Quantification of cardiac pumping mechanics in rats by using the elastance-resistance model based solely on the measured left ventricular pressure and cardiac output.

The cardiac pumping mechanics can be characterized by both the maximal systolic elastance (Emax) and theoretical maximum flow (Qmax), which are generated using an elastance-resistance model. The signals required to fit the elastance-resistance model are the simultaneously recorded left ventricular (LV) pressure and aortic flow (Qm), followed by the isovolumic LV pressure. In this study, we evaluated a single-beat estimation technique for determining the Emax and Qmax by using the elastance-resistance model based solely on the measured LV pressure and cardiac output. The isovolumic LV pressure was estimated from the measured LV pressure by using a non-linear least-squares approximation technique. The measured Qm was approximated by an unknown triangular flow (Qtri), which was generated by using a fourth-order derivative of the LV pressure. The Qtri scale was calibrated using the cardiac output. Values of EmaxtriQ and QmaxtriQ obtained using Qtri were compared with those of EmaxmQ and QmaxmQ obtained from the measured Qm. Healthy rats and rats with chronic kidney disease or diabetes mellitus were examined. We found that the LV Emax and Qmax can be approximately calculated using the assumed Qtri, and they strongly correlated with the corresponding values derived from Qm (P < 0.0001; n = 78): EmaxtriQ = 51.9133 + 0.8992 × EmaxmQ (r2 = 0.8257; P < 0.0001); QmaxtriQ = 2.4053 + 0.9767 × QmaxmQ (r2 = 0.7798; P < 0.0001). Our findings suggest that the proposed technique can be a useful tool for determining Emax and Qmax by using a single LV pressure pulse together with cardiac output.

The relationship of anti-phospholipase A2 receptor antibody and C5a complement with disease activity and short-term outcome in idiopathic membranous nephropathy.

BACKGROUND: The binding of anti-phospholipase A2 receptor (anti-PLA2R) antibody to podocyte and complement activation is the mechanisms of idiopathic membranous nephropathy (IMN). C5a, a complement activation end product, is a strong inflammatory cell stimulator and can influence the behavior of T cells and dendritic cells. This study examined the etiology-disease relationship and significance of auto-antibody and C5a with short-term remission. METHOD: Plasma anti-PLA2R antibody and C5a were measured with the blood samples that were collected when patients were admitted for renal biopsy. The deposition of IgA, IgG, IgM, C1q and C3c in glomerulus was graded according to immunofluorescence staining. The relationship of anti-PLA2R antibody with C5a, glomerular immunoglobulin and complement deposition was examined. Antibody and C5a levels as predictors of short-term remission were also examined. RESULTS: In 72 IMN patients, 50 patients had positive plasma anti-PLA2R antibody. The antibody had positive correlation to proteinuria. Patients with high grade IgG or C3c, but not IgA/IgM/C1q, deposition had higher anti-PLA2R antibody titers. C5a was increased in IMN patients, but had no correlation with anti-PLA2R antibody or proteinuria. The analysis revealed that C5a, not initial anti-PLA2R antibody, was a predictor associated with 12-month remission in patients receiving immunosuppression with multivariate-adjusted OR 0.74 (95% CI, 0.58-0.94, P = 0.01). CONCLUSION: This study provides indirect evidences of etiology-disease relationship of anti-PLA2R antibody in IMN patients. The role of C5a, a predictor of remission, in the disease course of MN and the influences on inflammatory cells in MN patients is worth to be clarified.

Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients.

