Lifetime risk (LTR) evaluates the absolute risk of developing a disease during the remainder of one's life. It can be a useful tool, enabling the general public to easily understand their risk of ...stroke. No study has been performed to determine the LTR of cardiovascular disease in patients with chronic kidney disease (CKD) with or without hypertension; therefore, we performed this study in an Asian population. We followed 1525 participants (66.0% women; age 63.1 years) in the general population of Ohasama, Japan. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m
and/or proteinuria. Hypertension was defined as a systolic/diastolic blood pressure ≥140/≥90 mmHg and/or the use of antihypertensive medication. We calculated the sex-specific LTR of stroke adjusted for the competing risk of death. During the mean follow-up period of 16.5 years, a first stroke occurred in 238 participants. The 10-year risk of stroke at the age of 45 years was 0.0% for men and women. The LTRs of stroke at the index age of 45 years (men/women) were 20.9%/14.5% for participants without CKD and hypertension, 34.1%/29.8% for those with CKD but not hypertension, 37.9%/27.3% for those with hypertension but not CKD, and 38.4%/36.4% for those with CKD and hypertension. The LTRs of stroke tended to be higher in younger participants than in older participants with CKD and/or hypertension. CKD contributed to the LTR of stroke, as did hypertension. The prevention of CKD and hypertension can reduce the LTR of stroke, especially in young populations.
Nephrolithiasis is a common renal disease with no effective medication. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, an anti-diabetic agent, have diuretic and anti-inflammatory properties and ...could prevent nephrolithiasis. Here, we investigated the potential of SGLT2 inhibition against nephrolithiasis using large-scale epidemiological data, animal models, and cell culture experiments.
This study included the data of diabetic patients (n = 1,538,198) available in the Japanese administrative database and divided them according to SGLT2 inhibitor prescription status. For animal experiments, renal calcium oxalate stones were induced by ethylene glycol in Sprague-Dawley rats, and phlorizin, an SGLT1/2 inhibitor, was used for the treatment. The effects of SGLT2-specific inhibition for renal stone formation were assessed in SGLT2-deficient mice and a human proximal tubular cell line, HK-2.
Nephrolithiasis prevalence in diabetic men was significantly lower in the SGLT2 inhibitor prescription group than in the non-SGLT2 inhibitor prescription group. Phlorizin attenuated renal stone formation and downregulated the kidney injury molecule 1 (Kim1) and osteopontin (Opn) expression in rats, with unchanged water intake and urine volume. It suppressed inflammation and macrophage marker expression, suggesting the role of the SGLT2 inhibitor in reducing inflammation. SGLT2-deficient mice were resistant to glyoxylic acid-induced calcium oxalate stone formation with reduced Opn expression and renal damages. High glucose-induced upregulation of OPN and CD44 and cell surface adhesion of calcium oxalate reduced upon SGLT2-silencing in HK-2 cells.
Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis.
Display omitted
•SGLT2 inhibitors reduce nephrolithiasis in diabetic men based on Japanese database.•Phlorizin ameliorates renal CaOx stone formation, and subsequent damages in rats.•SGLT2 deficiency suppresses renal CaOx stone, inflammation, and damage in mice.•SGLT2 silencing inhibits OPN upregulation and CaOx crystal-cell adhesion in vitro.•SGLT2 inhibitors may be a promising therapeutic approach against nephrolithiasis.
Chronic kidney disease (CKD) is a global health burden. Previous studies have shown a J- or U-shaped association between serum uric acid (SUA) and cardiovascular mortality. We assessed the risk of ...CKD incidence in a refined SUA category in middle-aged adults stratified by sex.
We analyzed data from 138,511 participants <65 years old (29.6% women; mean age 44.1 years) without CKD at baseline acquired from the JMDC database. The Cox model was used to assess the adjusted hazard ratio (HR).
During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The fully adjusted HRs (95% confidence interval CI, p-value) for CKD incidence in men with SUA <4.0, 10.0–10.9 and ≥ 11.0 mg/dL compared to men with SUA 4.0–4.9 mg/dL were 1.13 (1.01–1.26, p = 0.030), 1.98 (1.32–2.97, p = 0.0010), and 3.74 (1.68–8.35, p = 0.0013), respectively. The fully adjusted HRs for CKD incidence in women with SUA <4.0, 8.0–8.9, and ≥9.0 mg/dL compared to women with SUA 4.0–4.9 mg/dL were 1.08 (1.01–1.16, p = 0.032), 2.39 (1.07–5.35, p = 0.034), and 3.20 (0.80–12.8, p = 0.10), respectively.
Both high and low SUA levels were identified as risk factors for CKD incidence in middle-aged men and women. The association of SUA levels with the increase in the risk of CKD incidence differed by sex, and the range of SUA levels associated with an increase in the risk of CKD incidence varied by sex.
