Wan-Chun Liu

Association of Hyperuricemia with Renal Outcomes, Cardiovascular Disease, and Mortality

BACKGROUND AND OBJECTIVES Hyperuricemia is an independent risk factor for mortality, cardiovascular disease, and renal disease in general population. However, the relationship between hyperuricemia with clinical outcomes in CKD remains controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study investigated the association between uric acid with all-cause mortality, cardiovascular events, renal replacement therapy, and rapid renal progression (the slope of estimated GFR was less than -6 ml/min per 1.73 m(2)/y) in 3303 stages 3-5 CKD patients that were in the integrated CKD care system in one medical center and one regional hospital in southern Taiwan. RESULTS In all subjects, the mean uric acid level was 7.9 ± 2.0 mg/dl. During a median 2.8-year follow-up, there were 471 (14.3%) deaths, 545 (16.5%) cardiovascular events, 1080 (32.3%) participants commencing renal replacement therapy, and 841 (25.5%) participants with rapid renal progression. Hyperuricemia increased risks for all-cause mortality and cardiovascular events (the adjusted hazard ratios for quartile four versus quartile one of uric acid [95% confidence interval] were 1.85 [1.40-2.44] and 1.42 [1.08-1.86], respectively) but not risks for renal replacement therapy (0.96 [0.79-1.16]) and rapid renal progression (1.30 [0.98-1.73]). CONCLUSIONS In stages 3-5 CKD, hyperuricemia is a risk factor for all-cause mortality and cardiovascular events but not renal replacement therapy and rapid renal progression.

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.

Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES Cardiac abnormalities were frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether echocardiographic parameters are associated with rate of renal function decline and progression to dialysis in CKD stage 3 to 5 patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal study enrolled 415 patients. The renal end point was defined as commencement of dialysis. The change in renal function was measured by estimated GFR (eGFR) slope. RESULTS Progression to dialysis was predicted by wide pulse pressure, low albumin, low hemoglobin, high calcium-phosphorous product, proteinuria, diuretics use, and concentric left ventricular hypertrophy (LVH) (hazard ratio, 2.03; 95% confidence interval [CI], 1.00 to 4.10; P = 0.05). The eGFR slope was negatively associated with total cholesterol, uric acid, proteinuria, diuretics use, and left atrial (LA) diameter (change in slope, -0.50; 95% CI, -0.89 to -0.11; P = 0.01) and positively associated with albumin and left ventricular ejection fraction (LVEF) (change in slope, 0.06; 95% CI, 0.03 to 0.08; P < 0.001). CONCLUSIONS Our study in patients of CKD stage 3 to 5 demonstrated that concentric LVH was associated with progression to dialysis, and that increased LA diameter and decreased LVEF were associated with faster renal function decline. Echocardiography may help identify high-risk groups with progressive decline in renal function to dialysis and rapid progression of renal dysfunction in CKD stage 3 to 5 patients.

Ankle brachial index as a predictor for mortality in patients with chronic kidney disease and undergoing haemodialysis.

Aim:  The ankle brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and haemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end‐stage renal disease. The aim of this study was to investigate the predictors for mortality by using ABI value in patients with CKD and undergoing haemodialysis in Taiwan.

Acute Renal Failure and Its Risk Factors in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Background: Skin lesion is the most frequent manifestation of adverse drug reactions. Drug-induced cutaneous hypersensitivity and drug-induced acute interstitial nephritis might share a similar mechanism involving drug-specific T cells. We thus investigated the renal outcome of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe drug-induced cutaneous hypersensitivity, and hypothesize that skin detachment in SJS/TEN might be associated with acute renal failure (ARF). Methods: 234 hospitalized patients were retrospectively classified into an SJS/TEN group (skin detachment) or an erythematous multiforme majus group (target-like exanthema alone). Results: Both drugs and chronic kidney disease (CKD) are associated with SJS/TEN. The SJS/TEN group was more likely to develop ARF than the erythematous multiforme majus group (18.8 vs. 4.3%, p < 0.05) despite similar initial creatinine clearance. In the ARF patients, RIFLE-F class, dialysis and long-term dialysis were 25, 15 and 5%, respectively. The offending drugs in ARF were also associated with CKD. Hyponatremia and late hypokalemia were more frequently in the SJS/TEN group (15.6 vs. 2.9%, 7.3 vs. 0.7%, respectively, p < 0.05). Sepsis, allopurinol, antibiotics, NSAIDs, CKD and hypoalbuminemia (OR: 18.8, 9.8, 10.1, 9.0, 5.3 and 3.3, respectively, p < 0.05) were the risk factors of developing ARF. Conclusion: ARF, the need for dialysis, and late hypokalemia could be the consequences of SJS/TEN. Skin detachment after certain medication might implicate the associated ARF, especially in CKD patients.

