Yi-Chun Tsai

Brachial-Ankle Pulse Wave Velocity and Rate of Renal Function Decline and Mortality in Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Increased arterial stiffness was reported to be associated with decreased estimated GFR (eGFR). Previous studies suggested that arterial stiffness might play a role in renal function progression in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether there was an independent association between brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, and renal function progression in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal study enrolled 145 patients with CKD stages 3 to 5. The baPWV was measured by using an ABI-form device. The change in renal function was estimated by eGFR slope. The study endpoints were defined as commencement of dialysis or death. RESULTS After a stepwise multivariate analysis, the eGFR slope was positively associated with baseline eGFR and negatively associated with hypertension and baPWV (β=-0.165, P=0.033). Seventeen patients entering dialysis, and eight deaths were recorded. Multivariate forward Cox regression analysis identified that higher baPWV (hazard ratio, 1.001; P=0.001), lower baseline eGFR, and higher serum phosphate level were independently associated with progression to commencement of dialysis or death. CONCLUSIONS Our results show an independent association between baPWV and renal function decline and progression to commencement of dialysis or death in patients with CKD. Screening CKD patients by means of baPWV may help identify a high-risk group of rapid renal function decline and progression to commencing dialysis or death.

Association of Symptoms of Depression With Progression of CKD

BACKGROUND Depression is related to morbidity and mortality in patients with kidney failure treated by dialysis, but its influence on patients with earlier stages of chronic kidney disease (CKD) is uncertain. This study investigates the association of depressive symptoms with clinical outcomes in patients with CKD not requiring dialysis. STUDY DESIGN Prospective observational cohort study. SETTING & PARTICIPANTS 568 participants with CKD not requiring maintenance dialysis were recruited consecutively at a tertiary hospital in Southern Taiwan and followed up for 4 years. PREDICTORS Baseline status of depressive symptoms. OUTCOMES The primary outcome is a composite of progression to end-stage renal disease (ESRD), defined as requiring maintenance dialysis treatment, or all-cause mortality; and secondary outcome was first hospitalization. MEASUREMENTS Depressive symptoms were assessed by Beck Depression Inventory. Estimated glomerular filtration rate (eGFR) was computed using the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. RESULTS 428 participants completed the questionnaires and 160 (37%) had depressive symptoms. During a mean follow-up of 25.2 ± 11.9 months, 136 participants (32%) reached the primary outcome (119 reached ESRD and 17 died) and 110 participants (26%) were hospitalized. High depressive symptoms increased the risk of progression to ESRD or death (HR, 1.66; 95% CI, 1.14-2.44) and first hospitalization (HR, 1.59; 95% CI, 1.03-2.47). Participants with high depressive symptoms had more rapid GFR decrease (eGFR slopes of -2.3 [25th-75th percentile, -5.3 to -0.4] vs -1.2 [25th-75th percentile, -3.5 to 0.3] mL/min/1.73 m(2) per year; P = 0.001) and initial dialysis treatment at a higher eGFR (OR for initiation of dialysis at eGFR >5 mL/min/1.73 m(2), 4.45; 95% CI, 1.44-13.78). LIMITATIONS A single-center study of Taiwanese, Beck Depression Inventory evaluates only depressive symptom burden. CONCLUSIONS Depressive symptoms in CKD are independent predictors of adverse clinical outcomes, including faster eGFR decrease, dialysis therapy initiation, death, or hospitalization. Depression should be evaluated early and treated in patients with CKD.

Association of Fluid Overload with Cardiovascular Morbidity and All-Cause Mortality in Stages 4 and 5 CKD

BACKGROUND AND OBJECTIVES Fluid overload is a common characteristic associated with renal progression in CKD. Additionally, fluid overload is an independent predictor of all-cause or cardiovascular mortality in patients on dialysis, but its influence on patients not on dialysis is uncertain. The aim of the study was to assess the relationship between the severity of fluid status and clinical outcomes in an advanced CKD cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In total, 478 predialysis patients with stages 4 and 5 CKD in the integrated CKD care program were enrolled from January of 2011 to December of 2011 and followed-up until August of 2013. The clinical outcomes included cardiovascular morbidity and all-cause mortality. The relative hydration status (overhydration/extracellular water) was used as the presentation of the severity of fluid status and measured using a body composition monitor. Overhydration/extracellular water >7% was defined as fluid overload. RESULTS Over a median follow-up period of 23.2 (12.6-26.4) months, 66 (13.8%) patients reached all-cause mortality or cardiovascular morbidity. The adjusted hazard ratio of the combined outcome of all-cause mortality or cardiovascular morbidity for every 1% higher overhydration/extracellular water was 1.08 (95% confidence interval, 1.04 to 1.12; P<0.001). The adjusted overhydration/extracellular water for the combined outcome of all-cause mortality or cardiovascular morbidity in participants with overhydration/extracellular water ≥7% compared with those with overhydration/extracellular water <7% was 1.93 (95% confidence interval, 1.01 to 3.69; P=0.04). In subgroup analysis, higher overhydration/extracellular water was consistently associated with increased risk for the combined outcome independent of diabetes, cardiovascular disease, and serum albumin. There was no significant interaction between all subgroups. CONCLUSIONS These findings suggest that fluid overload is an independent risk factor of the combined outcome of all-cause mortality or cardiovascular morbidity in patients with advanced CKD.

