Serum cystatin C to creatinine ratio is associated with sarcopenia in non-dialysis-dependent chronic kidney disease.

BACKGROUND: Sarcopenia is a prevalent complication in patients with chronic kidney disease and is associated with poor quality of life, morbidity, and mortality. Several candidate biomarkers have been evaluated for this condition. This study assessed the serum cystatin C to creatinine (serum cystatin C/Cr) ratio as a potential biomarker for sarcopenia in patients with non-dialysis-dependent chronic kidney disease. METHODS: This study enrolled 517 outpatients. Muscle mass (lean tissue index) was measured using a bioimpedance spectroscopic device, and muscle strength (handgrip strength) was also measured. Sarcopenia was defined as a combination of low muscle strength and low muscle mass. RESULTS: Sarcopenia was observed in 25.5% of patients, and the mean serum cystatin C/Cr ratio was significantly higher in patients with sarcopenia than in those without it (1.14 ± 0.26 vs. 1.01 ± 0.27, p < 0.001). The prevalence of sarcopenia and low lean tissue index increased as the cystatin C/Cr ratio increased. The negative predictive value of the cystatin C/Cr ratio for sarcopenia or low lean tissue index was ≥80%. Multivariate analyses revealed that when the serum cystatin C/Cr ratio increased by 1, the risk of sarcopenia, low lean tissue index, and low handgrip strength increased by 4.6-, 7.2-, and 2.6-fold, respectively (p = 0.003, p < 0.001, and p = 0.048). The association was maximized in patients with an estimated glomerular filtration rate of <30 mL/min/1.73 m2. CONCLUSION: Calculating the serum cystatin C/Cr ratio could be helpful for detecting and managing sarcopenia in patients with chronic kidney disease.

Late stage 3 chronic kidney disease is an independent risk factor for sarcopenia, but not proteinuria.

Most epidemiologic studies assessing the relationship between chronic kidney disease (CKD) and sarcopenia have been performed in dialysis patients. This study aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR), proteinuria, and sarcopenia in patients with non-dialysis-dependent CKD. A total of 892 outpatients who did not show any rapid changes in renal function were enrolled in this observational cohort study. We measured the muscle mass using bioimpedance analysis and handgrip strength (HGS), and sarcopenia was defined as low HGS and low muscle mass. Sarcopenia was found in 28.1% of the patients and its prevalence decreased as the body mass index (BMI) increased; however, in patients with BMI ≥ 23 kg/m2, the prevalence did not increase with BMI. As eGFR decreased, the lean tissue index and HGS significantly decreased. However, the eGFR did not affect the fat tissue index. The risk of sarcopenia increased approximately 1.6 times in patients with eGFR < 45 mL/min/1.73 m2. However, proteinuria was not associated with sarcopenia. With a decrease in eGFR, the lean muscle mass and muscle strength decreased, and the prevalence of sarcopenia increased. In patients with late stage 3 CKD, further assessment of body composition and screening for sarcopenia may be needed.

Incidence of malignancy and related mortality after kidney transplantation: a nationwide, population-based cohort study in Korea.

Post-transplant malignancy (PTM) is a leading cause of premature mortality among kidney transplantation recipients. However, population-based cohort studies that cover incidence, mortality, and risk factors for PTM are rarely reported, especially in East Asia. We designed a retrospective cohort study using a national population-based database. A total of 9915 kidney recipients between 2003 and 2016 were included. During this period, 598 cases (6.0%) of de novo PTM occurred. The most common PTM was thyroid cancer (14.2%), followed by colorectal (11.2%), kidney (10.7%), and stomach cancers (8.9%). The standardised incidence ratio for all-site cancer was 3.9. The risks of Kaposi sarcoma (192.9) and kidney cancer (21.1) were more than 10 times those of the general population. Cancer-related deaths were 89 (14.9%) with liver cancer being the highest (14.6%), followed by lung cancer (13.5%), non-Hodgkin lymphoma (NHL) (12.4%), stomach cancer (9.0%), and colorectal cancer (7.9%). The standardised mortality ratio (SMR) was slightly elevated (1.4). A notable increase in SMR was observed for lymphoma (9.3 for Hodgkin lymphoma and 5.5 for NHL). Older age and graft failure were significantly related to PTM. These findings reflecting geographical variation have implications for the development of strategies for fatal cancers to prevent premature deaths from PTM.

