Chung-Jen Yen

Effects of age and diabetes on blood flow rate and primary outcome of newly created hemodialysis arteriovenous fistulas

To study the feasibility of creating a radiocephalic hemodialysis fistula in elderly and diabetic patients, we prospectively studied 176 patients undergoing the first permanent vascular access creation and followed the outcome of fistula until primary failure or success was assessed. Color duplex ultrasonography was used to measure the blood flow rate. Fistula blood flow rate was significantly smaller in elderly patients, however, it was >400 ml/min in over 78% of the elderly patients with successful fistulas. There was no difference in fistula blood flow rate between nondiabetics and diabetics. Dialysis adequacy (Kt/V) via fistula was the same between age groups and between diabetes mellitus status. Old age or diabetes per se did not significantly predispose a new fistula to primary failure, but concurrent old age and diabetes markedly increase the risk. In conclusion, a good primary outcome of newly created radiocephalic fistula and adequate dialysis via fistula were demonstrated for elderly and diabetic patients. However, the longevity of fistula in elderly and diabetic patients needs further study.

Metabolic Syndrome and Insulin Resistance as Risk Factors for Development of Chronic Kidney Disease and Rapid Decline in Renal Function in Elderly

CONTEXT Studies addressing the association of metabolic syndrome and insulin resistance with the risks of incident chronic kidney disease (CKD) and the progression of renal function were either lacking or inconclusive. OBJECTIVE The aim of this study was to define the effect of metabolic syndrome and insulin resistance on the development of new CKD and the decline in renal function. DESIGN AND SETTING A prospective cohort study was conducted at a tertiary university-based hospital in Taiwan. PATIENTS AND OTHER PARTICIPANTS We studied a total of 1456 Asians 65 or older who were followed for an average of 3.15 yr. Within the cohort, we measured insulin resistance using the homeostasis model assessment formula in 652 nondiabetic participants. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES We measured the prevalence and incidence of CKD and the annual decline of the estimated glomerular filtration rate. RESULTS We found that the adjusted odds ratio for prevalent CKD in association with metabolic syndrome was 1.778 (95% confidence interval, 1.188 to 2.465), the hazard ratio for rapid decline in renal function was 1.042 (0.802-1.355), and the hazard ratio for incident CKD was 1.931 (1.175-3.174). With each one-unit increment of insulin resistance, the odds ratio of prevalent CKD and proteinuria were raised 1.312-fold (1.114 to 1.545) and 1.278-fold (1.098 to 1.488), respectively. Insulin resistance was not associated with incident CKD. Increment of insulin resistance per unit was associated with 1.16-fold (1.06 to 1.26) elevation in the hazard ratios of the decline in renal function. CONCLUSIONS Metabolic syndrome predicts the risks of prevalent and incident CKD, whereas insulin resistance is associated with prevalent CKD and rapid decline in renal function in elderly individuals.

Age-Associated Changes in Interferon-γ and Interleukin-4 Secretion by Purified Human CD4+ and CD8+ T Cells

Aging is associated with a decline in immune function. Interferon-γ (IFN-γ) and interleukin-4 (IL-4), two important immune deviation-related cytokines, are mainly produced by type 1 and type 2 T cells, respectively. To investigate the age-associated changes in the secretion of these two cytokines, 20 elderly and 20 young subjects fulfilling the SENIEUR protocol were enrolled. The ratios of CD4+ to CD8+ T cells were not different between the two age groups. The CD4+ and CD8+ T cells were purified by a magnetic cell sorting system, and then activated by concurrent anti-CD3 and anti-CD28 stimulation. The released cytokines were determined by ELISA. Both the CD4+ and the CD8+ T cells of the elderly individuals secreted a significantly larger amount of IFN-γ after activation. Profound IL-4 production by CD8+ T cells was observed in the older subjects compared with that of the young subjects. These data suggested that age-associated decrease in immunity may be related to an imbalance in the secretion of immune deviation cytokines. The number of IL-4-secreting CD8+ T cells (T cytotoxic 2) rose significantly in the older individuals. Our design also provided a useful way to differentiate the T cell subsets secreting the same cytokine, such as IFN-γ-producing T helper 1 and T cytotoxic 1 cells.

Lean Body Mass Predicts Long-Term Survival in Chinese Patients on Peritoneal Dialysis

Background Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients’ outcomes and the factors related to increasing LBM are seldom reported. Methods We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan–Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05) and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05). Group 1 patients also had shorter overall survival and technique survival (p<0.01). Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI). Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. Conclusions LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

Effect of intraperitoneally administered agents on human peritoneal mesothelial cell growth.

During continuous ambulatory peritoneal dialysis, the peritoneal mesothelial cell layer is under continuous sloughing and regeneration processes. Agents unfavorable for mesothelial cell growth may be harmful to the peritoneal membrane. We investigated whether frequent intraperitoneally instilled agents affect mesothelial cell growth. Peritoneal mesothelial cells were cultured from the human omentum. The proliferation was assessed by using a modified methyltetrazolium assay and confirmed by Coulter cell counting. The results showed that a high-glucose medium and heparin inhibited mesothelial cell growth. Cephalothin at the usual intraperitoneal loading and maintenance doses is toxic to mesothelial cells. Ceftazidime is toxic to mesothelial cells at its loading dose and inhibits growth at its maintenance dose. Aminoglycosides including netilmicin, gentamicin, and amikacin all had inhibitory effects at the loading and maintenance dose ranges. Vancomycin had no effect. The usual combinations of heparin and cephalothin with netilmicin or gentamicin as the initial treatment regimen for bacterial peritonitis are toxic to mesothelial cells. These results suggest that some intraperitoneal agents potentially may hamper mesothelial cell regeneration. The judicious use of heparin and the proper choice of antibiotic combinations may be warranted from the point of view of peritoneal protection.

