above a number of cutoff thresholds: ABMR at 2.45% and TCMR at 1.3%, compared with 0.44% in healthy patients; and eGFR at 2.5%, a decrease of 25% compared with healthy patients. These results indicate the levels of dd-cfDNA that may be used to signal possible kidney rejection. dd-cfDNA assay is a rapid technique, making it particularly useful in emergencies, and further research into its use in the study of kidney rejection should prove beneficial.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms.

Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements.

Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-β)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group.

Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-β decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

The worldwide prevalence of chronic kidney disease (CKD) is high and growing, making CKD a leading cause of mortality. Skeletal muscle wasting, sometimes called sarcopenia or protein-energy wasting, is a frequent, serious consequence of CKD that reduces muscle strength and function, diminishes the quality of life of patients, and raises their risk of comorbidities and death. Muscle atrophy results from a disturbance in muscle protein balance that results from some combination of an increased rate of protein degradation, a decreased rate of protein synthesis, and dysfunctional muscle regeneration. Development of therapeutic strategies to ameliorate muscle loss, or maintain muscle mass, is challenging because of the multifactorial nature of the signals that alter protein homeostasis. This review discusses the cellular signals and mechanisms that negatively alter protein turnover in skeletal muscle during CKD.