Role of peribrachial fat as a key determinant of brachial artery dilatation for successful arteriovenous fistula maturation in hemodialysis patients.

The functional quality of the inflow artery is one of the most important determinants of arteriovenous fistula (AVF) success. We evaluated the association of early optimal brachial arterial dilatation with a successful AVF maturation and assessed the role of peribrachial adipose tissue in determining brachial arterial distensibility. All patients underwent a preoperative vascular mapping with Doppler ultrasound (US), and only patients who had suitable vessels for AVF creation were enrolled (n = 162). Peribrachial fat thickness was measured using US. To evaluate the degree of brachial dilatation, follow-up US was performed at 1 month after surgery, and early brachial artery dilation was defined as the change in postoperative arterial diameter compared to the preoperative value. The primary outcome was failure to achieve a clinically functional AVF within 8 weeks. Nonfunctional AVF occurred in 21 (13.0%) patients, and they had a significantly lower brachial dilatation than patients with successful AVF during early period after surgery (0.85 vs. 0.43 mm, p = 0.003). Patients with a brachial dilatation greater than median level showed a 1.8-times higher rate of achieving a successful AVF than those without. Interestingly, the early brachial dilatation showed significant correlations with diabetes (r = -0.260, p = 0.001), peribrachial fat thickness (r = -0.301, p = 0.008), and the presence of brachial artery calcification (r = -0.178, p = 0.036). Even after adjustments for demographic factors, comorbidities, and baseline brachial flow volume, peribrachial fat thickness was an independent determinant for early brachial dilatation (ß = -0.286, p = 0.013). A close interplay between the peri-brachial fat and brachial dilatation can be translated into novel clinical tools to predict successful AVF maturation.

Acute kidney injury can predict in-hospital and long-term mortality in elderly patients undergoing hip fracture surgery.

BACKGROUND: Hip fracture is a common health problem in the elderly that is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication in elderly patients undergoing surgery and is associated with the clinical outcome. We evaluated the incidence and risk factors of AKI in elderly patients undergoing hip fracture surgery and the impact of AKI on short- and long-term clinical outcomes. METHODS: We performed a retrospective cohort study of 450 elderly patients who underwent hip fracture surgery between January 2010 and December 2012. We defined AKI according to the Acute Kidney Injury Network (AKIN) criteria and investigated the effect of AKI on the duration of hospital stay and in-hospital and long-term mortality. RESULTS: Of the 450 patients, 95 (21.1%) developed AKI during hospitalization and 178 (39.6%) died, with a mean follow-up of 3.6 ± 1.0 years. The baseline serum creatinine level, use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, red blood cell transfusion volume, and history of coronary artery disease were independent risk factors for AKI. Patients with AKI during hospitalization had significantly longer hospital stays and higher in-hospital and long-term mortality than those without AKI. Multivariate analysis revealed that age, history of coronary artery disease, serum albumin level, and AKI were independent predictors of long-term mortality. CONCLUSIONS: AKI is a frequent complication in elderly patients undergoing hip fracture surgery and is independently associated with increased in-hospital and long-term mortality.

Leptin, pre-existing vascular disease, and increased arteriovenous fistula maturation failure in dialysis patients.

