Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients.

BACKGROUND: The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. METHODS: We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. RESULTS: A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). CONCLUSION: We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

Relative handgrip strength as a marker of metabolic syndrome: the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015).

Purpose: Muscles play an important role in energy metabolism. Several studies have investigated the association between muscle mass and metabolic syndrome (MetS), reporting conflicting results. However, studies concerning the association between muscle strength and MetS are limited. We aimed to investigate the association between relative handgrip strength (HGS) and MetS in Korean adults. Participants and methods: We analyzed data from 5,014 Korean adults aged ≥20 years (2,472 men and 2,542 women) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015). Results: The increasing quartiles of relative HGS (defined as the sum of both hands' HGS divided by body mass index) were inversely associated with the risk of MetS in both men and women (OR, 0.37; 95% CI, 0.30-0.45, vs OR, 0.19; 95% CI, 0.14-0.27, respectively) after multivariable adjustment for age, region of residence, smoking status, heavy alcohol consumption, regular exercise, family income, and education level. On multivariable logistic regression analyses, participants with the highest relative HGS had a significant decrease in relative risk of MetS, compared with those with the lowest relative HGS. The multivariable-adjusted ORs (with 95% CIs) for MetS in quartiles 1, 2, 3, and 4 were 1.00, 0.72 (0.55-0.94), 0.34 (0.26-0.46), and 0.22 (0.15-0.32) in men and 1.00, 0.50 (0.36-0.68), 0.26 (0.17-0.40), and 0.16 (0.09-0.27) in women, respectively. Conclusion: Relative HGS showed a highly significant inverse association with the risk of MetS in Korean adults, and it can be a novel biomarker for assessing the risk of MetS.

Association between serum cystatin C and bone mineral density in Korean adults.

Background: Serum cystatin C has been known as a novel marker of preclinical renal dysfunction, and higher cystatin C levels are associated with increased risks of hip and nonvertebral fractures. However, there are few reports on the association between serum cystatin C and bone mineral density (BMD), especially in the Asian population. We evaluated the association between cystatin C levels and BMD of the spine and hip in Korean adults. Methods: A cross-sectional study was performed in 865 Korean adults (325 men and 540 women) who participated in a comprehensive medical examination program and underwent bone densitometry. Renal function was assessed by the estimated glomerular filtration rate (eGFR), which was calculated using an equation based on creatinine (eGFRcre) and cystatin C (eGFRcys). Results: The serum cystatin C level was negatively correlated with different types of BMD, including the lowest lumbar, total lumbar, femoral neck, and total femur BMD, in women, but not in men. Higher cystatin C levels were associated with a higher prevalence of osteoporosis in women (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.69-8.03; P=0.001), but not in men (OR, 0.85; 95% CI, 0.30-2.38; P=0.761). However, this association was attenuated in the multivariable model adjusted for age, body mass index, serum 25-hydroxyvitamin D3, and creatinine (OR, 1.01; 95% CI, 0.38-2.71) in women. In addition, the eGFRcys showed a stronger positive correlation with BMD than the eGFRcre. Conclusion: Our findings suggest that serum cystatin C levels might help identify women with osteoporosis who are susceptible to fractures.

A case of incidentally discovered subclinical cushing syndrome in a patient with chronic fatigue and anxiety.

Subclinical Cushing syndrome (SCS) is a hypothalamic-pituitary-adrenal axis abnormality characterized by autonomous cortisol secretion in patients with no typical signs or symptoms of Cushing syndrome. SCS patients may have adverse metabolic and cardiovascular effects due to slight, but continuous glucocorticoid secretion. Glucocorticoids also affect behavior, mood, neural activity, and a number of specific biochemical processes in the central nervous system. Here, we report a case of SCS due to an adrenal incidentaloma in a hypertensive diabetic patient who presented with chronic fatigue and anxiety that disappeared after the removal of the adrenal adenoma.