Hyperuricemia associated with rapid renal function decline in elderly Taiwanese subjects.

BACKGROUND/PURPOSE Hyperuricemia is encountered frequently in patients with chronic kidney disease (CKD). We tested the hypothesis that uric acid influences glomerular filtration rate (GFR) and is associated with renal function decline in elderly Taiwanese subjects. METHODS We enrolled 800 elderly Taiwanese subjects for a health checkup. Estimated GFR (eGFR) was measured using the Modification of Diet in Renal Disease Study equation. eGFR < 60 mL/min/1.73 m2 was used to analyze the prevalence and incidence of CKD. Significant renal function decline was defined as a decrease in eGFR of > or = 3 mL/min/1.73 m2 per year. RESULTS The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid level was 6.6 mg/dL in male and 5.6 mg/dL in female subjects, and eGFR was 71.7 mL/min/1.73 m2. Uric acid levels were associated independently and negatively with eGFR after adjusting for conventional factors of renal function decline. One hundred and sixty-two individuals (31.2%) had a significant decline in renal function. As uric acid level increased by 1 mg/dL, the odds of a significant eGFR decline increased by 1.208. CONCLUSION Serum uric acid level was associated with eGFR and decline in renal function in elderly Taiwanese subjects. Whether hypouricemic therapy could retard the progression of CKD deserves further in-depth study.

Glycosylated Hemoglobin and Albumin-Corrected Fructosamine Are Good Indicators for Glycemic Control in Peritoneal Dialysis Patients

Purpose Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients. Methods A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels. Results There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P<0.05), AlbF (r = 0.54, P<0.01), and HbA1c (r = 0.51, P<0.01). The ISF glucose levels in glucose-containing dialysate increased from approximately 7–8 mg/dL within 1 hour of exchange in contrast to icodextrin dialysate which kept ISF glucose levels unchanged. Conclusion HbA1c and AlbF significantly correlated with the mean ISF glucose levels, indicating that they are reliable indices of glycemic control in DM PD patients. Icodextrin dialysate seems to have a favorable glycemic control effect when compared to the other glucose-containing dialysates.

Fibrin-Induced Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells as a Mechanism of Peritoneal Fibrosis: Effects of Pentoxifylline

Excessive fibrin deposition in the peritoneum is thought to be involved in the development of encapsulating peritoneal sclerosis (EPS), an important cause of morbidity and mortality in peritoneal dialysis patients. We investigated fibrin-induced epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) as a possible mechanism of fibrin involvement in EPS. In vitro, fibrin overlay of PMCs altered their morphology; increased α-smooth muscle actin, fibronectin, fibroblast specific protein-1, and αvβ3 integrin expression; and decreased cytokeratin 18 and E-cadherin expression. Fibrin overlay also increased focal adhesion kinase and Src kinase phosphorylation. Fibrin-induced changes were inhibited by treating the cells with αvβ3 integrin antibody or pentoxifylline (PTX). In a rat model, intraperitoneal injection of Staphylococcus aureus and fibrinogen induced severe EPS features, which were attenuated by PTX treatment. PTX-treated rats also showed preserved peritoneal ultrafiltration function and lower concentrations of cytokines than the untreated rats. S. aureus- and fibrinogen-injected rats had higher percentage of cytokeratin-positive cells in the omentum fibrotic tissue than controls; this was also reduced by PTX treatment. Our results suggest that fibrin induces EMT of PMCs by engaging αvβ3 integrin and activating associated kinases. Our EPS animal model showed that fibrin-induced EMT was involved in the pathogenesis of peritoneal fibrosis and was inhibited by PTX.

Prevalence of geriatric conditions: A hospital-wide survey of 455 geriatric inpatients in a tertiary medical center

The aim of this study was to investigate the prevalence of common geriatric conditions in a tertiary medical center. We conducted a cross-sectional, hospital-wide survey of 455 inpatients, aged 65 and older, from 24 medical and surgical units of a 2200-bed urban academic medical center in Taiwan. Patients were screened in face-to-face interviews for 15 geriatric conditions. The prevalence of geriatric conditions was determined and compared by medical versus surgical services. Our sample of participants had a mean age of 75.3±6.1 years (±S.D.), range=65-92. The prevalence of geriatric conditions ranged from 5% (pressure ulcers) to 57% (polypharmacy; taking>5 prescriptions). The majority was visually impaired (74%) and complained of sleep disturbance during their hospital stay (58%). Prevalence rates of certain geriatric conditions differed significantly between medical and surgical units, suggesting that care should address not only common conditions but also those with higher rates on different units. Furthermore, high rates of geriatric conditions indicate strong needs for care that does not fit into traditional disease models of medicine. Care should be better targeted to address different risks for geriatric conditions of medical versus surgical geriatric inpatients in acute care settings.

Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.