Ping-Fang Chiu

Warfarin slows deterioration of renal function in elderly patients with chronic kidney disease and atrial fibrillation

Background The purpose of this study was to examine whether long-term use of anticoagulants in elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) influences renal function. Methods In this retrospective observational study, we reviewed the records of 2023 patients who attended our institution for treatment of CKD between January 2001 and September 2012. Inclusion criteria were having been under review for three months or more, age older than 60 years, permanent AF, a CHADS2 score > 2, and National Kidney Foundation Kidney Disease Outcomes Quality Initiative CKD stage 3–5. Sixty-one patients fulfilled these criteria, and were divided into those receiving antiplatelet anticoagulation (group A) and those receiving warfarin (group B). The results of laboratory investigations and estimated glomerular filtration rate (GFR) were recorded at months 3, 6, 12, and 18 from treatment initiation. We also recorded the occurrence of serious cardiovascular and neurological events, significant bleeding, and survival beyond 12 years. Results Of the 61 patients enrolled, 35 were in group A and 26 were in group B. The mean international normalized ratio (INR) was 1.95 ± 1.01 (goal < 3.0). After adjustment for potential confounding variables, we found that patients in group B had a higher estimated GFR (6.06 ± 2.36 mL per minute, P = 0.01). Over a 12-year observation period, group B patients had significantly (P = 0.013) better survival than group A, with an adjusted hazard ratio for mortality of 0.318 (P = 0.022). Conclusion Warfarin therapy may delay deterioration in renal function and improve survival of elderly patients with CKD and AF.

Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study.

Background There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes. Methods In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson’s comorbidity index score-matched controls. Results The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36–1.50, P<0.001). Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001) and those with concomitant diabetes mellitus (aHR 2.12, P<0.001), hyperlipidemia (aHR 1.53, P<0.001) or gout (aHR 1.84, P<0.001) were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD) were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively), independent of age, sex, comorbidities and long-term medications. Conclusions Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases.

Sustained Low-Efficiency Daily Diafiltration with Hemoperfusion as a Therapy for Severe Star Fruit Intoxication: A Report of Two Cases

Abstract Over the past decade, star fruit (Averrhoa carambola) intoxication decreased in the Taiwanese society due to improved public education on chronic kidney disease (CKD). Various complications including hiccups, altered levels of consciousness, coma, and seizures have been reported in individuals with renal failure who ingested fresh star fruit or star fruit juice. A high mortality rate (from 33 to 80%) was observed in patients with altered levels of consciousness, despite prompt dialysis and supportive care. According to previous case reports, the proposed treatment of choice for severe star fruit intoxication may be continuous renal replacement therapy with or without hemoperfusion. We report two cases of star fruit intoxication with stage V CKD (one case is predialysis) presenting with coma and generalized tonic-clonic seizures. The two patients were treated with sustained low-efficiency daily diafiltration (SLEDD-f) and charcoal hemoperfusion. Status epilepticus was controlled fairly quickly after treatment with SLEDD-f and hemoperfusion. However, the outcomes in this report are still poor (both remained comatose; one of two patients died). Currently, there are no data for the use of SLEDD-f with hemoperfusion for severe star fruit intoxication. SLEDD-f with charcoal hemoperfusion may play a role in managing refractory status epilepticus in patients with severe star fruit poisoning.

The Predictive Role of Red Cell Distribution Width in Mortality among Chronic Kidney Disease Patients

Background Recently, accumulating evidence has demonstrated that RDW independently predicts clinically important outcomes in many populations. However, the role of RDW has not been elucidated in chronic kidney disease (CKD) patients. We conducted the present study with the aim to evaluate the predictive value of RDW in CKD patients. Methods A retrospective observational cohort study of 1075 stage 3–5 CKD patients was conducted in a medical center. The patients’ baseline information included demographic data, laboratory values, medications, and comorbid conditions. The upper limit of normal RDW value (14.9%) was used to divide the whole population. Multivariate Cox regression analysis was used to determine the independent predictors of mortality. Results Of the 1075 participants, 158 patients (14.7%) died over a mean follow-up of approximately 2.35 years. The crude mortality rate was significantly higher in the high RDW group (high RDW group, 22.4%; low RDW group 11%, p <0.001). From the adjusted model, the high RDW group was correlated with a hazard ratio of 2.19 for overall mortality as compared with the low RDW group (95% CI = 1.53–3.09, p<0.001). In addition, the high RDW group was also associated with an increased risk for cardiovascular disease (HR = 2.28, 95% CI = 1.14–4.25, p = 0.019) and infection (HR = 1.9, 95% CI = 1.15–3.14, p = 0.012)) related mortality in comparison with the low RDW group. Conclusions In stage 3–5 CKD patients, RDW was associated with patient mortality of all-cause, cardiovascular disease and infection. RDW should be considered as a clinical predictor for mortality when providing healthcare to CKD patients.

