March 2017: Abstract Roundup

Acute Kidney Injury 

AKI Associated with Long-Term Risk for Cardiovascular Events
Journal of the American Society of Nephrology. 2017;28(1):377-387

In a study designed to determine whether there is an association between acute kidney injury (AKI) and long-term cardiovascular disease, Ayodele Odutayo, MD, and colleagues performed a systematic review and meta-analysis of previous cohort studies. The studies of interest included adults with and without AKI and reported a multivariable-adjusted relative risk for an association between AKI and cardiovascular mortality; major cardiovascular events; and disease-specific events, including congestive heart failure, acute myocardial infarction, and stroke.

The review included 25 studies involving 254,408 adults; of those, 55,150 had AKI. AKI was associated with an 86% increased risk for cardiovascular mortality and a 38% increased risk for major cardiovascular events. For the disease-specific events, the increased risks were 58% for heart failure, 40% increased risk for acute myocardial infarction, and 15% increased risk for stroke. The increased risk of heart failure and myocardial infarction remained in subgroup analyses based on severity of AKI and proportion of adults with baseline ischemic heart disease.

“In conclusion, AKI associates with an elevated risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction,” the researchers said.

Chronic Kidney Disease 

Pro-ENK Level and Risk of CKD and Kidney Function Decline
Journal of the American Society of Nephrology. 2017;28(1):291-303

In acute settings, high levels of proenkephalin-A (pro-ENK) have been associated with decreased estimated glomerular filtration rate (eGFR). Researchers, led by Christina-Alexandra Schulz, MD, recently conducted a prospective cohort study to assess whether levels of pro-ENK predict chronic kidney disease (CKD) in 2568 participants without CKD at baseline. CKD was defined as eGFR >60 mL/min/1.73 m2.

Mean follow-up was 16.6 years. During that time, 31.7% of participants developed CKD. Those with baseline levels of pro-ENK in the highest tertile had significantly greater yearly mean decline in eGFR and rise of levels of cystatin C and creatinine. In addition, participants in the highest tertile of baseline pro-ENK had increased incidence of CKD in comparison with those in the lowest tertile, after adjusting for multiple factors.

The researchers said, “Circulating plasma pro-ENK levels predict incident CKD and may aid in identifying subjects in need of primary prevention regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time.”

Soluble Klotho Level and Kidney Function Decline
Journal of the American Society of Nephrology. doi:10.1681/ASN.2016080828

According to researchers, chronic kidney disease (CKD) appears to be a condition of soluble klotho deficiency, and there are known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis. There are few data regarding the longitudinal association between soluble klotho levels and changes in kidney function.

David A. Drew, MD, and colleagues recently assayed serum soluble a-klotho in 2496 participants of the Health Aging and Body Composition study, a study that included older adults, and evaluated the associations between soluble klotho levels and decline in kidney function and incident CKD.

Mean age of participants was 75 years, 52% were women, and 38% were black. Median klotho level was 630 pg/mL. Following adjustment for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism, each two-fold higher level of klotho was associated with lower odds of decline in kidney function (odds ratio, 0.78 for 30% decline in eGFR and 0.85 for >3 mL/min per year decline in eGFR). There was no association between a two-fold higher level of klotho and incident CKD (incident rate ratio, 0.90).

The researchers summarized by saying, “Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.”


Canagliflozin’s Renoprotective Effects Examined
Journal of the American Society of Nephrology. 2017;28(1):313-320

Previous studies have shown that sodium-glucose cotransporter 2 inhibition with canagliflozin decreased hemoglobin A1c (HbA1c), body weight, blood pressure, and albuminuria, suggesting a renal protective benefit. To determine whether canagliflozin decreases albuminuria and reduces decline in renal function independently of its glycemic effects, Hiddo J. Heerspink, MD, and colleagues recently conducted a secondary analysis of data from a clinical trial involving 1450 patients with type 2 diabetes receiving metformin. The patients were randomly assigned to receive once-daily canagliflozin 100 mg, once daily canagliflozin 300 mg, or glimepiride uptitrated to 6 to 8 mg.

At 2 years of follow-up, declines in estimated glomerular filtration rates were 3.3 mL/min/1.73 m2 per year, 0.5 mL/min/1.73 m2 per year, and 0.9 mL/min/1.73 m2 per year in the glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups, respectively (P<.01 for each canagliflozin group vs glimepiride). Patients in the glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg group had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year, and 0.55%, 0.65%, and 0.74%, respectively, at 2 years.

In conclusion, the researchers said, “Canagliflozin 100 or 300 mg per day, compared with glimepiride, slowed the progression of renal disease in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.”

End-Stage Renal Disease

Risk of ESRD and Intake of Red Meat Linked 
Journal of the American Society of Nephrology. 2017;28(1):304-312

Studies have demonstrated that restricting consumption of protein may slow the progression of chronic kidney disease to end-stage renal disease (ESRD); however, data are unclear on the effects of dietary protein intake level and the food sources of dietary protein on the risk of ESRD. Quan-Lan Jasmine Lew, MD, and colleagues recently examined those effects in the Singapore Chinese Health Survey, a prospective, population-based cohort of 63,257 adults ages 45 to 84 years in China; cohort recruitment occurred from 1993 to 1998.

