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Th17 cells play an important role in psoriasis. The differentiation of naïve CD4+ T cells into Th17 cells depends on glycolysis as the energy source. CD147/basigin, an integral transmembrane protein belonging to the immunoglobulin superfamily, regulates glycolysis in association with monocarboxylate transporters (MCTs)-1 and -4 in cancer cells and T cells. We examined whether CD147/basigin is involved in the pathogenesis of psoriasis in humans and psoriasis-model mice. The serum level of CD147 was increased in patients with psoriasis, and the expression of CD147 and MCT-1 was elevated in their dermal CD4+ RORγt+ T cells. In vitro, the potential of naïve CD4+ T cells to differentiate into Th17 cells was abrogated in CD147−/− T cells. Imiquimod (IMQ)-induced psoriatic dermatitis was significantly milder in CD147−/− mice and bone marrow chimeric mice lacking CD147 in the hematopoietic cells of myeloid lineage. These findings demonstrate that CD147 is essential for the development of psoriasis via the induction of Th17 cell differentiation.

Acute T cell-mediated rejection (ATCMR) is a severe negative outcome of kidney transplantation; however, it currently has no reliable marker in Japan. This cross-sectional study was conducted at the Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 2016 to 2018 to determine whether plasma or urinary Basigin/CD147 is an effective marker of ATCMR. Plasma and urinary samples were obtained when episode graft biopsies were performed. Forty-six kidney transplant recipients received graft biopsies. Three of them missed plasma and urinary samples and three in ATCMR were on postrejection treatment. Graft biopsy results revealed ATCMR in 12 of them, calcineurin inhibitor nephrotoxicity (CIN) in nine, chronic active antibody-mediated rejection (CAAMR) in nine, BK nephropathy, recurrence IgA nephropathy, necrotic glomerulonephritis, and infection-related glomerulonephritis in one each, and other complications in six. The urinary Basigin/CD147 levels of patients in the ATCMR group [759.4 (490.0, 843.0)] pg/gCre were significantly higher than the levels of patients in the CAAMR [247.0 (157.1, 288.8)] and CIN groups [379.1 (264.7, 456.7)] pg/gCre (  < 0.001). No statistical difference in plasma Basigin/CD147 levels was observed between those groups. At a urinary Basigin/CD147 of 631.5 µg/gCre, 75% sensitivity and 84% specificity with an area under the curve of 0.80 were attained for the diagnosis of graft rejection. Urinary Basigin/CD147 may be a potential marker for ATCMR in kidney transplant recipients. Further studies will be needed to clarify the effectiveness of Basigin/CD147.

Normal saline (NS) is recommended for the treatment of chloride-depletion alkalosis (CDA). However, its use in patients with drinking water restrictions or fluid volume deficiencies may lead to hypernatremia. We report the case of a 42-year-old Japanese man with ileus due to sigmoidal volvulus, who presented with CDA. After endoscopic decompression, NS was administered to treat the CDA. Despite the administration of NS, CDA persisted and hypernatremia developed. The infusion was then changed to high cation-gap amino acids (HCG-AA), which improved both metabolic alkalosis and hypernatremia. Thus, HCG-AA may be useful for the treatment of hypernatremia in patients with CDA.

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. This is the third article in this series that focuses on water and electrolyte disturbances caused by novel pharmacological agents for kidney disease and cancer. The advent of novel pharmacological agents in cardiorenal medicine and oncology has introduced both therapeutic benefits and challenges in managing medication-induced water and electrolyte disturbances. These medications, including sodium–glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (ns-MRAs), and immune checkpoint inhibitors (ICIs), significantly impact water and electrolyte homeostasis. SGLT2 inhibitors used widely in diabetes mellitus, heart failure, and chronic kidney disease mitigate hyperkalemia and hypomagnesemia but increase the risk of hypernatremia in patients on fluid restriction. Conversely, they are beneficial for managing hyponatremia in the syndrome of inappropriate antidiuresis (SIAD). ns-MRAs, prescribed for diabetic kidney disease, exhibit a high risk of hyperkalemia, particularly when combined with renin–angiotensin system inhibitors. ICIs, a breakthrough in oncology, frequently induce hyponatremia through immune-related adverse events, such as hypophysitis and non-immune-related adverse events like SIAD. Understanding the pathophysiology of these disturbances and implementing timely interventions, including hormone replacement and water and electrolyte management, is critical for optimizing treatment outcomes.

ObjectivesWe aimed to examine the validity of the quick Sequential Organ Failure Assessment (qSOFA) score for mortality and bacteraemia risk assessment in Japanese haemodialysis patients.DesignThis is a retrospective multicentre cohort study.SettingThe six participating hospitals are tertiary-care institutions that receive patients on an emergency basis and provide primary, secondary and tertiary care. The other participating hospital is a secondary-care institution that receives patients on an emergency basis and provides both primary and secondary care.ParticipantsThis study included haemodialysis outpatients admitted for bacteraemia suspicion, who had blood drawn for cultures within 48 hours of their initial admission.Primary and secondary outcome measuresThe primary outcome measure was overall in-hospital mortality. Secondary outcomes included 28-day in-hospital mortality and the incidence of bacteraemia diagnosed based on blood culture findings. The discrimination, calibration and test performance of the qSOFA score were assessed. Missing data were handled using multiple imputation.ResultsAmong the 507 haemodialysis patients admitted with bacteraemia suspicion between August 2011 and July 2013, the overall in-hospital mortality was 14.6% (74/507), the 28-day in-hospital mortality was 11.1% (56/507) and the incidence of bacteraemia, defined as a positive blood culture, was 13.4% (68/507). For predicting in-hospital mortality among haemodialysis patients, the area under the receiver operating characteristic curve was 0.61 (95% CI 0.56–0.67) for a qSOFA score ≥2. The Hosmer-Lemeshow χ2 statistics for the qSOFA score as a predictor of overall and 28-day in-hospital mortality were 5.72 (p=0.02) and 7.40 (p<0.01), respectively.ConclusionOn external validation, the qSOFA score exhibited low diagnostic accuracy and miscalibration for in-hospital mortality and bacteraemia among haemodialysis patients.

Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid β-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg -deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane–selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. The seminar features dynamic case-based discussions, some of which are included as self-assessment questions in this series. The second article in this series focuses on treatment of hyponatremia, a common water and electrolyte disorder frequently encountered in clinical practice. Hyponatremia presents diagnostic challenges due to its various etiologies and the presence of co-morbidities that affect water and electrolyte homeostasis. Furthermore, limited evidence, including a lack of robust randomized controlled trials, complicates treatment decisions and increases the risk of poor outcomes from inappropriate management of both acute and chronic hyponatremia. This review provides a comprehensive overview of treatment of hyponatremia for better comprehension and improved clinical practice.

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar includes lively discussions based on cases, which are also partly included in this series as self-assessment questions. The first article in this series focuses on pathophysiology, symptoms, outcomes, and evaluation of hyponatremia, a common water and electrolyte disorder in clinical practice. Diagnosing the root cause(s) of hyponatremia can be challenging due to various etiologies and co-morbidities that affect water and electrolyte homeostasis, which can result in inappropriate management and worse outcomes in acute and chronic hyponatremia. This review provides an overview of pathophysiology, symptoms, outcomes, and evaluation of hyponatremia for better comprehension and improved clinical practice.