BACKGROUND: The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients. METHODS: Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima. AVF maturation failure was defined as an AVF that could not be used successfully by the third month after its creation. RESULTS: The prevalence of body mass index ≥30 kg/m2 was 17%, and AVF maturation failure occurred in 28 (45%) patients. Patients within the highest leptin tertile showed significantly higher maturation failure rate, independent of age, gender, diabetes, and body mass index. On histologic examination, significant differences in intimal hyperplasia (13.3 ± 4.5 vs 18.2 ± 5.2 vs 30.3 ± 14.3 µm) and medial thickening (76.8 ± 23.7 vs 103.9 ± 33.6 vs 109.3 ± 36.5 µm) were observed across leptin tertiles. Similarly, medial fibrosis was most severe in the highest tertile. According to the immunohistochemical staining, most intimal cells were α-smooth muscle actin-positive, vimentin-positive, desmin-negative myofibroblasts. However, in the lowest tertile, desmin-positive contractile smooth muscle cells were also frequently observed, suggesting relatively slow phenotypic changes in this group. Furthermore, as leptin tertiles increased, the expression of leptin receptor in the luminal border of intima was significantly decreased. CONCLUSIONS: Obesity-related higher fistula maturation failure rate may be partly mediated by higher leptin level-associated pre-existing vascular diseases in end-stage renal disease patients. Decreased expression of leptin receptor may be related to this association.

Obesity-related decrease in intraoperative blood flow is associated with maturation failure of radiocephalic arteriovenous fistula.

OBJECTIVE: Successful arteriovenous fistula (AVF) maturation is often challenging in obese patients. Optimal initial intraoperative blood flow (IOBF) is essential for adequate AVF maturation. This study was conducted to elucidate the effect of obesity on IOBF and radiocephalic AVF maturation. METHODS: Patients with a newly created radiocephalic AVF were included (N = 252). Obesity was defined as a baseline body mass index (BMI) ≥25 kg/m(2), and primary maturation failure was defined as failure to use the AVF successfully by 3 months after its creation. IOBF was measured immediately after construction of the AVF with a VeriQ system (MediStim, Oslo, Norway). RESULTS: The mean BMI was 24.1 ± 3.9 kg/m(2), and the prevalence of obesity was 31.3%. Particularly, 8.3% (21 patients) had a BMI ≥30 kg/m(2). Primary maturation failure occurred in 100 patients (39.7%), and an IOBF <190 mL/min was closely associated with the risk of maturation failure (relative risk, 3.05; 95% confidence interval, 1.52-6.11). Compared with nonobese patients, obese subjects had a significantly higher prevalence of diabetes and elevated high-sensitivity C-reactive protein levels, whereas diameters of vessels were similar. When the patients were further divided into three groups as BMI <25, 25 to 29.9, and ≥30 kg/m(2), patients in the higher BMI group showed significantly lower IOBF and higher maturation failure rate. According to multivariate analysis, the statistically significant variables that determined maturation failure were obesity, previous vascular disease, increased high-sensitivity C-reactive protein levels, and IOBF <190 mL/min. CONCLUSIONS: Obese patients had a significantly lower IOBF, and both obesity and low IOBF contributed to the primary maturation failure of AVF. Obesity-associated inflammation and atherosclerosis might play roles in this association.

Four-Year Changes in Visceral Fat Mass and the Risk of Developing Proteinuria in the General Population.

BACKGROUND: Previous cross-sectional studies demonstrated the close relationship between visceral obesity and the increased prevalence of proteinuria. But, little is known about the role of changes in visceral fat mass (∆VFM) over several years in the development of proteinuria. In this longitudinal cohort study with the general population, the changes in ∆VFM as well as baseline VFM on proteinuria development were evaluated. METHODS: Healthy individuals (n = 2393) who participated in two health screening exams were analyzed. Subjects were divided into three groups based on gender-specific tertiles of baseline VFM and ∆VFM. Each patient was tested for proteinuria using a dipstick, and proteinuria was defined as 1+ or greater. RESULTS: The mean age was 51.9±7.7 years, and the incidence of proteinuria was 3.9% (n = 93). During the 4 years, 52.5% of the subjects experienced a decline in ∆VFM. However, subjects who developed proteinuria exhibited a significant increase in ∆VFM. Even after adjustment for age, smoking, systolic and diastolic BP, serum creatinine, and hs-CRP levels, the highest tertiles for baseline VFM [men, odds ratio (OR) 3.43, 95% confidence interval (CI) 1.22-9.67; women, OR 2.01, 95% CI 1.05-4.15] and ∆VFM (men, OR 2.92, 95% CI 1.22-6.99; women, OR 3.16, 95% CI 1.56-6.39) were independent predictors of proteinuria development. Following adjustment of both parameters, subjects in the highest baseline VFM and ∆VFM tertiles exhibited the greatest risk of proteinuria development, which suggested the additive harmful effects of the two factors. CONCLUSIONS: Baseline VFM and greater increase in ∆VFM were both important risk factors for developing proteinuria in the general population. Appropriate education and interventions to prevent accumulation of VFM should be the major focus of preemptive strategies.

