High Levels of Serum Triglycerides Associated with Incidence and Progression of CKD

Journal of Renal Nutrition. 2107;27(6):381-394

There are few data available on the association of serum triglycerides (TGs) and consumption of alcohol with chronic kidney disease (CKD). Kazuhiko Tsuruya, MD, PhD, and colleagues conducted a longitudinal cohort study designed to examine the association of TGs and alcohol consumption with CKD in the general population.

Study participants (n=47,737 men and 69,542 women) were stratified to quartiles according to serum TG levels. The primary outcome measures of interest were annual changes in estimated glomerular filtration rate (eGFR) in all participants, incident CKD in participants without CKD, and progression of CKD in participants with CKD. The association of alcohol consumption with those factors and whether daily consumption of alcohol alters the association of serum TG with renal prognosis was also examined.

In all participants during the 2-year study period, there was a significant association between a greater decline in eGFR and higher serum TG; the association remained significant after adjustment for confounding factors. There was also a significant association with serum TG and the incidence and progression of CKD following 2 years in participants with and without CKD at baseline, respectively. In analysis stratified by alcohol consumption status, the association between high TG and eGFR and CKD was modified with daily alcohol consumption.

In summary, the researchers said, “Elevated serum TG was associated with the decline in eGFR and the incidence and progression of CKD. In addition, these associations were modified by daily alcohol consumption.”

 

Prasugrel versus Clopidogrel in Patients with CKD

JACC: Cardiovascular Interventions. doi: 10.1016/j.jcin.2017.02.047

The PROMETHEUS study was a multicenter observational study that compared outcomes with prasugrel versus clopidogrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Results were reported by Usman Baber, MD and colleagues.

The cohort was stratified by chronic kidney disease (CKD) status. Major cardiac events at 90 days and at 1 year were defined as a composite of death, myocardial infarction, or unplanned revascularization. Clinically significant bleeding was defined as bleeding that required transfusion or hospitalization.

The total cohort included 19,832 patients; of those, 28.3% had CKD and 71.7% did not have CKD. Patients with CKD were older and had greater comorbidities, including diabetes and multivessel diseases. Compared with non-CKD patients, prasugrel was prescribed less often to those with CKD (24.0% vs 11.0%, respectively; P<.001).

At 1 year, there was an association between CKD and higher adjusted risk of major adverse cardiac events (1.27; 95% confidence interval [CI], 1.18-1.37) and bleeding (1.46; 95% CI, 1.24-1.73). In both the CKD and non-CKD cohorts, unadjusted rates of major adverse cardiac events at 1 year were lower with prasugrel versus clopidogrel (18.3% vs 26.5%; P<.001) and non-CKD (10.9% vs 17.9%; P<.001); those associations were attenuated following propensity stratification. Unadjusted differences in bleeding at 1 year with prasugrel versus clopidogrel (6.9% vs 7.4%; P=.18 in the CKD group; 2.6% vs 3.5%; P=.008 in the non-CKD group) were no longer significant following propensity score adjustment.

“Although risks for 1-year major adverse cardiac events were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairments. Irrespective of CKD status, outcomes associated with prasugrel were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS,” the researchers said.

 

CKD and ESRD Associated with Worse In-Hospital Outcomes in Patients Undergoing TAVR

JACC: Cardiovascular Interventions. Doi:10.1016/j.jcin.2017.07.044

Tanush Gupta, MD, and colleagues reported results of a study designed to examine the association between chronic kidney disease (CKD) and in-hospital outcomes of transcatheter aortic valve replacement (TAVR). Previous studies have shown that CKD is a risk factor for worse outcomes following surgical aortic valve replacement (SAVR) but data on outcomes of patients with CKD undergoing TAVR are limited, particularly among patients on chronic dialysis.

Data from the 2012 to 2014 National Inpatient Sample database were utilized to identify all patients ≥18 years of age who underwent TAVR. Patients with no CKD, CKD without chronic hemodialysis, or end-stage renal disease (ESRD) on long-term dialysis were identified using International Classification of Diseases, Ninth Revision-Clinical Modification codes.

A total of 41,025 patients underwent TAVR from 2012 to 2014; of those, 62.4% (n=25,585) had no CKD, 33.5% (n=13,750) had CKD, and 4.1% (n=1690) had ESRD. Compared with patients without CKD, in-hospital mortality was significantly higher in patients with CKD or ESRD (3.8% vs 4.5% vs 8.3%, respectively). Using no CKD as reference, adjusted odds ratio for CKD was 1.39 (95% confidence interval [CI], 1.24-1.55) and for ESRD, 2.58 (95% CI, 2.09-3.13).

