Understanding factors associated with physical activity (PA) is important to promote PA. The purpose of the present study was to investigate factors associated with achieving PA guideline in 293 Japanese adolescents (140 boys and 153 girls). Time spent in moderate to vigorous PA (MVPA) was accessed by using accelerometers. Based on MVPA, the participants were classified as “Active” (≥60 min/day of MVPA) or “Inactive” (<60 min/day of MVPA). Anthropometry, age, screen time, mental health, participation in after-school sport activities, sleep status, and breakfast status were measured as factors potentially associated with achieving PA guideline. Adjusted logistic regression analyses revealed that after-school sports activities were positively associated with the probability of being Active for both sexes (odds ratios [ORs] [95% confidence intervals (CI)] = 3.90 [1.13-13.49] for boys, 4.80 [1.80-12.81] for girls). In addition, body fat was negatively associated with a reduced likelihood of being Active for girls (ORs [95%CI] = 0.93 [0.87-0.97]). Two factor ANOVA revealed that those in Inactive group had significantly lower PA levels than those in Active group on both regular curriculum and extra-curriculum (F _{(1, 138)} = 152.50 for boys, F _{(1, 151)} = 181.95 for girls, p < 0.001). In addition, for girls, there was a significant interaction effect between domain (regular curriculum vs. extra-curriculum) and after-school sport activities (F _{(1, 151)} = 4.91, p = 0.028), suggesting that obtaining higher PA levels on extra-curriculum might be difficult for those who do not belong to any after-school sport activities. Therefore, promoting PA on regular curriculum (i.e., physical education lessons and recess) might be alternative ways to increase PA levels for those individuals. Furthermore, special attention may be needed for girls who have higher body fat to promote PA.

The purpose of the present study was to examine the associations between physical fitness and body fatness with blood lipid profile in 231 Japanese children and adolescents (12.1 ± 1.5 years). The primary outcomes of the present study were a lipid risk score which was calculated by summing up z scores of three lipid items (triglycerides, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol). Physical fitness was assessed by using the Japanese standardised fitness test. For body fatness, a percentage of overweight was calculated with using age-, sex-, height-specific standardised body mass. For combined analysis (fitness × fatness), the participants were cross-tabulated into four groups (Non-Obese/Higher-Fit, Non-Obese/Lower-Fit, Obese/Higher-Fit, and Obese/Lower-Fit). The results demonstrated that the participants in fitness categories A/B [most fit] and C [middle] demonstrated the lower (better) lipid risk score than the participants in fitness categories D/E [least fit] (F _{(2, 222)} = 6.03, p = .003). For body fatness, the lipid risk score in obese group was significantly higher (worse) than that in thin and normal groups (F _{(2, 222)} = 6.08, p = .004). The combined analysis showed that there was a significant interaction (fitness × fatness) on the lipid risk score (F _{(1, 221)} = 4.05, p = .047), suggesting that Obese/Lower-Fit group had the worst risk score compared to the other groups. The present study suggests that improving both fitness and body fatness might be important for better lipid profile in Japanese children and adolescents.

Diabetic kidney disease is the leading cause of end-stage kidney disease, and it remains a major challenge. Many factors, such as glomerular hyperfiltration, oxidative stress, inflammation, hypoxia, and epigenetics, are associated with the progression of diabetic kidney disease; however, the whole mechanism is not yet completely understood. No specific treatment for diabetic kidney disease has been established, so new approaches are being explored extensively. Sodium-glucose cotransporter 2 inhibitors have shown renoprotective effects in several human clinical trials. Glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported to be effective in diabetic kidney disease, and novel therapeutic candidates are also being examined. In the TSUBAKI trial, a nuclear factor erythroid 2-related factor 2 activator, bardoxolone methyl, improved the glomerular filtration rate of diabetic kidney disease patients. Similarly, new agents that act in the oxidative stress and inflammation pathways are of major interest, such as pentoxifylline, apoptosis signal-regulating kinase-1 inhibitors, C-C chemokine receptor 2 inhibitors, and Janus kinase-1/2 inhibitors. Endothelin-1 receptor A antagonists and soluble guanylate cyclase stimulators are also expected to affect renal hemodynamics. Some preclinical studies suggest that hypoxia-inducible factor prolyl hydroxylase inhibitors, which influence multiple inflammations and oxidative stress pathways, reduce albuminuria in diabetic kidney disease. Advanced glycation end-product inhibitors and treatments related to epigenetics have also shown promise as potential diabetic kidney disease treatments in preclinical studies. The discovery of new targets could provide new therapeutic options for overcoming diabetic kidney disease.

Diabetic kidney disease (DKD) is the major cause of end-stage kidney disease. However, only renin-angiotensin system inhibitor with multidisciplinary treatments is effective for DKD. In 2019, sodium-glucose cotransporter 2 (SGLT2) inhibitor showed efficacy against DKD in Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, adding a new treatment option. However, the progression of DKD has not been completely controlled. The patients with transient exposure to hyperglycemia develop diabetic complications, including DKD, even after normalization of their blood glucose. Temporary hyperglycemia causes advanced glycation end product (AGE) accumulations and epigenetic changes as metabolic memory. The drugs that improve metabolic memory are awaited, and AGE inhibitors and histone modification inhibitors are the focus of clinical and basic research. In addition, incretin-related drugs showed a renoprotective ability in many clinical trials, and these trials with renal outcome as their primary endpoint are currently ongoing. Hypoxia-inducible factor prolyl hydroxylase inhibitors recently approved for renal anemia may be renoprotective since they improve tubulointerstitial hypoxia. Furthermore, NF-E2–related factor 2 activators improved the glomerular filtration rate of DKD patients in Bardoxolone Methyl Treatment: Renal Function in chronic kidney disease/Type 2 Diabetes (BEAM) trial and Phase II Study of Bardoxolone Methyl in Patients with Chronic Kidney Disease and Type 2 Diabetes (TSUBAKI) trial. Thus, following SGLT2 inhibitor, numerous novel drugs could be utilized in treating DKD. Future studies are expected to provide new insights.