Mei-Chuan Kuo

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.

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.

Impact of renal failure on the outcome of dengue viral infection.

BACKGROUND AND OBJECTIVES In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. RESULTS From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. CONCLUSIONS The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m2/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.

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.

Association of prescribed Chinese herbal medicine use with risk of end-stage renal disease in patients with chronic kidney disease

The evidence on whether Chinese herbal medicines affect outcome in patients with chronic kidney disease (CKD) is limited. Here we retrospectively explored the association of prescribed Chinese herbal medicine use and the risk of end-stage renal disease (ESRD) in patients with CKD. Patients with newly diagnosed CKD in the Taiwan National Health Insurance Research Database from 2000 to 2005 were categorized into new use or nonuse of prescribed Chinese herbal medicine groups. These patients were followed until death, dialysis initiation, or till the end of 2008. Among the 24,971 study patients, 11,351 were new users of prescribed Chinese herbal medicine after CKD diagnosis. Overall, after adjustment for confounding variables, the use group exhibited a significant 60% reduced ESRD risk (cause-specific hazard ratio 0.41, 95% confidence interval 0.37-0.46) compared with the nonuse group. The change was significantly large among patients using wind dampness-dispelling formulas (0.63, 0.51-0.77) or harmonizing formulas (0.59, 0.46-0.74), suggesting an independent association between specific Chinese herbal medicines and reduced ESRD risk. The findings were confirmed using propensity score matching, stratified analyses, and three weighting methods. However, dampness-dispelling and purgative formulas were associated with increased ESRD risk. Thus, specific Chinese herbal medicines are associated with reduced or enhanced ESRD risk in patients with CKD.

Hypokalemia, Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease

Background In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. Design, Participants & Measurements 2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. Results The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m2. Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19–2.35) in sK = 3.5–4 mEq/L, respectively, compared with sK = 4.5–5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. Conclusion In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.

Predicting Mortality of Incident Dialysis Patients in Taiwan - A Longitudinal Population-Based Study

Background Comorbid conditions are highly prevalent among patients with end-stage renal disease (ESRD) and index score is a predictor of mortality in dialysis patients. The aim of this study is to perform a population-based cohort study to investigate the survival rate by age and Charlson comorbidity index (CCI) in incident dialysis patients. Methods Using the catastrophic illness registration of the Taiwan National Health Insurance Research Database for all patients from 1 January 1998 to 31 December 2008, individuals newly diagnosed with ESRD and receiving dialysis for more than 90 days were eligible for our study. Individuals younger than 18 years or renal transplantation patients either before or after dialysis were excluded. We calculated the CCI, age-weighted CCI by Deyo-Charlson method according to ICD-9 code and categorized CCI into six groups as index scores <3, 4–6, 7–9, 10–12, 13–15, >15. Cox regression models were used to analyze the association between age, CCI and survival, and the risk markers of survival. Results There were 79,645 incident dialysis patients, whose mean age (± SD) was 60.96 (±13.92) years; 51.43% of patients were women and 51.2% were diabetic. In cox proportional hazard models and stratifying by age, older patients had significantly higher mortality than younger patients. The mortality risk was higher in persons with higher CCI as compared with low CCI. Mortality increased steadily with higher age or comorbidity both for unadjusted and for adjusted models. For all age groups, mortality rates increased in different CCI groups with the highest rates occurring in the oldest age groups. Conclusions Age and CCI are both strong predictors of survival in Taiwan. The older age or higher comorbidity index in incident dialysis patient is associated with lower long-term survival rates. These population-based estimates may assist clinicians who make decisions when patients need long-term dialysis.

High cost and low survival rate in high comorbidity incident elderly hemodialysis patients.

Background The comorbidity index is a predictor of mortality in dialysis patients but there are few reports for predicting elderly dialysis mortality and national population-based cost studies on elderly dialysis. The aim of this study was to evaluate the long-term mortality of incident elderly dialysis patients using the Deyo - Charlson comorbidity index (CCI) and to assess the inpatient and outpatient visits along with non-dialysis costs. Methods Data were obtained from catastrophic illness registration of the Taiwan National Health Insurance Research Database. Incident elderly dialysis patients (age >75 years) receiving hemodialysis for more than 90 days between Jan 1, 1998, and dec 31, 2007, were included. Baseline comorbidities were determined one year prior to the first dialysis day according to ICD-9 CM codes. Survival time, mortality rate, hospitalization time, outpatient visit frequency, and costs were calculated for different age and CCI groups. Results In 10,759 incident elderly hemodialysis patients, hazard ratios for all-cause mortality were significantly increased in the different age groups (p < 0.001) and CCI patients (p < 0.001). Death rates increased with both increasing age and CCI score. High comorbidity incident hemodialysis and elderly patients were found to have increased length of hospital stay and total hospitalization costs. Conclusions This population-based cohort study indicated that both age and higher CCI values were predictors of survival in incident elderly hemodialysis. Increased costs and mortality rates were evident in the oldest patients and in those with high CCI scores. Conservative treatment might be considered in high comorbidity and low-survival rate end stage renal disease (ESRD) patients.