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.

Hyperuricemia has been increasingly recognized as a modifiable contributor to chronic kidney disease (CKD) progression. Although the traditional classification of hyperuricemia distinguished between renal underexcretion and renal overload types, recent studies suggest that hyperuricemia in patients with CKD can result from heterogeneous excretory defects, including glomerular under-filtration and tubular over-reabsorption. These distinct phenotypes may drive divergent renal injury mechanisms. Experimental and clinical data reveal that monosodium urate crystals and soluble uric acid independently induce renal damage through oxidative stress, inflammasome activation, and endothelial dysfunction. Furthermore, clinical investigations showed inconsistent associations between serum uric acid levels and renal outcomes, suggesting that serum levels alone may not fully reflect urate-related renal risk. This has prompted increasing interest in uricosuric agents, particularly the selective urate reabsorption inhibitors (SURIs), which target tubular urate handling. Urate transporter 1 inhibitors have shown promise in enhancing urinary uric acid excretion and potentially preserving kidney function, especially in patients with CKD. In this review, we summarize the current evidence linking the emerging pathophysiological classification of hyperuricemia, mechanisms or urate-induced kidney injury, and therapeutic interventions. These insights may inform individualized approaches to urate-lowering therapy in CKD and support future research into phenotype-guided treatment strategies.

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.

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: The indications for endoscopic submucosal dissection (ESD) for gastric cancer are based on preoperative histological assessment; however, examination of tissue biopsy is not always reliable as only a limited portion of the lesion can be obtained. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammatory response and are potentially associated with the grade of malignancy in gastric cancer. We aimed to investigate the association between NLR and PLR and the histology of gastric cancer. Methods: This study included 218 patients who underwent ESD for gastric cancer. The relationship between NLR/PLR and histological diagnosis was investigated. Results: Patients with adenocarcinomas showed significantly higher NLR and PLR than those with adenomas (p < 0.001 and p < 0.05, respectively). Further, patients with undifferentiated adenocarcinoma showed a significantly higher NLR (p < 0.05) than those with differentiated adenocarcinoma. Conclusion: This study suggests that NLR could be a useful marker for assessing early gastric cancer.

Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.