Association of fluid overload with kidney disease progression in advanced CKD: a prospective cohort study.

BACKGROUND Fluid overload is a common phenomenon in patients in a late stage of chronic kidney disease (CKD). However, little is known about whether fluid overload is related to kidney disease progression in patients with CKD. Accordingly, the aim of the study was to assess the association of the severity of fluid status and kidney disease progression in an advanced CKD cohort. STUDY DESIGN Prospective observational cohort study. SETTING & PARTICIPANTS This cohort study enrolled 472 non-dialysis-dependent patients with CKD stages 4-5 who were in an integrated CKD care program from January 2011 to December 2011 and followed up until December 2012 or initiation of renal replacement therapy (RRT). PREDICTORS Tertile of fluid overload, with cutoff values at 0.6 and 1.6 L. OUTCOMES RRT, rapid estimated glomerular filtration rate (eGFR) decline (faster than 3 mL/min/1.73 m(2) per year), and change in eGFR. MEASUREMENTS The severity of fluid overload was measured by a bioimpedance spectroscopy method. eGFR was computed using the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. RESULTS During a median 17.3-month follow-up, 71 (15.0%) patients initiated RRT and 187 (39.6%) experienced rapid eGFR decline. The severity of fluid overload was associated with increased risk of RRT (tertile 3 vs tertile 1: adjusted HR, 3.16 [95% CI, 1.33-7.50]). Fluid overload value was associated with increased risk of rapid eGFR decline (tertile 3 vs tertile 1: adjusted OR, 4.68 [95% CI, 2.30-9.52]). Furthermore, the linear mixed-effects model showed that the reduction in eGFR over time was faster in tertile 3 than in tertile 1 (P=0.02). LIMITATIONS The effect of fluid volume variation over time must be considered. CONCLUSIONS Fluid overload is an independent risk factor associated with initiation of RRT and rapid eGFR decline in patients with advanced CKD.

Quality of life predicts risks of end-stage renal disease and mortality in patients with chronic kidney disease

BACKGROUND Quality of life (QOL) may be associated with morbidity and survival in end-stage renal disease (ESRD), and is considered to be an important outcome measure for patients with chronic kidney disease (CKD). However, the prognostic role of QOL for survival in CKD remains unclear. We studied the relationship between QOL and risks of ESRD and mortality in CKD patients. METHODS From 1 January 2007 to 31 December 2007, we prospectively used the Taiwan version of World Health Organization Quality-of-Life Questionnaire (Taiwan version) (WHOQOL-BREF(TW)) with 568 CKD patients at a medical centre in southern Taiwan, and patients were followed up for 1-2 years after enrollment. The primary outcome was the time to dialysis or death. We used Kaplan-Meier curve and Cox proportional hazard model for survival analyses. RESULTS Of the 568 patients enrolled, 423 were able to complete the questionnaires, and their data were analysed. The median follow-up time was 410 days. Progressive decreases in scores of QOL in all domains were noted with decrease in eGFR. In unadjusted analysis, dialysis and death were associated with lower scores of total and all four domains of WHOQOL-BREF(TW). In adjusted analysis, the total scores and scores of both physical and psychological domains predicted dialysis and mortality (every 1-point decrease hazard ratio (HR): 1.050, 95% CI: 1.008-1.095, P = 0.020; HR: 1.179, CI: 1.033-1.346, P = 0.014; HR: 1.167, CI: 1.016-1.339, P = 0.028, respectively). The adjusted risks of ESRD and mortality also increased in patients in the lowest tertile of psychological domain (P < 0.01), and physical domain and total scores (P < 0.05). CONCLUSIONS Physical, psychological and total scores of QOL are significantly correlated with increased risks of ESRD and death in CKD patients. QOL should be considered as an independent predictor of risks of ESRD and mortality.

Framingham Risk Score with Cardiovascular Events in Chronic Kidney Disease

The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as “low” (<10% of 10-year risk), “intermediate” (10–20% risk) or “high” risk (≧ 20% risk). A significant improvement in model prediction was based on the −2 log likelihood ratio statistic and c-statistic. “High” risk (v.s. “low” risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, “high” risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.