The association between an abnormal post-voiding urine volume and a lower estimated glomerular filtration rate in patients with type 2 diabetes with no voiding symptoms.

BACKGROUND/AIMS: Diabetic cystopathy is a frequent complication of diabetes mellitus. This study assessed the association between the post-voiding residual (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding symptoms. METHODS: This study investigated 42 patients with type 2 diabetes who were followed regularly at our outpatient clinic between July 1, 2008 and June 30, 2009. No patient had voiding problems or International Prostate Symptom Scores (IPSSs) ≥ 12. An urologist performed the urological evaluations and the PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was considered abnormal, which was the primary study outcome. RESULTS: The mean patient age was 60 ± 10 years; the IPSS score was 3.7 ± 3.3; and the diabetes duration was 11.9 ± 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50 mL. The presence of overt proteinuria or microalbuminuria was associated with an increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a significantly lower estimated glomerular filtration rate (eGFR) compared with those with a PVR ≤ 50 mL (59.2 ± 27.1 mL/min/1.73 m(2) vs. 28.7 ± 23.3 mL/min/1.73 m(2); p < 0.001). Multivariate logistic analysis revealed that a lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04) was a significant risk factor for a PVR > 50 mL. CONCLUSIONS: Patients with diabetic nephropathy had a significantly higher PVR and a lower eGFR was associated with an abnormal PVR.

The prevention of contrast-induced nephropathy by simultaneous hemofiltration during coronary angiographic procedures: a comparison with periprocedural hemofiltration.

BACKGROUND: Periprocedural (6 h pre- and 24 h post-angiography) hemofiltration appears to effectively prevent contrast-induced nephropathy (CIN) in chronic kidney disease (CKD) patients undergoing coronary angiography. However, this procedure over-uses medical resources, and the cessation of hemofiltration during coronary angiography results in persistent renal injury. In comparison, simultaneous hemofiltration performed only during coronary angiography requires fewer medical resources and can provide instantaneous protection against CIN. METHODS: Sixty-eight CKD patients (serum creatinine, 2.51±1.15 mg/dL) undergoing coronary angiography were randomized in a 1:2 ratio to receive either periprocedural (n=23) or simultaneous (n=45) hemofiltration. The expected CIN rate was similar for the two groups (41.3% versus 40.0%, p=0.769). RESULTS: On day 3 after contrast exposure, four and seven patients in the periprocedural and simultaneous groups, respectively experienced CIN (17.4% versus 15.6%, p=0.846). On days 5-30, seven and three patients in the periprocedural and simultaneous groups, respectively experienced CIN (30.4% versus 6.7%, p=0.009). The serum creatinine levels of patients in the periprocedural group transiently decreased on day 1 and persistently increased during days 5-30 compared with the simultaneous group. This difference between the two groups in terms of creatinine levels over time was statistically significant (F statistic=6.830; p=0.001, by ANCOVA). The cost of hemofiltration was doubled in the periprocedural group ($1066±83 versus $504±40, p<0.001). CONCLUSIONS: Simultaneous hemofiltration provide equal early (day 3) and better late-stage (days 5-30) renal protection against CIN at a significantly lower cost compared with periprocedural hemofiltration.

Identification of pancreatic cancer-associated tumor antigen from HSP-enriched tumor lysate-pulsed human dendritic cells.

