Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients.

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.1 mL/min/1.73 m(2), mean age 70.3 ± 10.1 years). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) and CAC score, and this relationship was investigated. Among the subjects, AAC was present in 109 patients (86.5 %) as defined by ACI >0 and median ACI was 11.7 %. ACI increased in accordance with advances in CAC score grades (3.0, 5.2, 17.2, and 32.8 % for CAC score 0, 1-100, 101-400, and 401 or more, respectively, p < 0.001). Even after multivariate adjustment, ACI was independently associated with severe CAC score as defined by CAC score >400 [odds ratio 1.08, 95 % confidence interval (CI) 1.04-1.12, p < 0.001]. Receiver-operating curve analysis showed that the ACI optimal cut-off value predicting severe CAC score was 16.5 % (area under the curve = 0.79, 95 % CI 0.69-0.90, p < 0.001). The C statics for predicting CAC score was significantly increased by adding ACI values to the model including other risk factors (0.853 versus 0.737, p = 0.023). In conclusion, the ACI value of 16.5 % allows us to predict the presence of severe CAC in CKD patients, and that the addition of ACI to the model with traditional risk factors significantly improves the predictive ability of severe CAC score. These data reinforce the utility of ACI as a screening tool in clinical practice.

Association of Estimated Glomerular Filtration Rate and Proteinuria With Lipid-Rich Plaque in Coronary Artery Disease.

BACKGROUND: Estimated glomerular filtration rate (eGFR) and proteinuria are both important determinants of the risk of cardiovascular disease and mortality. The aim of the present study was to investigate the independent and combined effects of eGFR and proteinuria on tissue characterization of the coronary plaques of culprit lesions. METHODS AND RESULTS: Conventional intravascular ultrasound and 3-D integrated backscatter intravascular ultrasound (IB-IVUS) were performed in 555 patients undergoing elective percutaneous coronary intervention. They were divided into 2 groups according to the absence or presence of proteinuria (dipstick result ≥1+). Patients with proteinuria had coronary plaque with significantly greater percentage lipid volume compared with those without (43.6±14.8% vs. 48.6±16.1%, P=0.005). Combined analysis was done using eGFR and absence or presence of proteinuria. Subjects with eGFR 45-59 ml/min/1.73 m2 and proteinuria were significantly more likely to have higher percent lipid volume compared with those with eGFR >60 ml/min/1.73 m2 without proteinuria. After multivariate adjustment for confounders, the presence of proteinuria proved to be an independent predictor for lipid-rich plaque (OR, 1.85; 95% CI: 1.12-3.06, P=0.016). CONCLUSIONS: The addition of proteinuria to eGFR level may be of value in the risk stratification of patients with coronary artery disease.

Renal function evaluation in patients with cancer who were scheduled to receive carboplatin or S-1.

BACKGROUND: Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney. Serum cystatin-C (sCys-C) is a GFR marker with little affected by body muscle mass volume. And GFR equations based on serum creatinine (eGFRcreat) and sCys-C (eGFRcys) were developed; however, accuracy of eGFRcys has not been elucidated fully among patients with cancer. Therefore, we analyzed the performance of GFR equations among patients with cancer whose GFR values were measured by inulin clearance (Cin). METHODS: Study design was a cross-sectional study. Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients. Correlation with Cin and slope of regression line were evaluated in eGFRcreat and eGFRcys. Single and multiple regression analyses were analyzed to identify associating factors with eGFRcreat/Cin or eGFRcys/Cin. RESULTS: Age, body weight, body mass index (BMI) and sCr were different between cancer patients and non-cancer patients, but sCys-C and Cin were consistent in 2 groups. The slope of the regression line for Cin vs. eGFRcys with zero intercept in cancer patients was 1.10 (95 % CI: 1.02-1.17), which was significantly different from 1.0. In multiple regression analysis revealed that BMI and urinary creatinine excretion were significantly associated with eGFRcreat/Cin, and cancer was only associating factor with eGFRcys/Cin. CONCLUSION: eGFRcys should not be used for evaluation of renal function in patients with cancer because it underestimates GFR.