Display omitted
•The association of serum uric acid (SUA) levels with the increase in the risk of chronic kidney disease (CKD) incidence differed by sex.•The range of SUA levels associated with an increase in the risk of CKD incidence varied by sex.
The title compound, 2-ethylhexyl-4-methoxycinnamate (2EH4MC), is known as a typical ingredient of sunscreen cosmetics that effectively converts the absorbed UV-B light to thermal energy. This energy ...conversion process includes the nonradiative decay (NRD): trans–cis isomerization and finally going back to the original structure with a release of thermal energy. In this study, we performed UV spectroscopy for jet-cooled 2EH4MC to investigate the electronic/geometrical structures as well as the NRD mechanism. Laser-induced-fluorescence (LIF) spectroscopy gave the well-resolved vibronic structure of the S1–S0 transition; UV–UV hole-burning (HB) spectroscopy and density functional theory (DFT) calculations revealed the presence of syn and anti isomers, where the methoxy (−OCH3) groups orient in opposite directions to each other. Picosecond UV–UV pump–probe spectroscopy revealed the NRD process from the excited singlet (S1 (1ππ*)) state occurs at a rate constant of ∼1010–1011 s–1, attributed to internal conversion (IC) to the 1nπ* state. Nanosecond UV–deep UV (DUV) pump–probe spectroscopy identified a transient triplet (T1 (3ππ*)) state, whose energy (from S0) and lifetime are 18 400 cm–1 and 20 ns, respectively. These results demonstrate that the photoisomerization of 2EH4MC includes multistep internal conversions and intersystem crossings, described as "S1 (trans, 1ππ*) → 1nπ* → T1 (3ππ*) → S0 (cis)".
Increased central venous pressure in congestive heart failure is responsible for renal dysfunction, which is mediated by renal venous congestion. Pericyte detachment from capillaries after renal ...congestion might trigger renal fibrogenesis via pericyte-myofibroblast transition (PMT). Platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated in our recently established renal congestion model. This study was designed to determine whether inhibition of the PDGFR pathway could suppress tubulointerstitial injury after renal congestion.
The inferior vena cava between the renal veins was ligated in male Sprague-Dawley rats, inducing congestion only in the left kidney. Imatinib mesylate or vehicle were injected intraperitoneally daily from 1 day before the operation. Three days after the surgery, the effect of imatinib was assessed by physiological, morphological and molecular methods. The inhibition of PDGFRs against transforming growth factor-β1 (TGFB1)-induced fibrosis was also tested in human pericyte cell culture.
Increased kidney weight and renal fibrosis were observed in the congested kidneys. Upstream inferior vena cava (IVC) pressure immediately increased to around 20 mmHg after IVC ligation in both the imatinib and saline groups. Although vasa recta dilatation and pericyte detachment under renal congestion were maintained, imatinib ameliorated the increased kidney weight and suppressed renal fibrosis around the vasa recta. TGFB1-induced elevation of fibrosis markers in human pericytes was suppressed by PDGFR inhibitors at the transcriptional level.
The activation of the PDGFR pathway after renal congestion was responsible for renal congestion-induced fibrosis. This mechanism could be a candidate therapeutic target for renoprotection against renal congestion-induced tubulointerstitial injury.
Predicting and preventing new-onset chronic kidney disease (CKD) through blood pressure (BP) measurements is worthwhile. This study assessed the risk of CKD, which was defined as proteinuria and/or ...an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m
, according to cross-classification by systolic and diastolic BP (SBP and DBP). This retrospective population-based cohort study analyzed data from 1,492,291 participants without CKD and without antihypertensive treatment in the JMDC database, which contains the annual health check-up data of Japanese aged <75 years. During a mean follow-up of 3.2 years, CKD incidence, proteinuria, and eGFR <60 mL/min/1.73 m
occurred in 92,587, 67,021, and 28,858 participants, respectively. When the SBP/DBP <120/<80 mmHg group was set as a reference, both high SBP and DBP were significantly associated with an elevated CKD risk. DBP tended to be more strongly associated with CKD risk than SBP; the hazard ratio of CKD was 1.44-1.80 in the group with SBP/DBP of 130-139/≥90 mmHg and 1.23-1.47 in the group with SBP/DBP of ≥140/80-89 mmHg. A similar result was observed for developing proteinuria and eGFR <60 mL/min/1.73 m
. SBP/DBP ≥150/<80 mmHg was strongly associated with an elevated CKD risk due to the increased risk of eGFR decline. High BP, especially isolated high DBP levels, is a significant risk factor for CKD among individuals around middle age without kidney disease. Moreover, attention should be paid to kidney function, particularly eGFR decline, in the case of low DBP with extremely high SBP levels.
Abstract
Background
We investigated the association between ambulatory blood pressure (BP) and the risk of home hypertension in a normotensive population and whether considering ambulatory BP ...improves the 10-year prediction model for home hypertension risk, which was developed in the previous Ohasama Study.
