Chih-Cheng Hsu

Increased risk of mortality in the elderly population with late-stage chronic kidney disease: a cohort study in Taiwan

BACKGROUND Taiwan has the worlds highest incidence and second highest prevalence of end-stage renal disease (ESRD), particularly in older age groups. However, the transition from chronic kidney disease (CKD) to death or ESRD remains unclear. This study aimed to investigate the impact of late-stage CKD on all-cause and cause-specific mortality by identifying the CKD population. METHODS This was an observational cohort study (n = 35 529), mean age 75.7 years (SD = 5.3), of participants in the Elderly Health Examination Program (EHEP) in Kaohsiung City, Taiwan, between 2002 and 2004. Estimated glomerular filtration rate (eGFR) was calculated by the simplified modified diet in renal disease equation. Proportional hazard ratios (HR) of mortality associated with late-stage CKD were assessed by Cox regression. RESULTS The crude prevalence rate of CKD stages 3-5 was 39.4%; 1840 participants (5.18%) died within 2-year follow-up, a mortality rate of 20.3 per 1000 person-years overall and 16.4 per 1000 person-years in the reference group. Higher HR for all-cause and cause-specific mortality were found in the groups with decreased eGFR. Compared with the reference group (eGFR > 60 mL/min/1.73 m(2)), adjusted HR for all-cause mortality were 1.5, 2.1 and 2.6 for groups with eGFR 30-44, 15-29 and < 15 mL/min/ 1.73 m(2), respectively (P < 0.001). Higher HR of mortality due to cardiovascular or renal diseases were also significantly associated with decreased eGFR (P < 0.05). CONCLUSION Late-stage CKD is a significant risk factor for mortality, especially due to cardiovascular and renal diseases, in elderly Taiwanese. Given the higher prevalence rate of late-stage CKD in the study area, CKD patient mortality was relatively lower, which might reflect underestimation of renal function for patients at early stages of CKD, or partly explain the high ESRD population.

Association of dialysis with the risks of cancers.

Background To increase the survival span after dialysis in patients with end-stage renal disease (ESRD), identifying specific cancer risks is crucial in the cancer screening of these patients. The aim of this study was to investigate the risks of various cancers in an incident dialysis group in comparison with a non-dialysis group. Method We conducted a nationwide cohort study by using data from the Taiwan National Health Insurance Research Database. Patients who initially received long-term dialysis between January 1997 and December 2004, were selected and defined as the dialysis group and were matched with the non-dialysis patients (control group) according to age, sex, and index year. Competing risk analysis was used to estimate cumulative incidence and subdistribution hazard ratios (SHRs) of the first cancer occurrence. Results After consideration for the competing risk of mortality, the dialysis group showed a significantly higher 7-year cancer incidence rate than did the control group (6.4%; 95% confidence interval [CI], 6.0%-6.7% vs 1.7%; 95% CI, 1.4%-2.1%; P <0.001).The modified Cox proportional hazard model revealed that the dialysis group had significantly association with increased risks for all cancers (SHR, 3.43; 95% CI, 3.02-3.88). The risk of cancers was dominated in younger and female patients. Specific cancer risks were significantly higher in the dialysis group particularly in the development of oral, colorectal, liver, blood, breast, renal, upper urinary tract, and bladder cancer than in the control group. Multivariable stratified analyses confirmed the association between long-term dialysis and cancer in all subgroups of patients. Conclusions Dialysis is associated with a higher risk of cancer in patients with ESRD. However, cancer screening in ESRD population should be a selective approach, based on individual patient health condition and life expectancy.

Outcomes of overseas kidney transplantation in chronic haemodialysis patients in Taiwan

Aim:  Overseas kidney transplantation has often been reported to have unsatisfactory outcomes. This study aims to compare post‐transplantation outcomes between overseas and domestic kidney transplant (KT) recipients in Taiwan.

Add-on Protective Effect of Pentoxifylline in Advanced Chronic Kidney Disease Treated with Renin-Angiotensin-Aldosterone System Blockade - A Nationwide Database Analysis

A combination therapy of pentoxifylline with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) decreased proteinuria or glomerular filtration rate decline in early chronic kidney disease (CKD). Whether adding pentoxifylline to ACEI/ARB provides additional benefits on outcome is unclear in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND). A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 14,117 CKD 5 ND with serum creatinine levels >6 mg/dL and hematocrit levels <28% and who have been treated with ACEI/ARB. All patients were divided into pentoxifylline users and nonusers. Patient follow-up took place until dialysis, death before initiation of dialysis or December 31, 2009. Finally, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before dialysis. After propensity score-matching, use of pentoxifylline was associated with a lower risk for long-term dialysis or death in ACEI/ARB users (HR, 0.94; 95% CI, 0.90–0.99) or ARB users (HR, 0.91; 95% CI, 0.85–0.97). In conclusion, pentoxifylline exhibited a protective effect in reducing the risk for the composite outcome of long-term dialysis or death in ACEI/ARB treated CKD 5 ND.

High Uric Acid Ameliorates Indoxyl Sulfate-Induced Endothelial Dysfunction and Is Associated with Lower Mortality among Hemodialysis Patients

High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6.1 mg/dL was associated with a higher risk of all-cause mortality compared with a UA level of >8.1 mg/dL [HR, 1.20, 95% CI (1.10–1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of <6.1 mg/dL was associated with greater risks of cardiovascular mortality [HR, 1.26, 95% CI (1.13–1.41)] and stroke-related mortality [HR, 1.59, 95% CI (1.12–2.25)], respectively. In vitro experiments further showed an increase in oxidative stress and an inhibition nitric oxide synthesis by indoxyl sulfate (IS) in human aortic endothelial cells, which were significantly attenuated by UA in a dose-dependent manner. We concluded that higher UA in serum was associated with lower risk of all-cause and cardiovascular mortality among HD patients probably through its antioxidant property in ameliorating the IS-related vascular toxicity.