Long-term renal outcomes of episodic urinary tract infection in diabetic patients

OBJECTIVE Urinary tract infection (UTI) exists in 9%-20% of female and 3%-11% of male patients with diabetes. Diabetic patients experience increased risk of bacteremia, hospitalization, and mortality; however, few studies report long-term renal outcomes of episodic UTI in diabetic patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS We investigated 225 diabetic patients admitted with UTI from 2001 to 2011. Based on the glomerular filtration rate (GFR) on admission, we divided the patients into early- (GFR ≥30 ml/min; n=131) and late-stage (stages 4 and 5, GFR <30 ml/min; n=94) CKD groups. We compared admission risk factors, post-UTI GFR decline and its long term trend between these groups. RESULTS Poor glycemic control contributed to admission with UTI in the early- and late-stage CKD patients (glycosylated hemoglobin: (9.7±2.8% versus 8.6±2.6%). Early-stage CKD patients exhibited higher urinary glucose. Besides, acute kidney injury (AKI) occurred on admission in late-stage CKD patients (mean eGFR 14.2 ml/min). However, if the infection was cured, almost all diabetic patients reverted to their GFR trends 6 months later. CONCLUSIONS Late-stage CKD diabetic patients with UTI are at increased risk of superimposed AKI. Almost all patients gradually reverted to their GFR trend later after infection was cured. Early recognition of complicating AKI factors and aggressive treatment of symptomatic UTI instead of antibiotic prophylaxis for asymptomatic bacteriuria are suggested.

Simvastatin downregulates the expression of hepcidin and erythropoietin in HepG2 cells.

Statin therapy may improve responsiveness to erythropoietin‐stimulating agents in patients with end‐stage renal disease. Although statins increase hepatic iron uptake and storage capacity in cholestatic rats, the underlying mechanisms are unclear. Therefore, we examined the effects of a statin (simvastatin) on the expression of hepcidin, erythropoietin receptor (EPOR) and erythropoietin (EPO) in cultured HepG2 cells. HepG2 cells (6–6.5 × 105 cells) were seeded in 6‐cm dishes and incubated overnight. The cells were then treated with 0, 0.5, 1, 3, 5, or 10 μM simvastatin, and the mRNA expression of hepcidin, EPOR, and EPO was determined. Data were collected from three independent experiments. The cDNA extracted from the cells was used as a template for real‐time polymerase chain reaction, and each sample was tested in duplicate. Significant differences (P < 0.05) among groups were determined using one‐way analysis of variance with Fishers least significant difference post hoc test. Data were adjusted using Bonferronis method. The relative mRNA expression of hepcidin in HepG2 cells treated with 0.5, 1, 3, 5, and 10 μM simvastatin, relative to the control group, was 0.7273, 0.3303, 0.2418, 0.4131, and 0.4064, respectively. The relative mRNA expression of EPOR was 0.5196, 0.2319, 0.2398, 0.4253, and 0.1245, respectively, while that of EPO was 0.9751, 0.4712, 0.4613, 0.4875, and 0.1654. There was a reverse dose‐dependent effect of simvastatin. These results suggest that statins increase erythropoiesis by targeting hepcidin and iron regulatory pathways, independent of erythropoietin.

Trajectories of Serum Albumin Predict Survival of Peritoneal Dialysis Patients: A 15-year Follow-Up Study

AbstractAlthough initial serum albumin level is highly associated with overall and cardiovascular mortality in peritoneal dialysis (PD) patients, we consider that the dynamic change and trend of albumin after initiation of PD are also essential.We enrolled patients who received PD for more than 3 months from January 1999 to March 2014. We categorized these patients into 2 groups by the difference in serum albumin level (&Dgr;albumin = difference between peak with initial albumin level = peak albumin level − initial albumin level) after PD. The patients with &Dgr;albumin < 0.2 g/dL (median level) were considered as group A (n, number = 238) and those with &Dgr;albumin ≥ 0.2 g/dL were considered as group B (n = 278). Further, we stratified these patients into quartiles: Q1 &Dgr;albumin < −0.2 g/dL; Q2, −0.2 ≦∼ <0.2 g/dL; Q3, 0.2 ≦∼ <0.6 g/dL; and Q4, ≥0.6 g/dL. Regression analysis was performed to determine the correlation of initial albumin and &Dgr;albumin.Group A patients presented with higher levels of serum albumin (3.71 ± 0.54 vs 3.04 ± 0.55 g/dL; P < 0.001) and hematocrit as well as better initial residual renal function. However, those in group A had lower serum albumin increment and downward-sloped trends after dialysis. In contrast, the albumin trend was upward sloped and the increment of albumin was remarkable in group B, despite the high prevalence of cardiovascular diseases and diabetes. Overtime, group A patients had poorer survival and experienced more frequent and longer hospitalizations. Group Q1 patients with least albumin increment had worst survival. Group Q4 patients with lowest initial albumin also had poor survival. Age, diabetes, cardiovascular diseases, BMI, initial albumin, and &Dgr;albumin could affect patient outcomes independently. Regression analysis showed a better outcome can be obtained if the initial albumin level is at least above 3.15 g/dL. (Initial albumin level = −0.61 × &Dgr;albumin + 3.50.)The increment and trend of albumin especially during early period of PD may be a more crucial determinant for survival.