The incidence of major adverse cardiovascular events, defined as a composite of death, myocardial infarction, or stroke; net adverse cardiovascular events (composite of major adverse cardiovascular events, major bleeding, or vascular complications); and pacemaker implantation was higher in patients with CKD and with ESRD, compared with patients without AKD.

There were associations between acute kidney injury (AKI) and AKI that required dialysis, with 7-fold higher risk-adjusted in-hospital mortality in patients in both the CKD and non-CKD groups. There was no decline in the incidence of AKI and AKI requiring dialysis during the study period.

In conclusion, the researchers said, “Patients with CKD or ESRD have worse in-hospital outcomes after TVAR. AKI is associated with higher in-hospital mortality in patients undergoing TAVR and the incidence of AKI has not declined over the years.”

 

DIALYSIS

Outcomes Associated with Dialysis Following Transcatheter Valve Replacement

JACC: Cardiovascular Interventions. doi.10.1016/j.jcin.2017.05.020

Transcatheter valve replacement (TAVR) is an alternative to surgical aortic valve replacement; however, there are few data on the impact of dialysis on outcomes following TAVR. Charles J. Ferro, MD, and colleagues recently conducted a study designed to examine the risk factors for dialysis following TAVR; the study also compared TAVR prior to dialysis with TAVR following dialysis and the impact on mortality.

Data on 6464 patients in the UK Transcatheter Aortic Valve Implantation Registry were prospectively gathered. The patients underwent TAVR in the United Kingdom from 2007 to 2014; median follow-up was 625 days.

During the study period, the proportion of patients on dialysis prior to TAVR remained constant (1.8%). In 2007-2008, the proportion of patients newly requiring dialysis following TAVR was 6.1%, compared with 2.3% in 2013-2014. There was an independent association between the risk of new dialysis requirement following TAVR and lower renal function at baseline, year of procedure, impaired left ventricular function, diabetes, use of an Edwards valve, a nontransfermoral approach, the need for open surgery, and moderate-to-severe aortic regurgitation following the procedure.

There was an association between the need for new dialysis after TAVR and higher mortality after 30 days (hazard ratio [HR], 6.44; 95% confidence interval [CI], 4.878.53; P<.001). The association remained at 4 years (HR, 3.54; 95% CI, 2.99-4.19; P<.001), compared with patients who did not require dialysis.

In conclusion, the researchers said, “The proportion of patients needing dialysis after TAVR has decreased over time. Post-TAVR dialysis is associated with increased mortality, Factors identified with dialysis requirement after TAVR require further investigation.”

 

Nutritional Competence Score and Risk of Death in Hemodialysis Patients

Journal of Renal Nutrition. doi.org/10.1053/j.jrn.2017.06.006

In patients on hemodialysis, the new Nutritional Competence Score (NCS) has been shown to be associated with hospitalization and outcomes. The score includes measurements of serum albumin, creatinine, phosphate, equilibrated normalized protein catabolic rate, and interdialytic weight gain. Xiaoling Ye, MPH, and colleagues conducted a study designed to examine the dynamics, individual components, and the impact of hospitalizations on the trajectory of the NCS in the year prior to death. The study also examined whether dynamics in the NCS could provide additional independent prognostic value compared with a single cross-sectional assessment.

All Fresenius Medical Care North American patients who initiated hemodialysis between January 1, 2006, and December 31, 2011, and who had data on all five NCS components in at least 1 month were included in the study. NCS was quantified monthly. Comparisons of trajectories of nonsurvivors with those of survivors were made across varying strata of dialysis vintage. Survivors and nonsurvivors were matched according to dialysis vintage. Cox proportional hazards models were used to assess the association of NSC at baseline and NCS dynamics with risk of mortality.

The study cohort included 110,794 patients. Of those, across all dialysis vintage groups, patients who died had lower NCS compared with patients who survived. In patients who died, NCS declined significantly prior to death; there was no decline in NCS in patients who survived. The rate of decline in NCS was not materially influenced by hospitalization in the months prior to death. In Cox models, NCS over time carried significant predictive power above a cross-sectional NCD assessment.

“There are distinct differences in NCS values and their trajectories between patients who die and vintage-matched controls. These differences may be able to be exploited for implementation of a routine, prospective monitoring tool for early detection of patients at increased risk of death. Prospective studies are required to validate such an approach,” the researchers said.

