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.

Supplemented Low-Protein Diet May Delay the Need for Preemptive Kidney Transplantation: A Nationwide Population-Based Cohort Study.

BACKGROUND: Although several studies suggest the benefit of a low-protein diet supplemented with amino acids and keto acids (sLPD) in delaying the initiation of hemodialysis, evidence on whether these nutritional approaches could delay the timing of preemptive transplantation is lacking. METHODS: Retrospective nationwide cohort study, from Taiwan's National Health Insurance Research Database. Patients having undergone a first preemptive kidney transplantation between 2001 and 2017 were identified and divided into two groups according to the presence of sLPD treatment or not. The primary outcome was the time between the diagnosis of advanced CKD and transplantation. Secondary outcomes were post-transplantation adverse events. RESULTS: A total of 245 patients who received their first preemptive kidney transplantation were identified from the nationwide database; 63 of them had been on an sLPD prior to transplantation (sLPD group). The duration between the day of advanced CKD diagnosis and the day of transplantation was significantly longer in the sLPD group compared with the non-sLPD group (median duration: 345 vs. 220 days, p = 0.001). The risk of post-transplantation adverse events did not differ between the two groups. CONCLUSIONS: Within the limits of its observational, retrospective design, this is the first study to suggest that nutritional management with sLPDs can safely delay the timing of preemptive kidney transplantation.

Advanced Chronic Kidney Disease with Low and Very Low GFR: Can a Low-Protein Diet Supplemented with Ketoanalogues Delay Dialysis?

BACKGROUND: Previous studies have demonstrated that dietary therapy can delay the initiation of dialysis, but little research has investigated whether patients with very poor renal function would benefit from a dietary therapy. METHODS: This study was performed by using the Chang Gung Research Database (CGRD), which is based on the largest medical system in Taiwan. Patients with estimated glomerular filtration rates (eGFR) < 15 mL/min/1.73 m2 between 2001 and 2015 with more than 3 months of low-protein diet supplemented with ketoanalogues (sLPD) were extracted (Ketosteril group). We then assigned five patients without any sLPD to match one patient of the Ketosteril group (comparison group). Both groups were followed up for 1 year for the initiation of dialysis and rates of major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: The Ketosteril group (n = 547), compared with the comparison group (n = 2735), exhibited a lower incidence of new-onset dialysis (40.2% vs. 44.4%, subdistribution hazard ratio (SHR): 0.80, 95% confidence interval (CI): 0.70-0.91) and MACCEs (3.7% vs. 5.9%, HR: 0.61, 95% CI: 0.38-0.97). The beneficial effect of an sLPD did not differ in patients with a baseline eGFR < 5 mL/min/1.73 m2. CONCLUSION: Even among patients with extremely low eGFR, sLPD treatment can safely delay the need for dialysis.

Temporal trends of incident diabetes mellitus and subsequent outcomes in patients receiving kidney transplantation: a national cohort study in Taiwan.

BACKGROUND: Allograft kidney transplantation has become a treatment of choice for patients with end-stage renal disease (ESRD), and post-transplant diabetes mellitus (PTDM) has been associated with impaired patient and graft survival. Taiwan has the highest incidence and prevalence rates of ESRD with many recipients and candidates of kidney transplantation. However, information about the epidemiologic features of PTDM in Taiwan is incomplete. Therefore, we aimed to investigate the prevalence and incidence of PTDM with subsequent patient and graft outcomes. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), 3663 kidney recipients between 1997 and 2011 were enrolled. We calculated the cumulative incidences of diabetes mellitus (DM) after transplantation. Cox proportional hazards model with competing risk analysis was used to calculate the hazard ratio (HR) and 95% confidence intervals (CI) between three targeted groups (DM, PTDM, non-DM). The outcomes of primary interest were the occurrence of graft failure excluding death with functioning graft, all-cause mortality, death with functioning graft and major adverse cardiovascular events (MACE) including myocardial infarction (MI), cerebrovascular accident (CVA) and congestive heart failure (CHF). Subgroup analysis for graft failure excluding death with functioning graft, MACE and all-cause mortality was performed, and interaction between PTDM and recipient age was examined. RESULTS: Of 3663 kidney transplant recipients, 531 (14%) had pre-existing DM and 631 (17%) developed PTDM. Compared with non-DM group, the PTDM and DM groups exhibited higher risk of graft failure excluding death with functioning graft (PTDM: HR 1.65, 95% CI 1.47-1.85; DM: HR 1.33, 95% CI 1.18-1.50), MACE (PTDM: HR 1.51, 95% CI 1.31-1.74; DM: HR 1.64, 95% CI 1.41-1.9), all-cause mortality (PTDM: HR 1.79, 95% CI 1.59-2.01; DM: HR 2.03, 95% CI 1.81-2.18), and death with functioning graft (PTDM: HR 1.94, 95% CI 1.71-2.20; DM: HR 1.94, 95% CI 1.71-2.21). Both PTDM and DM groups had increased cardiovascular disease-related mortality (PTDM: HR 2.14, 95% CI 1.43-3.20, p < 0.001; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.002), cancer-related mortality (PTDM: HR 1.56, 95% CI 1.18-2.07, p = 0.002; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.027), and infection-related mortality (PTDM: HR 1.47, 95% CI 1.14-1.90, p = 0.003; DM: HR 2.25, 95% CI 1.77-2.84, p < 0.001) compared with non-DM group. The subgroup analyses showed that the add-on risks of MACE and mortality from PTDM were mainly observed in patients who were younger and those without associated comorbidities including atrial fibrillation, cirrhosis, CHF, and MI. Age significantly modified the association between PTDM and MACE (pinteraction < 0.01) with higher risk in recipients with PTDM aged younger than 55 years (adjusted HR 1.64, 95% CI 1.40-1.92, p < 0.001). A trend (pinteraction = 0.06) of age-modifying effect on the association between PTDM and all-cause mortality was also noted with higher risk in recipients with PTDM aged younger than 55 years. CONCLUSIONS: In the present population-based study, the incidence of PTDM peaked within the first year after kidney transplantation. PTDM negatively impacted graft and patient outcomes. The magnitude of cardiovascular and survival disadvantages from PTDM were more pronounced in recipients aged less than 55 years. Further trials to improve prediction of PTDM and to prevent PTDM are warranted.

