Fibrate and the risk of cardiovascular disease among moderate chronic kidney disease patients with primary hypertriglyceridemia.

Introduction: Hypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents. Methods: This study enrolled patients newly diagnosed CKD3 with LDL-C<100mg/dL and had never received statin or other lipid-lowering agents from Chang Gung Research Database. The participants were categorized into 2 groups based on the use of fibrate: fibrate group and non-fibrate group (triglyceride >200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics. Results: Compared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups. Conclusion: This study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events.

Can Concurrent Fibrate Use Reduce Cardiovascular Risks among Moderate Chronic Kidney Disease Patients Undergoing Statin Therapy? A Cohort Study.

The role of fibrates in treating hypertriglyceridemia in chronic kidney disease (CKD) patients to prevent cardiovascular disease (CVD) has been insufficiently investigated. Since statin is considered the first-line treatment for dyslipidemia in CKD patients, this study aims to evaluate the role of concurrent fibrate therapy with statins among moderate CKD patients. We recruited CKD3 patients from the Chang Gung Research Database who were receiving statin treatment but had not previously been administered ezetimibe or niacin. The participants were divided into two groups based on their use of fibrates (fibrate group) or those with triglyceride levels >200 mg/dL without fibrate treatment (non-fibrate group). The fibrate group (n = 954) only exhibited a significantly lower incidence of AMI (4.4% vs. 5.4%, HR: 0.77, 95% CI: 0.61 to 0.98). The risk of major adverse cardiovascular and cerebrovascular events (14.7% vs. 15.6%, HR: 0.91, 95% CI: 0.72 to 1.15) and all-cause mortality (5.7% vs. 6.1%, HR: 0.91, 95% CI: 0.63 to 1.30) did not significantly differ between the fibrate group and the non-fibrate group (n = 2358). In moderate CKD patients, combining fibrate therapy with statins may not offer additional cardiovascular protection compared to statin alone.

Use of fibrates is not associated with reduced risks of mortality or cardiovascular events among ESRD patients: A national cohort study.

Background: Although a recent study reported that fibrates are associated with a low risk of cardiovascular (CV) death and can postpone the need for long-term hemodialysis in patients with advanced chronic kidney disease (CKD), little is known regarding whether the CV protective effects of fibrates extend to patients with end-stage renal disease (ESRD). The present study compared CV outcomes and mortality among patients with ESRD treated with fibrates, statins, neither, or their combination. Methods: This cohort study extracted data from Taiwan's National Health Insurance Research Database (NHIRD). Adult patients with ESRD and hyperlipidemia were identified and categorized into four groups (fibrate, statin, combination, and non-user groups) according to their use of different lipid-lowering therapies within 3 months prior to the commencement of permanent dialysis. Inverse probability of treatment weighting was used to balance the baseline characteristics of the groups. The follow-up outcomes were all-cause mortality, CV death, and major adverse cardiac and cerebrovascular events (MACCEs). Results: Compared with the non-user and statin groups, the fibrate group did not exhibit significantly lower risks of all-cause mortality [fibrate vs. non-user: hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.92-1.03; statin vs. fibrate: HR, 0.95; 95% CI, 0.90-1.01], CV death (fibrate vs. non-user: HR, 0.97; 95% CI, 0.90-1.05; statin vs. fibrate: HR, 0.97; 95% CI, 0.90-1.06), and MACCEs (fibrate vs. non-user: HR, 1.03; 95% CI, 0.96-1.10; statin vs. fibrate: HR, 0.94; 95% CI, 0.87-1.004). The combination of fibrates and statins (specifically moderate- to high-potency statins) did not result in lower risks of all-cause mortality, CV death, or MACCEs compared with statins alone. Conclusion: In patients with ESRD, the use of fibrates might be not associated with reduced mortality or CV risks, regardless of whether they are used alone or in combination with statins.

Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients.

Background: Rigid dietary controls and pill burden make a very-low protein (0.3−0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41−0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

Supplementation with Folic Acid and Cardiovascular Outcomes in End-Stage Kidney Disease: A Multi-Institution Cohort Study.

BACKGROUND: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. METHODS: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. RESULTS: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. CONCLUSION: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.

Association of Low-Density Lipoprotein Cholesterol Levels During Statin Treatment With Cardiovascular and Renal Outcomes in Patients With Moderate Chronic Kidney Disease.

