Randomized Study of Darbepoetin Alfa and Recombinant Human Erythropoietin for Treatment of Renal Anemia in Chronic Renal Failure Patients Receiving Peritoneal Dialysis

Background/PurposeDarbepoetin alfa can be administered less frequently than recombinant human erythropoietin (r-HuEPO) for the treatment of anemia in chronic renal failure (CRF) patients. We aimed to confirm that darbepoetin alfa at a reduced dosing schedule can safely maintain a target hemoglobin level in CRF patients undergoing peritoneal dialysis.MethodsForty-five PD patients receiving r-HuEPO were randomized in a 1:1 ratio to continue r-HuEPO or to change to darbepoetin alfa (open-label). Patients were maintained within a target range of hemoglobin for 5.5 months by adjusting the dose and then the frequency of darbepoetin alfa and r-HuEPO over the initial 4 months. The evaluation period was the final 1.5 months. A total of 37 patients completed the study.ResultsDuring the evaluation period, the hemoglobin of the darbepoetin alfa group was higher than that in the baseline period (10.46 ± 0.22 g/dL vs. 9.98 ± 0.18 g/dL, p < 0.05). Hemoglobin remained similar in the r-HuEPO group. The average dose in the darbepoetin alfa group was 93.0 μg/month, while the average dose in the r-HuEPO group was 18,339.9 units/month. The dosing frequency was less in the darbepoetin alfa group (3.9 times/month vs. 9.2 times/month). We divided the darbepoetin alfa group into low-dose (< 70 μg/month) and high-dose (≥ 70 μg/month) subgroups. The body weight in the high-dose group was higher than that in the low-dose group (66 ± 11 kg vs. 52 ± 4.4 kg, p < 0.01).ConclusionBoth darbepoetin alfa and r-HuEPO safely maintain hemoglobin levels within the target range in peritoneal dialysis patients

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45ml/min per 1.73m2. AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 3.3) than patients with AKI but without CKD. The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge

Safety Issues of Long-Term Glucose Load in Patients on Peritoneal Dialysis—A 7-Year Cohort Study

BACKGROUND: Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. METHODS: We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates. RESULTS: We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. CONCLUSIONS: Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients

Factors associated with low bone mass in the hemodialysis patients – a cross-sectional correlation study

<p>Abstract</p> <p>Background</p> <p>Low bone mass is common in end-stage renal disease patients, especially those undergoing hemodialysis. It can lead to serious bone health problems such as fragility fractures. The purpose of this study is to investigate the risk factors of low bone mass in the hemodialysis patients.</p> <p>Methods</p> <p>Sixty-three subjects on hemodialysis for at least 6 months were recruited from a single center for this cross-sectional study. We collected data by questionnaire survey and medical records review. All subjects underwent a bone mineral density (BMD) assay with dual-energy x-ray absorptiometry at the lumbar spine and right hip. Data were statistically analyzed by means of descriptive analysis, independent t test and one way analysis of variance for continuous variables, Pearson product-moment correlation to explore the correlated factors of BMD, and stepwise multiple linear regression to identify the predictors of low bone mass.</p> <p>Results</p> <p>Using WHO criteria as a cutoff point, fifty-one subjects (81%) had a T-score lower than -1, of them 8 subjects (13%) had osteoporosis with the femoral neck most commonly affected. Regarding risk factors, age, serum alkaline phosphatase (ALP) level, and intact parathyroid hormone (iPTH) level had significant negative correlations with the femoral neck and lumbar spine BMD. On the other hand, serum albumin level, effective exercise time, and body weight (BW) had significant positive correlations with the femoral neck and lumbar spine BMD. Age, effective exercise time, and serum albumin level significantly predicted the femoral neck BMD (R²× 0.25), whereas BW and the ALP level significantly predicted the lumbar spine BMD (R²× 0.20).</p> <p>Conclusion</p> <p>This study showed that advanced age, low BW, low serum albumin level, and high ALP and iPTH levels were associated with a low bone mass in the hemodialysis patients. We suggest that regular monitoring of the femoral neck BMD, maintaining an adequate serum albumin level and BW, and undertaking an exercise program are important to improve bone health in the patients undergoing hemodialysis.</p

血管舒張劑抑負鼠近端賢小管細胞增生

Renal tubule cell hyperplasia and hypertrophy have been regarded as antecedents of tubulointerstitial fibrosis. Dipyridamole and pentoxifylline inhibit rat glomerular mesangial cell growth. The purpose of this study was to examine the effects of pentoxifylline and other vasodilators on opossum kidney proximal tubular (OKP) cell growth. A modified 3-(4, 5-dimethylthiazil-2-yl)-2, 5- diphenyltetrazolium bromide assay was used to evaluate cell proliferation in OKP cells. Pentoxifylline caused a dose- dependent inhibition of serum-stimulated proliferation of OKP cells: inhibition was 17%, 25%, and 37% at 0.03 mg/mL, 0 .1 mg/mL, and 0.3 mg/mL, respectively. Dipyridamole 1.7 mg/L and 6 mg/L resulted in 34% and 46% inhibition, respectively . Verapamil 10^(-6) M, 10^(-5) M, and 10 ^(-4) M resulted in 34%, 46%, and 67% inhibitory, respectively. These inhibitory effects may contribute to renal protection or retardation of renal disease progression

內皮素在腎小管細胞活化mapk及調節細胞周期蛋白

Background/Purpose: The signaling mechanisms through which endothelin (ET )-1 induces hyperplasia of the renal tubular epithelium are largely unknown. Methods: These mechanisms were explored using ETB-overexpressing opossum kidney (OKP) cells as a model system. Results: ET-1 (10 nM) induced a 10- fold increase in c jun mRNA abundance within 30 minutes and an 8-fold increase in extracellular signal-regulated kinase (ERK) 1/2 activity within 5-10 minutes in these cells. ERK1/ 2 phosphorylation in response to ET-1 was suppressed by ETB - receptor blockade or by treatment with an MAPK kinase (MEK ) inhibitor. MEK1/2 activity increased 8-fold within 5 minutes of ET-1 treatment. Additionally 2-fold increases in cyclin D1 expression and retinoblastoma (RB) gene product phosphorylation were observed within 4 hours of treatment. Conclusion: Binding of ET-1 to the ET receptor of ETB- overexpressing OKP cells is proposed to signal proliferation of these cells through rapid activation of mitogen- activated protein kinases, increased c jun expression, modulation of cyclin D1 activity, and increased RB phosphorylation