Early Nephrology Referral Is Associated With Prolonged Survival in Hemodialysis Patients Even After Exclusion of Lead-Time Bias

Background:Early nephrology referral (ER) has been suggested to lower morbidity and mortality in dialysis patients, but the nature of the association has been criticized as possibly because of lead-time bias. This study aims to evaluate if ER is associated with improved survival of hemodialysis patients when the lead-time bias is excluded. Methods:A total of 192 hemodialysis patients from a medical center and a regional hospital were enrolled in the period from January 1997 to December 2006. ER and late referral (LR) were defined as referral to nephrologists greater or less than 6 months, respectively, before the initiation of hemodialysis. Follow-up of clinical course in all patients was timed from the date at which estimate glomerular filtration rate was estimated to be 15 mL/min/1.73m2. The relative overall survival was analyzed by Cox-regression adjusted for their demographic and comorbid conditions Results:Compared with LR patients, ER patients were less likely to have hypoalbuminemia in the beginning of hemodialysis, more likely to have received erythropoietin or phosphate binder therapy, more likely to have a vascular access created before the first hemodialysis, and had a slower rate of renal function decline before hemodialysis. In multivariate analysis, LR (hazard ratio: 2.827; P = 0.049) and diabetes mellitus were both independently associated with increased mortality risk. The survival benefits of ER seem to be originated from the period before initiation of renal replacement therapy. Conclusions:Our findings show that ER is significantly associated with prolonged survival after exclusion of lead-time bias, which is consistent with ER being associated with better clinical outcomes in hemodialysis patients.

The ratio of observed to predicted left ventricular mass is independently associated with increased cardiovascular events in patients with chronic kidney disease.

A condition involving the growth of the myocardium that exceeds hemodynamic needs has been reported and called as inappropriate left ventricular mass (LVM). The appropriateness of LVM can be estimated by the ratio of observed LVM to predicted LVM. The excessive growth of LVM is frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether the ratio of observed to predicted LVM is a useful prognostic indicator of cardiovascular events in patients with moderate to advanced CKD. We consecutively enrolled 485 patients with CKD stages 3–5 from our Outpatient Department of Internal Medicine. Inappropriate LVM was defined as observed LVM more than 28% greater than the predicted value. The relative risk of cardiovascular events was analyzed by Cox-regression methods. There was a significant trend for a stepwise increase in the observed/predicted LVM ratio (P<0.001) and the prevalence of inappropriate LVM (P=0.003) corresponding to advances in CKD stages. In the multivariate analysis, old age, a history of coronary artery disease, congestive heart failure, atrial fibrillation, wide pulse pressure, decreased serum albumin and hemoglobin levels, left atrial diameter >4.7 cm and increased observed/predicted LVM were independently associated with increased cardiovascular events. Our findings show that increased observed/predicted LVM is independently associated with adverse cardiovascular outcomes in patients with CKD stages 3–5.

Determinants of Peripheral Arterial Stiffness in Patients with Chronic Kidney Disease in Southern Taiwan

High prevalences of peripheral artery occlusive disease (PAOD) and increased arterial stiffness have been reported in patients with chronic kidney disease (CKD). However, these have not been assessed in Taiwan where the prevalence of CKD is high. The aim of this study was to investigate the determinants of PAOD and arterial stiffness in patients with CKD in southern Taiwan. We enrolled 169 patients with stage 3–5 CKD in one regional hospital. Ankle‐brachial index (ABI) and brachial‐ankle pulse wave velocity were measured using an ABI‐form device (Colin VP1000). In multivariate analysis, ABI < 0.9 was positively correlated with the presence of diabetes mellitus (p = 0.014) and negatively correlated with the estimated glomerular filtration rate (eGFR) (p = 0.049), and increased brachial‐ankle pulse wave velocity was correlated with increased age, diabetes mellitus, increased systolic blood pressure, decreased pulse pressure and decreased eGFR. This study identified determinants of PAOD and arterial stiffness in patients with CKD in one hospital in southern Taiwan. In addition to the traditional atherosclerotic risk factors, decreased eGFR was also correlated with PAOD and increased arterial stiffness in these patients.

The rs1014290 Polymorphism of the SLC2A9 Gene Is Associated with Type 2 Diabetes Mellitus in Han Chinese

Aims. The SLC2A9 gene encodes the glucose transporter 9, with the abilities of transporting both glucose and uric acid and is involved in the pancreatic glucose-stimulated insulin secretion. The single nucleotide polymorphisms (SNPs) of SLC2A9 accounted for 5% variance of serum uric acid (UA). UA was identified as a risk factor for type 2 diabetes mellitus (DM). We investigated whether the SLC2A9 gene variations are associated with type 2 DM in Han Chinese. Methods. Three common SNPs of the SLC2A9, rs1014290, rs2280205, and rs3733591, were genotyped in 1003 Han Chinese randomly selected from Kaohsiung, Taiwan. Results. The variant SNP rs1014290 is associated with decreased 0.12-fold risk of type 2 DM (P = .002). Per-copy increase in the minor C-allele results in 0.13 mmol/L (P = .037) and 10.03 μmol/L (P = .016) decrease in serum glucose and UA, respectively. Conclusions. The SNP rs1014290 within the SLC2A9 gene is associated with type 2 DM in Han Chinese.

Stepwise Increases in Left Ventricular Mass Index and Decreases in Left Ventricular Ejection Fraction Correspond with the Stages of Chronic Kidney Disease in Diabetes Patients

Aims. Patients with diabetic nephropathy are reported to have a high prevalence of left ventricular structural and functional abnormalities. This study was designed to assess the determinants of left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF) in diabetic patients at various stages of chronic kidney disease (CKD). Methods. This cross-sectional study enrolled 285 diabetic patients with CKD stages 3 to 5 from our outpatient department of internal medicine. Clinical and echocardiographic parameters were compared and analyzed. Results. We found a significant stepwise increase in LVMI (P < 0.001), LVH (P < 0.001), and LVEF <55% (P = 0.013) and a stepwise decrease in LVEF (P = 0.038) corresponding to advance in CKD stages. Conclusions. Our findings suggest that increases in LVMI and decreases in LVEF coincide with advances in CKD stages in patients with diabetes.