Lower-dose warfarin delays renal progression and prolongs patient survival in patients with stage 3 - 5 chronic kidney disease and nonvalvular atrial fibrillation: a 12-year follow-up study.

BACKGROUND Anticoagulants are used to reduce the risk of stroke in patients with atrial fibrillation (Af) and chronic kidney disease (CKD). Warfarin is one of the commonly used anticoagulants; however, its effect on renal function remains unclear. METHODS In a retrospective cohort study (January 2001 - July 2013), we surveyed data charts from 2,450 patients with stage 3 - 5 CKD, and enrolled 159 patients with Af. In total, 104 patients had a CHADS2 score of >= 2 (congestive heart failure, hypertension, >= 75 years old, diabetes, 1 point; prior stroke or transient ischemic attack or thromboembolism, 2 points). These patients were categorized into groups A and B based on warfarin treatment. Group A included 73 patients and was not undergoing warfarin treatment and group B included 31 patients undergoing warfarin treatment. The baseline demographic and biochemical data as well as changes in estimated glomerular filtration rate (eGFR) after 6, 12, and 18 months of warfarin treatment were analyzed. We also studied censored patient survival over 12 years using Kaplan-Meier model. RESULTS The mean international normalization ratio (INR) of warfarin treatment in group B was 1.92 ± 1.04. Moreover, group B showed a significant increase in eGFR. The maximum improvement was at 6 months (mean eGFR increased from 25.97 to 31.12 mL/min; p = 0.01) and lasted for up to 18 months (eGFR 28.65 mL/min). Despite higher initial CHADS2 scores, group B showed a superior survival rate compared with group A (p = 0.02). CONCLUSION Lower doses of warfarin may protect against renal dysfunction and could be beneficial for treatment of stage 3 - 5 CKD with Af.

Long-term renal outcomes in patients with traumatic brain injury: A nationwide population-based cohort study.

Background Traumatic brain injury (TBI) is an important cause of death and disability worldwide. The relationship between TBI and kidney diseases is largely unknown. Methods We aimed to determine whether TBI is associated with long-term adverse renal outcomes. We performed a nationwide, population-based, propensity score-matched cohort study of 32,152 TBI patients and 128,608 propensity score-matched controls. Data were collected by the National Health Insurance Research Database of Taiwan from 2000 to 2012. Our clinical outcomes were chronic kidney disease (CKD), end-stage renal disease (ESRD) and the composite endpoint of ESRD or all-cause mortality. Results The incidence rate of CKD was higher in the TBI than in the control cohort (8.99 vs. 7.4 per 1000 person-years). The TBI patients also showed higher risks of CKD (adjusted hazard ratio [aHR] 1.14, 95% confidence interval [CI] 1.08–1.20; P < 0.001) and composite endpoints (aHR 1.08, 95% CI 1.01–1.15; P = 0.022) than the control groups, but the ESRD was not significantly different between the groups. In subgroup analyses, the risks of incident CKD and composite endpoints were significantly raised in TBI patients aged < 65 years and/or without comorbidities. However, the risks of both CKD and composite outcome were little affected by the severity of TBI. Conclusions TBI has a modest but significant effect on incident CKD and composite endpoint, but not on ESRD alone. TBI patients under 65 are at greater risk of CKD and composite outcome than their older counterparts.

Lower blood glucose and variability are associated with earlier recovery from renal injury caused by episodic urinary tract infection in advanced type 2 diabetic chronic kidney disease.

Purpose In our previous study, type 2 diabetic chronic kidney disease (CKD) patients with glomerular filtration rates of <30 mL/min upon hospitalization for urinary tract infection (UTI) were at a risk for acute kidney injury. This study aimed to clarify the effect of glucose and its variability on renal outcomes during admission for the treatment of UTI. Materials and Methods Based on the date of renal recovery (RIFLE criteria: acute kidney injury occurred within 1–7 days and was sustained over 1 day), we divided these patients into early- (≤9 days, Group A) and late-recovery (>9 days, Group B) groups. The differences in the continuous and categorical variables of the two groups were assessed separately. The mean glucose levels and their variability (using the standard deviation and the coefficient of standard deviation) were compared at the fasting, midday pre-meal, evening pre-meal, and evening post-meal time points during hospitalization. We have organized the manuscript in a manner compliant with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. Results Acute kidney injury occurred within the two groups (p = 0.007 and p = 0.001, respectively). The early-morning blood glucose levels (149.7±44.0 mg/dL) and average blood glucose levels (185.6±52.0 mg/dL) were better in Group A (p = 0.01, p = 0.02). Group A patients also had lower glucose variability than Group B at the different time points (p<0.05). Group A also had earlier renal recovery. More relevant pathogens were identified from blood in Group B (p = 0.038). Conclusions Early-morning fasting and mean blood glucose levels and their variability can be good indicators of severe infection and predictors of renal outcome in type 2 diabetic patients with CKD and UTI.