Over a mean follow-up of 15.5 years, there were 951 cases of ESRD in the study cohort. Compared with the lowest tertile of total protein intake, those in the three higher tertiles combined had a hazard ratio (HR) for ESRD of 1.24; however, the dose-dependent association across the tertiles was not statistically significant. There was a strong association between intake of red meat and the risk of ESRD in a dose-dependent manner (HR for the highest quartile vs the lowest quartile, 1.40; P for trend<.001). There was no association between intake of poultry, fish, eggs, or dairy products with the risk of ESRD.

“Our study shows that red meat intake may increase the risk of ESRD in the general population and substituting alternative sources of protein may reduce the incidence of ESRD,” the researchers said.

Statins and Vascular Calcification
European Journal of Clinical Investigation. doi:10.1111/eci.12718

Coronary artery calcification (CAC) and inflammation are contributing factors in patients with end-stage renal disease (ESRD). Survival in patients with ESRD is not improved with statins, and the effect of statins on vascular calcification is not well documented. Zhimin Chen, MD, and colleagues recently conducted a study to examine associations between CAC, inflammatory biomarkers, statins, and mortality in patients with ESRD.

In 240 patients with ESRD from cohorts including 86 living donor kidney transplant recipients, 96 incident dialysis patients, and 58 prevalent peritoneal dialysis patients, the researchers analyzed associations of all-cause mortality with CAC score, interleukin-6 with high sensitivity C-reactive protein, and tumor necrosis factor, and use of statins.

Among the 240 patients, 53% (n=129) had a CAC score >100 Agatston units. In multivariate analysis, independent predictors of one-standard deviation higher CAC score were age, male sex, diabetes, and use of statins. Following adjustment for age, sex, diabetes, cardiovascular disease, use of statins, protein-energy wasting, and inflammation, the association between CAC score and mortality remained significant. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC.

In conclusion, the researchers said, “Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.”


Clot Structure May Be a Risk Factor for Mortality in Hemodialysis Patients
Journal of the American Society of Nephrology. doi:10.1681/ASN.2016030336

It is known that patients with chronic kidney disease on hemodialysis are at increased risk for cardiovascular disease. Cardiovascular events are associated with fibrin clot structure and clot lysis; however, there are few data on the influence of clot density on outcomes in patients on hemodialysis. Katharina Schuett, MD, and colleagues conducted a prospective cohort study to identify fibrin clot structure parameters and effect on mortality using a validated turbidimetric assay.

The study included 171 patients on chronic hemodialysis; mean age was 59 years and 54% were men. Kaplan-Meier analysis demonstrated that patients on hemodialysis with a denser clot structure had increased risks for all-cause and cardiovascular mortality (log rank P=.004 and P=.003, respectively).

Following adjustment for age, diabetes, sex, and duration of dialysis or fibrinogen, C-reactive protein, and complement C3, Cox regression models confirmed that denser clots are independently related to risk of mortality.

The researchers also purified fibrinogen from healthy controls and from dialysis patients for additional investigation. Purified fibrinogen from the controls had no post-translational modifications; however, fibrinogen from the dialysis patients was glycosylated and guanidinylated.

“In patients on hemodialysis, a denser clot structure may be a potent independent risk factor for mortality,” according to the researchers.

Prevalence of Atrial Fibrillation in Patients on Chronic Hemodialysis

Risk factors of stroke and thromboembolism in patients on hemodialysis include atrial fibrillation (AF). Oliver Königsbrügge, MD, and colleagues recently conducted a study designed to identify the prevalence of AF in a population-based cohort of patients on hemodialysis.

The researchers also sought to define the practice patterns of antithrombotic therapy for stroke prevention in AF.

The researchers analyzed cross-sectional data of 626 patients enrolled in the Vienna Investigation of Atrial Fibrillation and Thromboembolism in Patients on Hemodialysis, an ongoing prospective observational cohort study. Median age of the patients in the current analysis was 66 years, and 63.4% were men. The researchers conducted a structured interview with each patient, recent and archived electrocardiograms were viewed, and medical histories were verified with electronic records.

Overall, the prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years). Of the 166 patients with AF, 57.8% had paroxysmal AF, 3.0% had persistent AF, 32.5% had permanent AF, and 6.6% had newly diagnosed AF. In multivariable analysis, there were independent associations between AF and age, male sex, history of venous thromboembolism, congestive heart failure, history of or active cancer, and time on hemodialysis. In 84.4% of patients with AF, antithrombotic treatment was used: anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%. Vitamin-K-antagonists were used more commonly than low-molecular-weight heparins (30.1% vs 19.9%).

In conclusion, the researchers said, “The prevalence of AF is high among hemodialysis patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in hemodialysis patients with AF.”


Spain’s High Rate of Deceased Organ Donation
American Journal of Transplantation. doi:10.1111/ajt.14104

Spain has a very high rate of deceased organ donation. In 2015, there were 40 donors and more than 100 transplant procedures per million population. According to Rafael Matesanz, MD, director of the National Transplant Organization in Spain, the success of the Spanish organ donation program “derives from a specific organization approach designed to ensure the systematic identification of opportunities for organ donation and their transition to actual donation.” The program also promotes public support for donation of organs after death.

In light of the decline in the incidence of brain death and changes in end-of-life practices that began in 2000, the Spanish transplant system adopted the 40 donors per million population plan, with three specific objectives: (1) promoting the identification and early referral of possible organ donors from outside the intensive care unit to consider elective non-therapeutic intensive care and incorporate the option of organ donation into end-of-life care; (2) facilitating the use of organs from expanded criteria and non-standard risk donors; and (3) developing the framework for the practice of donation after circulatory death.

This article outlines the actions undertaken and the impact of those actions on donations and transplantations.