Use of non-steroidal anti-inflammatory drugs and risk of chronic kidney disease in people with Type 2 diabetes mellitus, a nationwide longitudinal cohort study

To investigate the temporal relationship between non‐steroidal anti‐inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus.

Severe Decline of Estimated Glomerular Filtration Rate Associates with Progressive Cognitive Deterioration in the Elderly: A Community-Based Cohort Study

Cognitive dysfunction is closely related to aging and chronic kidney disease (CKD). However, the association between renal function changes and the risk of developing cognitive impairment has not been elucidated. This longitudinal cohort study was to determine the influence of annual percentage change in estimated glomerular filtration rate (eGFR) on subsequent cognitive deterioration or death of the elderly within the community. A total of 33,654 elders with eGFR measurements were extracted from the Taipei City Elderly Health Examination Database. The Short Portable Mental Status Questionnaire was used to assess their cognitive progression at least twice during follow-up visits. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for cognitive deterioration or all-cause mortality with the percentage change in eGFR. During a median follow-up of 5.4 years, the participants with severe decline in eGFR (>20% per year) had an increased risk of cognitive deterioration (HR, 1.33; 95% confidence interval [CI], 1.08–1.72) and the composite outcome (HR, 1.17; 95% CI, 1.03–1.35) when compared with those who had stable eGFR. Severe eGFR decline could be a possible predictor for cognitive deterioration or death among the elderly. Early detection of severe eGFR decline is a critical issue and needs clinical attentions.

Kidney disease progression in patients of upper tract urothelial carcinoma following unilateral radical nephroureterectomy

Abstract Objectives: To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline. Patients and methods: In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Grays competing risk regression accounting for death were used to model renal outcome. Results: UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p<0.001). In Cox proportional hazard model and Fine and Grays competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01–4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality. Conclusions: UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.

Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis

BACKGROUND AND OBJECTIVES Hydroxychloroquine is widely used in patients with rheumatoid arthritis. However, large-scale studies examining the long-term effects of hydroxychloroquine on the development of kidney disease in patients with rheumatoid arthritis are lacking. We aimed to assess the long-term association of hydroxychloroquine use with the risk of developing CKD in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted an observational cohort study for patients with newly diagnosed rheumatoid arthritis who were enrolled prospectively in Taiwans National Health Insurance Research Database between January 1, 2000 and December 31, 2013. We used multivariable Cox proportional hazard regression to analyze the association of hydroxychloroquine use with incident CKD. RESULTS A total of 2619 patients, including 1212 hydroxychloroquine users and 1407 hydroxychloroquine nonusers, were analyzed. Incident CKD was reported in 48 of 1212 hydroxychloroquine users and 121 of 1407 hydroxychloroquine nonusers. The incidence rate of CKD was lower in hydroxychloroquine users than in hydroxychloroquine nonusers (10.3 versus 13.8 per 1000 person-years). After multivariable adjustment, hydroxychloroquine users still had a lower risk of incident CKD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.90; P=0.01) than hydroxychloroquine nonusers. The lower risk of subsequent CKD development was dose dependent and consistent across subgroup analyses. CONCLUSIONS Hydroxychloroquine use in patients with newly diagnosed rheumatoid arthritis is associated with a significantly lower risk of incident CKD compared with in nonusers.

Angiotensin receptor blockers are associated with lower mortality than ACE inhibitors in predialytic stage 5 chronic kidney disease: A nationwide study of therapy with renin-angiotensin system blockade

Dual renin angiotensin system (RAS) blockade using angiotensin-receptor blockers (ARBs) in combination with angiotensin converting enzyme inhibitors (ACEIs) is reported to improve proteinuria in both diabetic and non-diabetic patients. However, its renoprotective effect and safety remain uncertain in patients with advanced chronic kidney disease (CKD). From January 1, 2000 through June 30, 2009, we enrolled 14,117 pre-dialytic stage 5 CKD patients with serum creatinine >6mg/dL and hematocrit <28% under the treatment with erythropoiesis stimulating agents and RAS blockade. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) against the commencement of long-term dialysis and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before progression to end-stage renal disease requiring dialysis. In comparison with the ARB-only users, dual blockade with ACEIs and ARBs was associated with a significantly higher risk of (1) death in all CKD patients (HR = 1.49, [95%CI, 1.30–1.71]; P = 0.02) and in diabetic subgroup (HR = 1.58, [95%CI, 1.34–1.86]; P = 0.02); (2) composite endpoint of long-term dialysis or death in diabetic subgroup (HR = 1.10, [95%CI, 1.01–1.20]; P = 0.04); (3) hyperkalemia-associated hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05–7.15]; P = 0.04). However, ACEIs users were associated with higher mortality than ARBs users in all CKD patients (HR = 1.17, [95%CI, 1.07–1.27]; P = 0.03) and in diabetic subgroup (HR = 1.32, [95%CI, 1.18–1.48]; P = 0.03). Monotherapy of RAS blockade, especially ARB, is more effective and safer than dual RAS blockade in pre-dialytic stage 5 CKD patients.