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1.  Difference between CKD-EPI and MDRD equations in calculating glomerular filtration rate in patients with cirrhosis 
AIM: To evaluate the difference between the performance of the (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations in cirrhotic patients.
METHODS: From Jan 2004 to Oct 2008, 4127 cirrhotic patients were reviewed. Patients with incomplete data with respect to renal function were excluded; thus, a total of 3791 patients were included in the study. The glomerular filtration rate (GFR) was estimated by the 4-variable MDRD (MDRD-4), 6-variable MDRD (MDRD-6), and CKD-EPI equations.
RESULTS: When serum creatinine was 0.7-6.8 mg/dL and 0.6-5.3 mg/dL in men and women, respectively, a significantly lower GFR was estimated by the MDRD-6 than by the CKD-EPI. Similar GFRs were calculated by both equations when creatinine was > 6.9 mg/dL and > 5.4 mg/dL in men and women, respectively. In predicting in-hospital mortality, estimated GFR obtained by the MDRD-6 showed better accuracy [81.72%; 95% confidence interval (CI), 0.94-0.95] than that obtained by the MDRD-4 (80.22%; 95%CI, 0.96-0.97), CKD-EPI (79.93%; 95%CI, 0.96-0.96), and creatinine (77.50%; 95%CI, 2.27-2.63).
CONCLUSION: GFR calculated by the 6-variable MDRD equation may be closer to the true GFR than that calculated by the CKD-EPI equation.
PMCID: PMC3218145  PMID: 22110285
Chronic Kidney Disease Epidemiology Collaboration; Estimated glomerular filtration rate; Liver cirrhosis; Modification of Diet in Renal Disease; Renal function
2.  Is an estimated glomerular filtration rate better than creatinine to be incorporated into the end-stage liver disease score? 
World Journal of Hepatology  2012;4(11):291-298.
AIM: To incorporate estimated glomerular filtration rate (eGFR) into the model for end-stage liver disease (MELD) score to evaluate the predictive value.
METHODS: From January 2004 to October 2008, the records of 4127 admitted cirrhotic patients were reviewed. Patients who survived and were followed up as outpatients were defined as survivors and their most recent available laboratory data were collected. Patients whose records indicated death at any time during the hospital stay were defined as non-survivors (in-hospital mortality). Patients with incomplete data or with cirrhosis due to a congenital abnormality such as primary biliary cirrhosis were excluded; thus, a total of 3857 patients were enrolled in the present study. The eGFR, which was calculated by using either the modification of diet in renal disease (MDRD) equation or the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, was incorporated into the MELD score after adjustment with the original MELD equation by logistic regression analysis [bilirubin and international normalized ratio (INR) were set at 1.0 for values less than 1.0].
RESULTS: Patients defined as survivors were significantly younger, had a lower incidence of hepatoma, lower Child-Pugh and MELD scores, and better renal function. The underlying causes of cirrhosis were very different from those in Western countries. In Taiwan, most cirrhotic patients were associated with the hepatitis virus, especially hepatitis B. There were 16 parameters included in univariate logistic regression analysis to predict in-hospital mortality and those with significant predicting values were included in further multivariate analysis. Both 4-variable MDRD eGFR and 6-variable MDRD eGFR, rather than creatinine, were significant predictors of in-hospital mortality. Three new equations were constructed (MELD-MDRD-4, MELD-MDRD-6, MELD-CKD-EPI). As expected, original MELD score was a significant predictor of in-hospital mortality (odds ratio = 1.25, P < 0.001). MELD-MDRD-4 excluded serum creatinine, with the coefficients refit among the remaining 3 variables, i.e., total bilirubin, INR and 4-variable MDRD eGFR. This model represented an exacerbated outcome over MELD score, as suggested by a decrease in chi-square (2161.45 vs 2198.32) and an increase in -2 log (likelihood) (2810.77 vs 2773.90). MELD-MDRD-6 included 6-variable MDRD eGFR as one of the variables and showed an improvement over MELD score, as suggested by an increase in chi-square (2293.82 vs 2198.32) and a decrease in -2 log (likelihood) (2810.77 vs 2664.79). Finally, when serum creatinine was replaced by CKD-EPI eGFR, it showed a slight improvement compared to the original MELD score (chi-square: 2199.16, -2 log (likelihood): 2773.07). In the receiver-operating characteristic curve, the MELD-MDRD-6 score showed a marginal improvement in area under the curve (0.909 vs 0.902), sensitivity (0.854 vs 0.819) and specificity (0.818 vs 0.839) compared to the original MELD equation. In patients with a different eGFR, the MELD-MDRD-6 equation showed a better predictive value in patients with eGFR ≥ 90, 60-89, 30-59 and 15-29.
CONCLUSION: Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score.
PMCID: PMC3536835  PMID: 23293714
Liver cirrhosis; Estimated glomerular filtration rate; End-stage liver disease; Modification of diet in renal disease; Renal function
3.  P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients 
BioMed Research International  2014;2014:526932.
Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study. Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up. Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12, P = 0.01), cardiovascular disease history (HR: 6.28, P = 0.02), and PCS (HR: 1.12, P = 0.02) were independently associated with cardiovascular event; age (HR: 0.91, P < 0.01), serum albumin (HR: 0.03, P < 0.01), and PCS level (HR: 1.17, P < 0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rank P = 0.03, log rank P < 0.01, resp.). Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.
PMCID: PMC3925630  PMID: 24592393
4.  Serum p-cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients 
Previous studies have shown that serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were significantly related to clinical outcomes in patients on hemodialysis (HD). However, evidence for the relationship in elderly HD patients remains scarce. We explore whether the two toxins can predict clinical outcomes in elderly HD patients.
Material and methods
Fifty stable HD patients more than 65 years old were enrolled from a single medical center. Serum total and free PCS, IS levels and biochemistry were measured concurrently. The clinical outcomes including cardiovascular events and all-cause mortality were analyzed after 38-month follow-up.
Univariate Cox proportional hazard ratio analysis revealed that cardiovascular events were associated with gender (p = 0.02), diabetes (p < 0.01), calcium (p = 0.01), total PCS (p < 0.01), free PCS (p < 0.01) and total IS (p = 0.05). Multivariate analysis showed that diabetes (p = 0.01), total PCS (p = 0.01) and free PCS (p = 0.04) were related to cardiovascular events. For all-cause mortality, only total PCS (p = 0.01) reached significance after adjusting other confounding factors. However, Kaplan-Meier analysis indicated that free PCS (p = 0.02) and total PCS (p < 0.01) were significantly associated with cardiovascular events and total PCS (p = 0.048) was related to all-cause mortality during 38-month follow-up.
Our results indicate that total PCS is a valuable marker in predicting cardiovascular event and all-cause mortality in elderly HD patients.
PMCID: PMC3776179  PMID: 24049526
hemodialysis; p-cresyl sulfate; indoxyl sulfate; cardiovascular disease; mortality
5.  Neuroprotection by the Traditional Chinese Medicine, Tao-Hong-Si-Wu-Tang, against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia in Rats 
Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese medicine (TMC). In the present study, oral administration of THSWT (0.7 and 1.4 g kg−1day−1) for 14 days before MCAO dose-dependently attenuated focal cerebral ischemia in rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and active caspase-3 expressions in ischemic regions. These expressions were obviously inhibited by 0.7 g kg−1day−1 THSWT treatment. In addition, THSWT inhibited platelet aggregation stimulated by collagen in washed platelets. In an in vivo study, THSWT (16 g kg−1) significantly prolonged platelet plug formation in mice. However, THSWT (20 and 40 μg mL−1) did not significantly reduce the electron spin resonance (ESR) signal intensity of hydroxyl radical (OH•) formation. In conclusion, the most important findings of this study demonstrate for the first time that THSWT possesses potent neuroprotective activity against MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and platelet activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
PMCID: PMC2975073  PMID: 21076527
6.  Peripheral artery disease in peritoneal dialysis and hemodialysis patients: single-center retrospective study in Taiwan 
BMC Nephrology  2012;13:100.
Peripheral artery disease (PAD) is a condition characterized by restricted blood flow to the extremities, and is especially common in the elderly. PAD increases the risk for mortality and morbidity in patients with end-stage renal disease (ESRD), especially those on hemodialysis (HD).
The records of 484 patients with end-stage renal disease who were on HD or peritoneal dialysis (PD) were reviewed. PAD was diagnosed based on the ankle-brachial pressure index (ABI). Demographic and clinical characteristics were analyzed.
PAD had an overall prevalence of 18.2% and was significantly more common in HD patients (21.8%) than in PD patients (4.8%). Advanced age, diabetes mellitus, smoking, low parathyroid hormone level, elevated serum ferritin, elevated serum glucose, and low serum creatinine levels increased the risk for PAD. PAD was independently associated with advanced age, diabetes mellitus, duration of dialysis, low serum creatinine, and hyperlipidemia. PD patients had a significantly lower prevalence of PAD than HD patients, maybe due to their younger age and lower prevalence of diabetes mellitus in this present study.
The prevalence of PAD was greater in the HD group than the PD group. Most of the risk factors for PAD were specific to HD, and no analyzed factor was significantly associated with PAD in PD patients.
PMCID: PMC3447712  PMID: 22943313
Ankle-brachial pressure index (ABI); Cardiovascular disease; End-stage renal disease; Hemodialysis; Peritoneal dialysis; Peripheral artery disease
7.  Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase 
The Scientific World Journal  2012;2012:503945.
Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n = 23) or who did not develop refractory SHPT (control subjects; n = 25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.
PMCID: PMC3417170  PMID: 22919331

Results 1-7 (7)