Association between body mass index and chronic kidney disease: A population-based, cross-sectional study of a Japanese community

Chronic kidney disease (CKD) has recently been recognized as a risk factor for cardiovascular disease, while the mechanism by which CKD develops remained to be clarified. In the present study, we conducted a cross-sectional, community-based study to identify the factor(s) associated with CKD. We examined 1978 local residents of the Kiyotake area of Japan (697 males and 1281 females; age, 60.8 ± 11.0 years; mean ± SD), who had an annual health check-up. Diagnosis of CKD was made based on dipstick proteinuria of +1 or higher, or on a reduced glomerular filtration rate (GFR) estimated from serum creatinine level to less than 60 ml/min/1.73 m2. Body mass index (BMI) and prevalence of obesity in the residents with CKD were found to be higher than in those without CKD in both genders. When compared with the residents without CKD, the ratios of residents taking antihypertensive medicines were higher in both genders, and the blood pressure and fasting blood glucose levels of males and the triglyceride level of females were elevated in those with CKD. These parameters or factors were found to be significant for CKD by a univariate logistic analysis. We further analyzed the data with a multivariate logistic method using age, BMI, antihypertensive and antidyslipidemic medicines, blood pressure, serum lipid and glucose as independent covariates, and found that BMI was a significant parameter independently correlated with CKD in both genders. Thus, increased BMI is associated with CKD independently of blood pressure, serum lipid and glucose levels in the general population

Purification and characterization of PAMP-12 (PAMP[9–20]) in porcine adrenal medulla as a major endogenous biologically active peptide

AbstractProadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9–20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings

Cardiac Peptides—Current Physiology, Pathophysiology, Biochemistry, Molecular Biology, and Clinical Application

The heart has long been considered a pumping organ, consisting of muscles [...

Gender difference in relationship between body mass index and development of chronic kidney disease

BACKGROUND: An epidemiological approach to preventing the development or progression of chronic kidney disease (CKD) is necessary, while few effective preventive measures are currently available. We conducted a community-based, cohort study to identify the factors associated with the development of CKD in the general population. METHODS: We examined 1876 local residents of a Japanese community who had an annual health check-up and, of those, 1506 residents judged not to have CKD (473 men and 1033 women) were followed for the development of CKD over 10 years. RESULTS: The numbers of male and female residents who developed CKD during the follow-up period were 167 (35.3%) and 299 (28.9%), respectively. As compared to those without CKD development, the residents who developed CKD were older, and had a higher body mass index (BMI), systolic blood pressure, and creatinine in both genders. The rate of CKD development in obese female residents was higher than in non-obese women, but such a difference was not noted in male residents. In addition to age and serum creatinine, we identified BMI as an independently significant factor for the development of CKD in women, but not in men. CONCLUSIONS: Increased BMI is a significant risk factor for the development of CKD in women, and there seems to be a gender difference in the association between increased BMI and the development of CKD in the general population