Does a Supplemental Low-Protein Diet Decrease Mortality and Adverse Events After Commencing Dialysis? A Nationwide Cohort Study.

BACKGROUND: A beneficial effect of a ketoanalogue-supplemented low-protein diet (sLPD) in postponing dialysis has been demonstrated in numerous previous studies. However, evidence regarding its effect on long-term survival is limited. Our study assessed the long-term outcomes of patients on an sLPD after commencing dialysis. METHODS: This retrospective study examined patients with new-onset end-stage renal disease with permanent dialysis between 2001 and 2013, extracted from Taiwan's National Health Insurance Research Database. Patients who received more than 3 months of sLPD treatment in the year preceding the start of dialysis were extracted. The outcomes studied were all-cause mortality, infection rate, and major cardiac and cerebrovascular events (MACCEs). RESULTS: After propensity score matching, the sLPD group (n = 2607) showed a lower risk of all-cause mortality (23.1% vs. 27.6%, hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.70⁻0.84), MACCEs (19.2% vs. 21.5%, HR 0.86, 95% CI 0.78⁻0.94), and infection-related death (9.9% vs. 12.5%, HR 0.76, 95% CI 0.67⁻0.87) than the non-sLPD group did. CONCLUSION: We found that sLPD treatment might be safe without long-term negative consequences after dialysis treatment.

Does hepatitis C virus affect the reactivation of hepatitis B virus following renal transplantation?

BACKGROUND: Hepatitis B virus (HBV) is endemic in Taiwan. Transplantation followed by long-term immunosuppressive medications may precipitate HBV reactivation. Interference of hepatitis C virus (HCV) with HBV gene expression and replication has been confirmed in many studies involving non-transplant populations. This study investigates the incidence of HBV reactivation following renal transplantation and compares the clinical outcome, especially the liver outcome, of patients with or without HCV co-infection. METHODS: Fifty-one of 512 renal transplant recipients were positive for hepatitis B surface antigen before surgery, and were followed for 81.6+/-7.5 (4-120) months. Seventeen of 51 patients acquired HCV before transplantation and six patients acquired HCV after renal transplantation. RESULTS: At the end of this assessment, we had 28 patients who suffered HBV reactivation and another 23 patients who suffered no HBV reactivation. Initially, we found a significant difference of HCV carriage (P<0.05) between patients with (seven out of 28 or 25%) or without (21 out of 23 or 91.3%) HBV reactivation. Further inspection showed that 21 of the 28 patients without HCV co-infection and seven of the 23 patients with HCV co-infection suffered HBV reactivation. After comparison, we found a lower incidence of HBV reactivation in patients with HCV co-infection than in patients without HCV co-infection (P<0.05). In contrast to the latter, we found that patients with HCV co-infection suffering HBV reactivation tended to have a late onset of HBV reactivation (P<0.05). Otherwise, there was no difference in hepatitis severity, in terms of peak alanine aminotransferase, total bilirubin levels and hepatitis reactivation-related death, between these two groups of patients. Finally, a multivariable analysis also revealed that HCV carriage was indeed an independent variable leading to the reduced incidence of HBV reactivation in patients with HCV co-infection. CONCLUSION: HCV might affect the reactivation of HBV by decreasing the incidence or delaying the onset of HBV reactivation in renal transplant recipients carrying both HBV and HCV.