Background The benefit of low-density lipoprotein cholesterol (LDL-C) levels in chronic kidney disease populations remains unclear. This study evaluated the cardiovascular and renal outcomes in patients with stage 3 chronic kidney disease with different LDL-C levels during statin treatment. Methods and Results There were 8500 patients newly diagnosed as having stage 3 chronic kidney disease under statin treatment who were identified from the Chang Gung Research Database and divided into 3 groups according to their first LDL-C level after the index date: <70 mg/dL, 70 to 100 mg/dL, and >100 mg/dL. Inverse probability of treatment weighting was performed to balance baseline characteristics. Compared with the LDL-C ≥100 mg/dL group, the 70≤LDL-C<100 mg/dL group exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (6.8% versus 8.8%; subdistribution hazard ratio [SHR], 0.76 [95% CI, 0.64-0.91]), intracerebral hemorrhage (0.23% versus 0.51%; SHR, 0.44 [95% CI, 0.25-0.77]), and new-onset end-stage renal disease requiring chronic dialysis (7.6% versus 9.1%; SHR, 0.82 [95% CI, 0.73-0.91]). By contrast, the LDL-C <70 mg/dL group exhibited a marginally lower risk of major adverse cardiac and cerebrovascular events (7.3% versus 8.8%; SHR, 0.82 [95% CI, 0.65-1.02]) and a significantly lower risk of new-onset end-stage renal disease requiring chronic dialysis (7.1% versus 9.1%; SHR, 0.76 [95% CI, 0.67-0.85]). Conclusions Among patients with stage 3 chronic kidney disease, statin users with 70≤LDL-C<100 mg/dL and with LDL-C <70 mg/dL had similar beneficial effect in the reduction of risks of major adverse cardiac and cerebrovascular events and new-onset end-stage renal disease compared with those with LDL-C >100 mg/dL. Moreover, the 70≤LDL-C<100 mg/dL group seemed to have a lowest risk of intracerebral hemorrhage, although the incidence was low.

Prognostic Performance of Existing Scoring Systems among Critically Ill Patients Requiring Continuous Renal Replacement Therapy: An Observational Study.

BACKGROUND: Among critical patients, few studies have evaluated the discrimination of current illness scoring systems in predicting outcomes after continuous renal replacement therapy (CRRT) initiation. METHODS: Patients receiving CRRT in the ICU between 2005 and 2018 from the Chang Gung Research Database were extracted. All the components of the Acute Physiology Assessment and Chronic Health Evaluation (APACHE) III, Sequential Organ Failure Assessment (SOFA), qSOFA, and MOSAIC scoring systems on days 1, 3, and 7 of CRRT were recorded. Patients older than 80 years were identified and analyzed separately. RESULTS: We identified 3370 adult patients for analysis. The discrimination ability of the scoring systems was acceptable at day 7 after CRRT initiation, including SOFA (area under the receiver operating characteristic curve, 74.1% (95% confidence interval, 71.7-76.5%)), APACHEIII (74.7% (72.3-77.1%)), and MOSAIC (71.3% (68.8%-73.9%)). These systems were not ideal on days 1 and 3, and that of qSOFA was poor at any time point. The discrimination performance was slightly better among patients ≥80 years. CONCLUSIONS: APACHE III, MOSAIC, and SOFA can be intensivists and families' reference to make their decision of withdrawing or withholding CRRT after a short period of treatment, especially in adults ≥80 years old.

Assessment of Cardiopulmonary Bypass Duration Improves Novel Biomarker Detection for Predicting Postoperative Acute Kidney Injury after Cardiovascular Surgery.

Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.

Association between initial dialytic modalities and the risks of mortality, infection death, and cardiovascular events: A nationwide population-based cohort study.

To date, few studies have been conducted to pairwise compare the prognosis of peritoneal dialysis (PD), unplanned PD, and unplanned hemodialysis (HD). We analyzed longitudinal data from Taiwan's National Health Insurance Research Database. We included 45,165 patients whose initial dialytic modality was PD or unplanned HD between January 1, 2001 and December 31, 2013. We divided the patients into three groups according to their initial dialytic modalities. The primary outcomes were all-cause mortality and death from infection during 1-year follow up. The risks of all-cause mortality and infection death were higher in the unplanned PD group than in the planned PD group (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.28-1.60; HR 1.54, 95% CI 1.32-1.80). Likewise, the risks of all-cause mortality and infection death were higher in the unplanned HD group (HR 1.64, 95% CI 1.48-1.82; HR 1.85, 95% CI 1.61-2.13). Furthermore, the risks of all-cause mortality and infection death were also higher in the unplanned HD group than in the unplanned PD group (HR 1.15, 95% CI 1.07-1.23; HR 1.20, 95% CI 1.09-1.32). In conclusion, our study demonstrates that patients whose initial modality was planned PD or unplanned PD may have better clinical outcomes than those whose initial modality was unplanned HD.