Validation of the equations for estimating daily sodium excretion from spot urine in patients with chronic kidney disease.

BACKGROUND: Measuring sodium excretion in a 24-h urine collection is the most reliable method of estimating salt intake, but it is not applicable to all patients. As an alternative, equations for estimating Na excretion from Japanese by a spot urine sample were created, but they have not been validated in patients with chronic kidney disease (CKD), which are frequently associated with nocturia and medication. METHODS: We enrolled 136 patients with CKD and collected both 24-h urine and the first morning urine. Na excretion was estimated from the first morning urine by Kawasaki's equation, which was originally used for the second morning urine, and Tanaka's equation, which is applied for spot urine samples taken at any time from 9 am to 7 pm. We evaluated the two equations for bias, RMSE and accuracy within 30 and 50% of the measured Na excretion. RESULTS: Bias, RMSE and accuracy within 30% of the estimated Na excretion were 48 ± 69 and 2 ± 69 mmol/day, 84 and 69 mmol/day, and 35 and 49% using Kawasaki's equation and Tanaka's equation, respectively. Na excretion in the first morning urine was accurately estimated by Tanaka's equation, but it was overestimated by Kawasaki's equation. Nocturia and medication such as diuretics and ACE inhibitor or angiotensin receptor blocker did not affect the accuracy with which Na excretion was estimated by Tanaka's equation substantially. CONCLUSION: Tanaka's equation for estimating Na excretion from the first morning urine in patients with CKD is accurate enough for use in clinical practice.

Impact of abdominal aortic calcification on long-term cardiovascular outcomes in patients with chronic kidney disease.

BACKGROUND: The presence of abdominal aortic calcification (AAC) can predict cardiovascular (CV) outcomes in hemodialysis patients. However, little is known about the predictive value of AAC for CV outcomes in chronic kidney disease (CKD) patients without hemodialysis. The aim of this study was to investigate the prevalence and the predictive value of AAC in asymptomatic CKD patients. METHODS: We prospectively evaluated 347 asymptomatic CKD patients without hemodialysis [median estimated glomerular filtration rate (eGFR): 43.2 mL/min/1.73 m(2)]. A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) as a semi-quantitative measure of AAC. The patients were divided into three groups according to the tertiles of ACI. RESULTS: Among the subjects, AAC was found (ACI > 0) in 296 patients (86.3%), and the median ACI was 11.4%. During the median follow-up of 41.5 months, a total of 33 CV events were observed. Patients with the highest tertile of ACI had the highest risk of CV outcomes compared with the other two groups (96.5%, 93.0%, and 74.3%, respectively; p < 0.001). The Cox proportional hazard models showed that ACI was an independent predictor of CV outcomes (hazard ratio 1.36, 95% confidence interval 1.17-1.60, p < 0.001). The C-index was also significantly increased by adding eGFR and ACI values to the model along with the other conventional risk factors (0.79 versus 0.66, p = 0.043). CONCLUSION: Evaluation of the AAC provides useful information for predicting adverse clinical outcomes among asymptomatic CKD patients without hemodialysis.

Genome diversification mechanism of rodent and Lagomorpha chemokine genes.

Chemokines are a large family of small cytokines that are involved in host defence and body homeostasis through recruitment of cells expressing their receptors. Their genes are known to undergo rapid evolution. Therefore, the number and content of chemokine genes can be quite diverse among the different species, making the orthologous relationships often ambiguous even between closely related species. Given that rodents and rabbit are useful experimental models in medicine and drug development, we have deduced the chemokine genes from the genome sequences of several rodent species and rabbit and compared them with those of human and mouse to determine the orthologous relationships. The interspecies differences should be taken into consideration when experimental results from animal models are extrapolated into humans. The chemokine gene lists and their orthologous relationships presented here will be useful for studies using these animal models. Our analysis also enables us to reconstruct possible gene duplication processes that generated the different sets of chemokine genes in these species.

Osteoclast-forming suppressive compounds from Makomotake, Zizania latifolia infected with Ustilago esculenta.

A novel compound (1) and a known one (2) were isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta, as osteoclast-forming suppressive substances.