Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.
Background: Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by a rapid decline in renal function that often causes end-stage renal disease. Although it is important to predict renal outcome in RPGN before initiating immunosuppressive therapies, no simple prognostic indicator has been reported. The aim of this study was to investigate the associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to renal outcomes in patients with RPGN. Methods: Forty-four patients with a clinical diagnosis of RPGN who underwent renal biopsy were enrolled. The relationships between NLR and PLR and renal outcome after 1 year were investigated. Results: NLR and PLR were significantly higher in patients with preserved renal function in comparison to patients who required maintenance hemodialysis (p < 0.05 and p < 0.01, respectively). An NLR of 4.0 and a PLR of 137.7 were the cutoff values for renal outcome (area under the curve, 0.782 and 0.819; sensitivity, 78.4% and 89.2%; specificity, 71.4% and 71.4%, respectively). Furthermore, an NLR of 5.0 could predict recovery from renal injury in patients requiring hemodialysis (area under the curve, 0.929; sensitivity, 83.3%; specificity, 85.7%). Conclusion: NLR and PLR could be candidates for predicting renal outcomes in patients with RPGN.
Background: Sarcopenia is a major health issue especially in patients on maintenance hemodialysis. Low skeletal muscle mass is included in the diagnostic criteria for sarcopenia. The skeletal muscle mass is usually evaluated by modalities such as bioimpedance analysis (BIA) or dual-energy x-ray absorptiometry, however the assessment of skeletal muscle mass using computed tomography (CT) images has not been established. The purpose of the study was to investigate the feasibility of the assessment of skeletal muscle mass using CT image in hemodialysis patient.Methods: Skeletal muscle mass index (SMI) was measured by BIA and psoas muscle index (PMI) was measured by cross-sectional CT image in 131 patients. The relationship between SMI and PMI and the diagnostic ability of PMI for low muscle mass were evaluated. Furthermore, the patients were followed up and long-term survival in patients with low and high PMI were compared.Results: PMI measured at L3 vertebral level was strongly correlated with SMI (r = 0.597, p < 0.001). Age, sex, and SMI were the influencing factor for PMI. Patients with low PMI showed higher incidence rates of mortality during the follow up.Conclusions: PMI assessed by CT image can be an alternative to BIA in patients with hemodialysis.
Background: Kidney size is associated with renal function, however it is not elucidated whether kidney size is a risk for the progression of chronic kidney disease. The aim of this study was to investigate the predictive value of morphological evaluation of kidney size by ultrasonography for the progression of renal dysfunction. Methods: Morphological parameters including kidney length, volume, cortical thickness, and medullary thickness were measured by ultrasonography in 87 patients with chronic kidney disease, and adjusted by body size. Renal functions at baseline and after 2 years were measured and the associations of morphological parameters to decline in renal function over 2 years were analyzed. Results: Height-adjusted cortical thickness was correlated to decline in renal function (r = 0.426, p < 0.001). Height-adjusted cortical thickness could predict renal dysfunction with the area under the curve of 0.786, and height-adjusted cortical thickness of 4.0 mm/cm was a cut off value with a sensitivity of 72.5% and a specificity of 80.0% for the risk of a more than 30% decline in renal function or initiation of dialysis. Conclusions: We provide new insights into the utility of measuring cortical thickness by ultrasonography for predict future renal impairment.
Gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is an activatable fluorescent probe that can be activated by γ-glutamyltranspeptidase (GGT). The expression of GGT in the kidney, which is one of the major organs exhibiting enhanced GGT expression, is exclusively localised to the cortex. Here, we aimed to investigate the feasibility of gGlu-HMRG as a probe for the on-site assessment of renal biopsy specimens. gGlu-HMRG fluorescent probe was applied to the renal proximal tubular epithelial cells and cortical collecting duct cells in vitro, mouse kidneys ex vivo, and human biopsy specimens. In addition, the fluorescence intensities in the cortex and the medulla were comparatively evaluated in the biopsy specimens. The fluorescence signal was rapidly detected in the renal proximal tubular epithelial cells, whereas that in the cortical collecting duct cells was not detected. The fluorescence signal was detected in the mouse kidneys ex vivo without markedly affecting the tissue morphology. In the human biopsy specimens, the fluorescence signal in the cortex was significantly distinct from that in the medulla (p < 0.05). Thus, this fluorescent probe can be used to distinctly identify the renal cortex in the biopsy specimens.
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