BACKGROUND: Fetuin-A is known as a circulating inhibitor of vascular calcification. Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients is still uncertain. METHODS: In the post-hoc study, we analyzed serum fetuin-A and biochemical factors (Ca, P, i-PTH, hsCRP, TG, LDL-C) in 50 hemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. 23 patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After the 48-week treatment, the sevelamer group had less serum calcium increment, less iPTH decrement, more ALK-P increment, more hsCRP decrement and more LDL-C decrement. There was no significant difference in the serum fetuin-A decrement between two groups. Decreased serum fetuin-A levels were found after 48-week treatment in both groups: from 210.61 (104.73) to 153.85 (38.64) ug/dl, P = 0.003 in sevelamer group, from 203.95 (107.87) to 170.90 (58.02) ug/mL, P =0.002 in calcium group. The decrement in serum fetuin-A (Δfetuin-A) levels was associated with ΔCa (ρ = - 0.230, P = 0.040), ΔiPTH (ρ = 0.306, P = 0.031) and Δalbumin (ρ = 0.408, P = 0.003), not associated with sevelamer use, ΔP and ΔhsCRP. CONCLUSION: After long-term sevelamer or calcium carbonate treatment, both groups of maintenance HD patients had lower serum fetuin-A levels. Serum levels of increased calcium, decreased iPTH and decreased albumin were associated with the serum fetuin-A decrement.

Repeated cycles of high-dose intravenous immunoglobulin and plasmapheresis for treatment of late antibody-mediated rejection of renal transplants.

BACKGROUND/PURPOSE: Intravenous immunoglobulin (IVIG) plays a central role in the treatment of antibody-mediated rejection (AMR) of renal allografts, but the treatment outcomes for late AMR (>6 months after transplantation) are poor. METHODS: We performed a retrospective study to assess the response patterns of IVIG-based (2 g/kg) desensitization for late AMR. Patients who received desensitization after the pathological diagnosis of late AMR positive for complement component C4d were grouped as the Desensitized Group and compared to a historical Control Group with complement component C4d positivity in retrospective stainings. RESULTS: The 10-year graft survival of the Desensitized Group (73.9%, n = 35) was significantly better than that of the historical Control Group (35.0%, n = 40) without desensitization. In the Desensitized Group, a subgroup of patients (D2 Subgroup, n = 11), who responded to desensitization initially but deteriorated later, was identified to benefit from repeated cycles of desensitization at 31.1 ± 20.9 months. Patients receiving only one cycle of desensitization were further grouped into D1-good (n = 10) and D1-poor (n = 14) based on their long-term renal function. The D2 Subgroup patients did not exhibit significant improvements in renal function compared to the D1-poor patients, until 30 months after IVIG-based desensitization, suggesting desensitization therapy has a working window of approximately 24 months. CONCLUSION: Repeated cycles of IVIG-based desensitization help stabilize long-term renal function in patients with persistent AMR.

B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis.

BACKGROUND/PURPOSE: The effect of rituximab on B cell and immunoglobulin production after therapeutic apheresis has not been studied in ABO-incompatible renal transplant patients. METHODS: Twenty consecutive ABO-incompatible renal transplant patients receiving rituximab induction and double filtration plasmapheresis were enrolled; one case was excluded because of repeated plasmapheresis and immunoglobulin therapy (Incompatible group). The B cell count of the Incompatible group was compared to another group of 18 ABO-compatible renal transplant patients who were operated on during the same period (Compatible group). In the Incompatible group, the total IgM, IgG, and IgG1-4 subclasses after transplantation were compared to those before desensitization. Tacrolimus, mycophenolate mofetil, and steroids were used for both groups. RESULTS: The B cell count of the Incompatible group was significantly lower than the Compatible group post-transplant from Month 1 to Month 11 only. The B cell count of the Compatible group also decreased for the first 6 months, suggesting that maintenance immunosuppressive agents suppress B cells. Total IgG and IgM levels after transplantation were significantly lower than before desensitization during the 24-month follow-up period. The post-transplant IgG3 level was significantly lower than before desensitization for only 3 months. CONCLUSION: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

Pyridoxamine protects against mechanical defects in cardiac ageing in rats: studies on load dependence of myocardial relaxation.