Methods
In this prospective study, we followed up with 410 participants (83.2% women; age, 53.6 years) without a home and ambulatory hypertension in the general population of Ohasama, Japan. The Cox model was used to assess the hazard ratios (HRs) for home hypertension (home BP ≥ 135/≥85 mmHg or the initiation of antihypertensive treatment) and model improvement.
Results
During a mean 14.2-year follow-up, 225 home hypertension incidences occurred. The HR (95% confidence interval) for home hypertension incidence per 1-SD higher (=6.76 mmHg) 24-hour systolic BP (SBP) was 1.59 (1.33 to 1.90), after adjustments for possible confounding factors, including baseline home SBP. Harrell’s C-statistics increased from 0.72 to 0.73 (P = 0.11) when 24-hour SBP was added to the basic 10-year home hypertension prediction model, which includes sex, age, body mass index, smoking status, office SBP, and baseline home SBP. Continuous net reclassification improvement (0.53, P < 0.0001) and integrated discrimination improvement (0.028, P = 0.0014) revealed improvement in the model.
Conclusions
A total of 24-hour SBP could be an independent predictor of future home hypertension. Home BP and 24-hour BP can longitudinally influence each other in the long term.
Graphical Abstract
Graphical Abstract
Genetic alterations in adult T‐cell leukemia/lymphoma (ATLL), a T‐cell malignancy associated with HTLV‐1, and their clinical impacts, especially from the perspective of viral strains, are not fully ...elucidated. We employed targeted next‐generation sequencing and single nucleotide polymorphism array for 89 patients with ATLL in Okinawa, the southernmost islands in Japan, where the frequency of HTLV‐1 tax subgroup‐A (HTLV‐1‐taxA) is notably higher than that in mainland Japan, where most ATLL cases have HTLV‐1‐taxB, and compared the results with previously reported genomic landscapes of ATLL in mainland Japan and the USA. Okinawan patients exhibited similar mutation profiles to mainland Japanese patients, with frequent alterations in TCR/NF‐ĸB (eg, PRKCB, PLCG1, and CARD11) and T‐cell trafficking pathways (CCR4 and CCR7), in contrast with North American patients who exhibited a predominance of epigenome‐associated gene mutations. Some mutations, especially GATA3 and RHOA, were detected more frequently in Okinawan patients than in mainland Japanese patients. Compared to HTLV‐1‐taxB, HTLV‐1‐taxA was significantly dominant in Okinawan patients with these mutations (GATA3, 34.1% vs 14.6%, P = .044; RHOA, 24.4% vs 6.3%, P = .032), suggesting the contribution of viral strains to these mutation frequencies. From a clinical viewpoint, we identified a significant negative impact of biallelic inactivation of PRDM1 (P = .027) in addition to the previously reported PRKCB mutations, indicating the importance of integrated genetic analysis. This study suggests that heterogeneous genetic abnormalities in ATLL depend on the viral strain as well as on the ethnic background. This warrants the need to develop therapeutic interventions considering regional characteristics.
Targeted next‐generation sequencing and single nucleotide polymorphism array were applied to analyze aggressive adult T‐cell leukemia/lymphoma in Okinawa, which were not included in prior genomic studies. Our results showed that HTLV‐1 tax subgroup‐A was associated with high alteration frequencies in GATA3 and RHOA. Clinically, biallelic alterations, not heterozygous deletions or mutations, of PRDM1 were significantly associated with poor prognosis.
No studies have demonstrated the association between urinary sodium-to-potassium (Na/K) ratio and all out-of-office blood pressure (BP) home morning and evening BP (self-measured at home), and 24-h, ...daytime, and night-time ambulatory BP in the same cohort. We aimed to assess, which type of out-of-office BP is more strongly associated with urinary Na/K ratio in the general population.
This cross-sectional study was conducted in the general population of Ohasama, Japan. Home and ambulatory BP levels were measured, and 24-h urine samples were obtained from 875 participants (men, 25.5%; mean age, 60.1 years). The urinary Na/K ratio in the 24-h urine samples was calculated.
The median (interquartile range) urinary Na/K ratio was 4.19 (3.36-5.26). Significant positive trends of home morning, home evening, 24-h, and daytime SBP were observed across quartiles of urinary Na/K ratio (trend P < 0.041; adjusted mean values between Q1 and Q4 of urinary Na/K ratio: 121.0-125.5 mmHg for home morning, 120.1-123.8mmhg for home evening, 121.6-123.4mmHg for 24-h, 127.5-129.5 mmHg for daytime). Urinary Na/K ratio was not significantly associated with office or night-time SBP and nocturnal BP fall (trend P > 0.13). In the model with both home morning or evening SBP and daytime SBP, only home SBP was significantly associated with urinary Na/K ratio (P < 0.048 for home SBP).
These findings suggest that urinary Na/K ratio might be more strongly associated with home BP than with 24-h and daytime BP but was not associated with night-time BP.
PDF