PURPOSE: Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunity are the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunity than DCs pulsed with conventional tumor lysate (TL), the underlying molecular mechanism is unclear. In order to explore the molecular basis of this approach and to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derived from TL- and HTL-pulsed dendritic cells by mass spectrophotometry. MATERIALS AND METHODS: Human monocyte-derived dendritic cells were pulsed with TL or HTL prior to maturation induction. To delineate differences of MHC-bound peptide repertoire eluted from DCs pulsed with TL or HTL, nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS) was employed. RESULTS: HTL, but not TL, significantly induced DC function, assessed by phenotypic maturation, allostimulation capacity and IFN-γ secretion by stimulated allogeneic T cells. DCs pulsed with TL or HTL displayed pancreas or pancreatic cancer-related peptides in context of MHC class I and II molecules. Some of the identified peptides had not been previously reported as expressed in pancreatic cancer or cancer of other tissue types. CONCLUSION: Our partial lists of MHC-associated peptides revealed the differences between peptide profiles eluted from HTL-and TL-loaded DCs, implying that induced heat shock proteins in HTL chaperone tumor-derived peptides enhanced their delivery to DCs and promoted cross-presentation by DC. These findings may aid in identifying novel tumor antigens or biomarkers and in designing future vaccination strategies.

Association between cardiac valvular calcification and myocardial ischemia in asymptomatic high-risk patients with end-stage renal disease.

OBJECTIVE: Valvular calcification is associated with significant morbidity and mortality in patients with end stage renal disease (ESRD). This study examined the hypothesis that valvular calcification is a marker of myocardial ischemia in asymptomatic high-risk patients with ESRD. METHODS: Echocardiography and myocardial perfusion single-photon emission computed tomography were performed in 285 asymptomatic high-risk patients with ESRD at initiation of dialysis. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS) and defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. The presence of cardiac valvular calcification was assessed by echocardiography and defined as aortic valve calcification or mitral valve calcification. RESULTS: Eighty-five (29.9%) patients had echocardiographic evidence of cardiac valvular calcification. The presence of myocardial ischemia was significantly associated with aortic valve calcification (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.76-5.78; p < 0.001), mitral valve calcification (OR = 3.31; 95% CI = 1.74-6.28; p < 0.001), and cardiac valvular calcification (OR = 3.18; 95% CI = 1.79-5.65; p < 0.001). The presence of moderate to severe myocardial ischemia (SDS ≥ 8) was independently associated with cardiac valvular calcification (OR = 2.86; 95% CI = 1.12-7.27; p = 0.028). CONCLUSION: Valvular calcification was significantly associated with the presence of inducible myocardial ischemia in asymptomatic patients with ESRD, and may be a potential marker of patients at high-risk for the presence of silent myocardial ischemia.

KLOTHO gene polymorphism is associated with coronary artery stenosis but not with coronary calcification in a Korean population.

Experimental studies have demonstrated KLOTHO gene polymorphism might be associated with vascular atherosclerosis and calcification. However, the impact of this genetic variant on human coronary arteries still remains to be elucidated. We investigated the effect of a KLOTHO gene variant on coronary artery stenosis and calcification. Four hundred and thirty-four patients referred for chest pain were enrolled. All the patients underwent coronary angiography and were investigated for polymorphism of the KLOTHO G395A gene. Coronary artery disease (CAD) was defined as > or = 50% diameter stenosis in at least one coronary artery. The other patients were considered to be controls. Homozygotes or heterozygotes for G395A were significantly more common in the CAD patients than in the controls (30.2% versus 21.5%, P = 0.039). In the subgroup aged < 60 years, the G395A mutant was more frequent in CAD than in control (35.3% versus 18.8%, P = 0.016), but in patients > or = 60 years, there was no difference (28.0% versus 24.1%, P = 0.473). Using multivariate analysis, we identified the KLOTHO gene G395A mutant as an independent risk factor of CAD (OR 1.712, 95% CI [1.066-2.749], P = 0.026). The frequency of the KLOTHO gene G395A mutant was not different between the calcified and noncalcified coronary artery groups (25.7%, 26.4%, respectively, P = 0.861) and an A allele carrier state was not an independent risk factor of coronary artery calcification. In conclusion, the KLOTHO gene G395A allele carrier state may be associated with CAD but not with coronary artery calcification in this Korean population.