Association of Interleg BP Difference with Overall and Cardiovascular Mortality in Hemodialysis

BACKGROUND AND OBJECTIVES An interarm BP difference has been associated with atherosclerosis and adverse cardiovascular outcomes. This study investigated whether an interleg BP difference was associated with peripheral vascular disease and overall and cardiovascular mortality in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study enrolled 210 hemodialysis patients from December 2006 to January 2007. Bilateral leg BPs were measured simultaneously by an ankle-brachial index (ABI)-form device before hemodialysis. RESULTS The mean follow-up period was 4.4±1.5 years. ABI <0.9 and high brachial-ankle pulse wave velocity were independently associated with an interleg difference in systolic BP of ≥15 mmHg or diastolic BP of ≥10 mmHg. Furthermore, this difference was an independent predictor for overall mortality (hazard ratio [HR], 3.36; 95% confidence interval [CI], 1.68-6.72; P<0.01) and cardiovascular mortality (HR, 4.84; 95% CI, 1.84-12.71; P<0.01) after adjustment for demographic, clinical, and biochemical parameters. After further adjustment for ABI <0.9 and brachial-ankle pulse wave velocity, the relation remained significant to overall mortality (HR, 2.91; 95% CI, 1.28-6.64; P=0.01) and cardiovascular mortality (HR, 3.15; 95% CI, 1.05-9.44; P=0.04). CONCLUSIONS A difference in systolic BP of ≥15 mmHg or diastolic BP of ≥10 mmHg between legs was associated with peripheral vascular disease and increased risk for overall and cardiovascular mortality in hemodialysis patients. Detection of an interleg BP difference may identify hemodialysis patients at increased risk of peripheral vascular disease and overall and cardiovascular mortality.

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m2/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD.

Association of hsCRP, White Blood Cell Count and Ferritin with Renal Outcome in Chronic Kidney Disease Patients

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope<-6 ml/min/1.73 m2/y) in 3303 patients with stage 3–5 CKD. In all subjects, the mean hsCRP, WBC count, and ferritin levels were 1.2 (0.4, 5.4) mg/L, 7.2±2.3×103 cells/µL, and 200 (107,349) ng/mL, respectively. During a mean 3.2-year follow-up, there were 1080 (32.7%) subjects commencing RRT, and 841(25.5%) subjects presenting rapid renal progression. Both hsCRP and ferritin were associated with increased risk for RRT with the adjusted HR (tertile 3 versus tertile 1∶1.17 〔1.01–1.36〕 and 1.20 〔1.03–1.40〕, respectively). Both hsCRP and ferritin were associated with increased odds for rapid renal progression with the adjusted OR (tertile 3 versus tertile 1∶1.40 〔1.13–1.77〕 and 1.32 〔1.06–1.67〕, respectively). hsCRP and ferritin stratified by albumin were also associated with RRT and rapid renal progression. Instead, WBC count was not associated with renal outcome. In conclusion, elevated levels of hsCRP and ferritin are risk factors associated with RRT and rapid renal progression in advanced CKD patients.

Ratio of transmitral E-wave velocity to early diastole mitral annulus velocity with cardiovascular and renal outcomes in chronic kidney disease.

Background/Aims: Impaired left ventricular diastolic function and increased left ventricular filling pressure are frequently noted in patients with chronic kidney disease (CKD), even in early stages. The association of increased left ventricular filling pressure with cardiovascular and renal outcomes remains uncertain in CKD. This study is designed to assess whether the ratio of transmitral E-wave velocity (E) to early diastole mitral velocity (Ea) is associated with cardiovascular events and progression to dialysis in patients with CKD stages 3-5. Methods: This longitudinal study enrolled 356 predialysis CKD patients. Cardiovascular events were defined as cardiovascular death, hospitalization for unstable angina, nonfatal myocardial infarction, ventricular tachycardia, hospitalization for congestive heart failure, transient ischemia attack, and stroke. The renal endpoint was defined as commencement of dialysis. The relative cardiovascular events and renal endpoints risks were analyzed by Cox regression methods. Results: The high E/Ea was independently associated with old age, cerebrovascular disease, congestive heart failure, high systolic blood pressure, hypertriglyceridemia, low hemoglobin, proteinuria, and worse echocardiographic profiles. Besides, the high E/Ea increased the risk of cardiovascular events (hazard ratio (HR) 1.067; 95% confidence interval (CI) 1.017-1.119; p = 0.008) and progression to dialysis (HR 1.042; 95% CI 1.000-1.085; p = 0.048). Conclusions: Our study in patients of CKD stages 3-5 demonstrated the high E/Ea was associated with increased cardiovascular events and progression to dialysis. Assessment of the E/Ea by Doppler echocardiography is useful for predicting the risk of adverse cardiovascular and renal outcomes in CKD patients.