Our team demonstrated in the past that pyridoxamine attenuated arterial stiffening by targeting the pathogenic formation of glycated collagen cross-links in aged rats. Herein, we examined whether pyridoxamine therapy can protect against mechanical defects in myocardial relaxation by improving arterial wave properties and cardiac contractile performance in senescent animals. Fifteen-month-old male Fisher 344 rats were treated daily with pyridoxamine (1 g l(-1) in drinking water) for 5 months and compared with age-matched untreated control animals (20 months old). Arterial wave properties were characterized by wave transit time (τw) and wave reflection factor (Rf). We measured the contractile status of the myocardium in an intact heart as the left ventricular (LV) end-systolic elastance (Ees). Myocardial relaxation was described according to the time constant of the LV isovolumic pressure decay (τe). Pyridoxamine therapy prevented the age-associated prolongation in LV τe and the diminished Ees in senescent rats. The drug also attenuated the age-related augmentation in afterload imposed on the heart, as evidenced by the increased τw and decreased Rf. We found that the LV τe was significantly influenced by both the arterial τw and Rf (τe = 16.3902 + 8.3123 × Rf - 0.4739 × τw; r = 0.7048, P < 0.005). In the meantime, the LV τe and the LV Ees showed a significant inverse linear correlation (τe = 13.9807 - 0.0068 × Ees; r = 0.6451, P < 0.0005). All these findings suggested that long-term treatment with pyridoxamine might ameliorate myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor in aged rats.

Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients.

AIMS: Fibroblast growth factor 23 (FGF23) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients. Sevelamer has been shown to reduce progression of vascular calcification. This study aimed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis (HD) patients. METHODS: In the post-hoc analysis, we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH, hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. Twenty-three patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.82 ± 0.78 to 1.65 ± 0.53 mmol/L, P = 0.000), lower FGF23 (from 2465.97 (2568.88) to 795.61 (1098.39), P = 0.000) and higher s-Klotho levels (from 189.35 (161.88) to 252.94 (517.80) pg/mL, P = 0.000). In calcium carbonate group, there were no significant changes of LDL-C and FGF23, but with a borderline significant increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P = 0.054). Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment (ß = -0.277, P = 0.005), change of serum phosphate (ß = 0.609, P = 0.000) and calcium levels (ß = 0.635, P = 0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (ß = 0.490, P = 0.019). CONCLUSION: Maintenance HD patients had lower serum FGF23 levels, accompanied with significantly increased serum Klotho levels, after 48-week sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the change of serum phosphate and calcium levels. The serum Klotho increment was proportional to the phosphate-lowering power of the binders.

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury.

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients.

Effects of olmesartan on arterial stiffness in rats with chronic renal failure.

BACKGROUND: It has been suggested that the antioxidant properties of olmesartan (OLM), an angiotensin II type 1 receptor (AT(1)R) blocker, contribute to renal protection rather than blood pressure lowering effects despite the fact that causal relationships between hypertension and renal artery disease exist. This study aimed to examine the hypothesis whether the antioxidative activities of OLM were correlated to arterial stiffness, reactive oxygen species and advanced glycation end products (AGEs) formation in rats with chronic renal failure (CRF). METHODS: CRF rats were induced by 5/6 nephrectomy and randomly assigned to an OLM (10 mg/day) group or a control group. Hemodynamic states, oxidative stress, renal function and AGEs were measured after 8 weeks of OLM treatment. RESULTS: All the hemodynamic derangements associated with renal and cardiovascular dysfunctions were abrogated in CRF rats receiving OLM. Decreased cardiac output was normalized compared to control (p <0.05). Mean aortic pressure, total peripheral resistance and left ventricular weight/body weight ratio were reduced by 21.6% (p <0.05), 28.2% (p <0.05) and 27.2% ((p <0.05). OLM also showed beneficial effects on the oscillatory components of the ventricular after-load, including 39% reduction in aortic characteristic impedance (p < 0.05), 75.3% increase in aortic compliance (p <0.05) and 50.3% increase in wave transit time (p < 0.05). These results implied that OLM attenuated the increased systolic load of the left ventricle and prevented cardiac hypertrophy in CRF rats. Improved renal function was also reflected by increases in the clearances of BUN (28.7%) and serum creatinine (SCr, 38.8%). In addition to these functional improvements, OLM specifically reduced the levels of malondialdehyde (MDA) equivalents in aorta and serum by 14.3% and 25.1%, as well as the amount of AGEs in the aortic wall by 32% (p < 0.05) of CRF rats. CONCLUSION: OLM treatment could ameliorate arterial stiffness in CRF rats with concomitant inhibition of MDA and AGEs levels through the reduction of oxidative stress in aortic wall.