 

END-STAGE RENAL DISEASE

Direct-Acting Antiviral Agents for Treatment of ESRD Patients with HCV

Hemodialysis International. doi: 10.111/hdi.12604

Patients with end-stage renal disease (ESRD) and hepatitis C virus (HCV) are at increased risk for mortality compared with those without HCV. Direct-acting antiviral agents (DAAs) have recently been approved for the management of HCV; ledipasvir in combination with sofosbuvir has been approved for the management of genotype 1 infection in patients with estimated glomerular filtration rate ≥30 mL/min/1.73 m2. There are few data on the role of these DAAs in management of patients on dialysis.

Mandarapu Surendra, MD, and colleagues conducted a single-center, prospective, open-label observational study designed to examine the safety and efficacy of ledipasvir and sofosbuvir in patients on hemodialysis diagnosed with HCV genotype 1 infection. Twenty-one patients were treated the ledipasvir and sofosbuvir. Of those, two patients died during the study (not related to therapy). All of the remaining 19 patients achieved sustained virologic response at 12 weeks (SVR12). There were no discontinuations or severe adverse drug effects during the study period. One patient experienced headache and another had giddiness; both were managed symptomatically.

In conclusion, the researchers said, “Ledipasvir and sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.”

 

TRANSPLANTATION

Biomarkers for Adverse Outcomes in Transplant Recipients

American Journal of Transplantation. 2017;17(9):2390-2399

In nontransplant populations, the filtration markers cystatin C and beta-2 microglobulin (B2M) are associated with adverse outcomes; the associations have been shown to be stronger than those with creatinine. M. C. Foster, MD, and colleagues conducted a study designed to examine the associations of estimated glomerular filtration rate from cystatin C (eGFRcyc), B2M (eGFRB2M), and creatinine (eGFRcr) with various clinical outcomes (cardiovascular, mortality, and kidney failure).

The study was a case-cohort model nested within the FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) trial. Study participants were stable kidney transplant recipients.

For the current study, 508 FAVORIT participants were randomly selected with enrichment for cardiovascular events (n=306; 54 within the subcohort), and mortality (n=208; 68 within in the subcohort). Mean age was 51.6 years, median transplant vintage was 4 years, 38% were women, and 23.6% were of a nonwhite race. Mean eGFRcyc was 46.0 mL/min/1.73 m2, mean eGFRcys was 43.8 mL/min/1.73 m2, and mean eGFRB2M was 48.8 mL/min/1.73 m2.  

Following multivariable adjustment, hazard ratios [HRs] for cardiovascular events for eGFRcyc and eGFRB2M <30 compared with ≥60 mL/min/1.73 m2 were 2.02 (95% confidence interval [CI], 1.09-3.76; P=.03) and 2.56 (95% CI, 1.35-4.88; P=.004), respectively. The HRs for mortality were 3.92 (95% CI, 2.11-7.31; P<.001) and 4.09 (95% CI, 2.21-7.54; P<.001), respectively. Finally, the HRs for kidney failure were 9.49 (95% CI, 4.28-21.00; P<.001) for eGFRcyc and 15.53 (95% CI, 6.99-34.51; P<.001) for eGFRB2M. Following additional adjustment for baseline eGFRcr, the associations persisted.

“We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in kidney transplant recipients,” the researchers said.

 

Social Network Participation Aids in Completion of Transplant Steps

American Journal of Transplantation. 2017;17(9):2400-2409

A study conducted at a new hemodialysis clinic by Avrum Gillespie, MD, and colleagues modeled the association between participation in a social network and kidney transplantation. Data (survey and observational) collected between August 2012 and February 2015 were utilized to examine the formation of a social network among 46 hemodialysis patients in a newly opened clinic. Of the 46 patients, 70% (n=32) formed a social network with other patients. The group discussed health (59%) and transplantation (44%) with other patients.

Transplant-eligible women participated in the network less often than men (56% vs 90%, P=.02); however, women who did participate discussed their health more often than men (90% vs 45.5%, P=.02). Compared with a median of 0 in the non-network group, those in the social network completed a median of two steps toward transplantation (P=.03). If the social networks were closely connected, the patients completed more steps; in addition, if members of the network completed more steps, other network members also completed more steps.

In conclusion, the researchers said, “The hemodialysis clinic patient social network had a net positive effect on completion of transplant steps, and patients who interacted with each other completed a similar number of steps.”