Detecting Volemic, Cardiac, and Autonomic Responses From Hypervolemia to Normovolemia via Non-Invasive ClearSight Hemodynamic Monitoring During Hemodialysis: An Observational Investigation.

Background: Unstable hemodynamics are not uncommon during hemodialysis (HD), which involves a rapid volume depletion, taking the patient from hypervolemia toward euvolemia. Since uremic patients commonly have cardiovascular comorbidities, hemodynamic changes during HD may reflect interactions among the volemic, cardiac, and autonomic responses to gradual volume depletion during ultrafiltration. Accurate identification of inappropriate responses helps with precisely managing intradialytic hypotension. Recently, the non-invasive ClearSight was reported to be able to detect causes of intraoperative hypotension. In this prospective observational study, we aimed to determine whether ClearSight could be used to detect patterns in stroke volemic, cardiac, and vasoreactive responses during HD. Methods: ClearSight was used to monitor chronic stable patients receiving maintenance HD. Data of mean arterial blood pressure (MAP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), and calculated systemic vascular resistance index (SVRI) were obtained and analyzed to examine patterns in volemic, cardiac, and vasoreactive changes from T0 (before HD) until T8 in 30-min intervals (total 4 h). Results: A total of 56 patients with a mean age of 60.5 years were recruited, of which 40 of them were men. The average ultrafiltration volume at T8 was 2.1 ± 0.8 L. The changes in MAP and HR from T0 to T8 were non-significant. SVI at T7 was significantly lower than that at T1, T2, and T3. CI at T4 to T8 was significantly lower than that at T0. SVRI was significantly higher at T3 to T8 than at T0. Pearson's correlation coefficients between SVI and CI and between SVRI and MAP were positive at all time points. The correlation coefficients between SVRI and SVI and between CI and SVRI were significant and negative for all time points. Conclusion: ClearSight was able to detect patterns in hypervolemia during HD and was well tolerated for 4 h. CI decreased significantly after T4, with slightly decreased SVI. Ultrafiltration volume was not correlated with changes in SVI or CI. The vascular tone increased significantly, and this counteracted the reduced cardiac output after T4. With simultaneous monitoring on SVI, CI, and SVRI during HD, therefore, hypotension could be detected and managed by reducing the filtration rate or administering inotrope or vasopressors. Trial Registration: clinicaltrials.gov, ID: NCT03901794.

Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial.

BACKGROUND: We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. METHODS: This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. RESULTS: A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). CONCLUSIONS: Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Associations of metabolic syndrome and its components with cardiovascular outcomes among non-diabetic patients undergoing maintenance peritoneal dialysis.

BACKGROUND: Metabolic syndrome (MS) is thought to be a risk marker for cardiovascular diseases in the general population and in patients with chronic kidney disease. This study investigated whether the presence of MS also modifies cardiovascular (CV) outcomes among non-diabetic patients undergoing long-term peritoneal dialysis (PD). METHODS: We enrolled 280 patients from a medical centre in North Taiwan who began PD between January 1999 and December 2005 and followed them until December 2009. MS was defined by the modified National Cholesterol Educational Programme (Adult Treatment Panel III) criteria. All parameters and biochemical data were collected by chart review. Patient outcomes (overall and CV death, fatal or non-fatal CV events) were recorded during the follow-up period. Survival was analysed by the Kaplan-Meier method, and the influence of MS and its components on outcomes were analysed by Cox regression models. RESULTS: The average follow-up period was 49.2 months. Non-diabetic patients with MS had worse outcomes than those without MS or at risk for MS, but better than their diabetic counterparts. By multivariate analysis, MS was independently associated with increased risk for CV death (hazard ratio, HR = 13.27) and fatal or non-fatal CV events (HR = 10.50). Among five MS components, hypertriglyceridaemia, low high-density lipoprotein levels and hyperglycaemia were significant risk factors for adverse CV outcomes. CONCLUSIONS: MS is a potent risk marker for adverse CV outcomes in non-diabetic patients on PD. Timely interventions targeting specific component of this syndrome may be required in this subset of patients.

Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients: a randomized, open-label, parallel-group study.

BACKGROUND AND OBJECTIVE: Hyperphosphataemia in end-stage renal disease (ESRD) is a major contributor to the development of cardiovascular disease. It has been proposed that the phosphate binder sevelamer has pleiotropic properties. The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles, uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia. METHODS: An 8-week, randomized, open-label, parallel-group study was conducted after a 2-week washout period. A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment; 26 patients were randomized to each of the sevelamer and calcium acetate groups. Reactive oxygen species (ROS) production, i.e. superoxide and hydrogen peroxide (H2O2)-related radicals, were detected by chemiluminescence measurement with lucigenin and luminol, respectively. RESULTS: There were no significant differences between treatment groups in changes in serum phosphorus (p=0.378) and adjusted serum calcium levels (p=0.980), but there were more hypercalcaemic events in the calcium acetate group (12.0% vs 3.7%) during treatment. Total serum cholesterol (p<0.001) and low-density lipoprotein (LDL) cholesterol (p<0.001) levels decreased significantly compared with baseline in the sevelamer group. The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment (correlation coefficient [r]=0.266 and 0.386, respectively). Serum uric acid decreased significantly in the sevelamer group (p=0.020), and this change was correlated with serum phosphorus changes (r=0.458). Decreases in plasma H2O2-related radicals, the major oxidative stressor in ROS (p<0.001), but not superoxide (p=0.593), were observed after sevelamer treatment. CONCLUSION: The improvements in multiple lipid surrogates, uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease.

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients.

Background: Galactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear. Methods: Ninety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients. Results: At baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression. Conclusions: Our results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.

Associations between urinary cysteine-rich protein 61 excretion and kidney function decline in outpatients with chronic kidney disease: a prospective cohort study in Taiwan.

OBJECTIVES: To examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline. DESIGN: An observational cohort study. SETTING: In the nephrology outpatient clinics of a tertiary hospital in Taiwan. PARTICIPANTS: We enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women. PRIMARY OUTCOME MEASURES: Urinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m2/year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables. RESULTS: The urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up. CONCLUSIONS: Elevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning.

Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats.

BACKGROUND: We compared the haemodynamic and metabolic effects of acetyl-L-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) in streptozotocin-induced diabetes in male Wistar rats. MATERIALS AND METHODS: Diabetes was induced by a single tail vein injection of 55mgkg(-1) streptozotocin. The diabetic animals daily treated with either acetyl-L-carnitine (150mgkg(-1) in drinking water) or oxfenicine (150mgkg(-1) by oral gavage) for 8weeks,were compared with the untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. RESULTS: Oxfenicine, but not acetyl-L-carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl-L-carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl-L-carnitine may attenuate the diabetes-induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls in diabetes. Acetyl-L-carnitine therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. CONCLUSION: Acetyl-L-carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived MDA/TBARS in the rats with insulin deficiency.

Life expectancy, expected years of life lost and survival of hemodialysis and peritoneal dialysis patients.

BACKGROUND: Expected years of life lost (EYLL) in dialysis patients are rarely discussed. This study compared life expectancy, EYLL and survival between hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Adults who underwent maintenance dialysis at National Taiwan University Hospital from 1995 to 2006 were followed up until December 2007. Kaplan-Meier analysis and a constant excess hazard model were used to estimate and project long-term survival. EYLL was calculated by subtracting the life expectancy of patients from that of age- and sex-matched referents. HD patients were then matched with PD patients on age, sex and diabetes mellitus (DM). Life expectancy, EYLL and survival between the 2 groups were compared. Mortality risks were determined by the Cox model. RESULTS: Before matching, the 305 HD patients were older than the 428 PD patients (62.4 ± 13.7 vs. 53.1 ± 16.7 years; p<0.0001). More HD patients had DM (HD vs. PD, 29.2% vs. 20.6%; p=0.0072). Life expectancy and EYLL of HD patients were 8.8 and 11.5 years, compared with those of PD patients (19.9 and 7.4 years). After matching, life expectancy (p=0.790) and EYLL (p=0.793) of both groups (236 patients each) were similar. Age (adjusted hazard ratio [AHR] = 1.07; 95% confidence interval [95% CI], 1.05-1.09) and DM (AHR=3.81; 95% CI, 2.28-6.36) were independent mortality predictors. For diabetic patients who underwent HD, a better survival rate was observed (AHR=0.24; 95% CI, 0.11-0.53). CONCLUSIONS: After matching, HD and PD patients had similar life expectancy and EYLL. Survival was better for diabetic patients if they received HD.

Benefits of sevelamer on markers of bone turnover in Taiwanese hemodialysis patients.

BACKGROUND/PURPOSE: Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. METHODS: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. RESULTS: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). CONCLUSION: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism.

Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis.

AIM: Patients with end-stage renal disease (ESRD) often start long-term haemodialysis (HD) thrice weekly, regardless of the level of residual renal function (RRF). In this study, we investigated whether ESRD patients having sufficient RRF can be maintained on twice-weekly HD, and how they fare compared to patients without RRF on thrice-weekly HD. METHODS: We analyzed 74 patients who had undergone long-term HD and maintained on the same dialysis frequency from February 1998 to July 2005, and followed until December 2005. We compared the clinical variables between twice-weekly and thrice-weekly HD patients and a second analysis testing the residual urine output as an independent predictor for twice-weekly HD. RESULTS: After a mean follow up of 18 months, twice-weekly HD patients (n = 23) had lower serum beta2-microglobulin than thrice-weekly HD patients (n = 51). Moreover, the twice-weekly group had a slower decline of RRF, as indicated by their higher urine output and creatinine clearance, fewer intradialytic hypotensive episodes, and required less frequent hospitalization. There was no difference between the two groups in cardiothoracic ratio or indices of nutrition and inflammation. Multivariable logistic regression identified age (odds ratio (OR), 1.866; 95% CI, 1.093-3.183), dry body mass index (OR, 0.790; 95% CI, 0.625-0.999), and urine output (OR, 1.093; 95% CI, 1.026-1.164) as predictors for maintaining twice-weekly HD. CONCLUSION: Our data suggest that when patients who have sufficient urine output are given twice-weekly HD, they maintain dialysis adequacy and exhibit better preservation of RRF than patients on thrice-weekly HD.

Seven-year follow-up of peritoneal dialysis patients in Taiwan.

BACKGROUND: There are no Taiwanese publications and only a few Asian publications on the long-term outcome of peritoneal dialysis (PD) patients. The aim of this study was to evaluate the outcome of PD patients in Taiwan during a 7-year follow-up period. PATIENTS AND METHODS: This study enrolled 67 patients (23 males, mean age 46.2 +/- 14.5 years) on maintenance PD. We administered the Short-Form questionnaire on 30 September 1998 and recorded major events and outcomes until 30 September 2005. We compared differences in initial parameters between groups categorized by PD patient survival and PD technique survival. Causes of mortality and transfer to hemodialysis were determined. PD patient and PD technique survival rates were measured and risk factors for patient mortality and PD technique failure were analyzed. RESULTS: Those in patient survival or PD technique survival groups had lower mean age (p < 0.001 and 0.018 respectively) and higher serum albumin level (p = 0.015 and 0.041 respectively) compared to those that died or failed PD. The 7-year patient survival rate was 77% and the PD technique survival rate was 58%. The independent predictors for PD technique failure included lower Mental Component Summary scores [hazard ratio (HR) = 0.85, p = 0.031] and diabetes mellitus (HR = 4.63, p < 0.001), whereas lower serum albumin level (HR = 0.22, p = 0.031), lower Physical Component Summary scores (HR = 0.67, p = 0.047), and presence of diabetes mellitus (HR = 5.123, p = 0.009) were the independent predictors for patient mortality. CONCLUSION: For our PD patients, both patient and technique survival rates are good. Better glycemic control, adequate nutrition, and enhancement of health-related quality of life are all of potential prognostic benefit.