April 2017: Abstract Roundup

Acute Kidney Injury

Algorithm Assists RRT Initiation Timing Decision Making
Clinical Journal of the American Society of Nephrology. 2017;12(2):228-236

Severe acute kidney injury (AKI) that requires renal replacement therapy is associated with a >40% in-hospital mortality rate. There are no standardized recommendations related to clinical decision making regarding initiation of renal replacement therapy for patients with AKI in the medical intensive care unit (ICU).

Mallika L. Mendu, MD, and colleagues conducted a 13-month prospective cohort study from November 2013 to December 2014 in a medical ICU involving implementation of an AKI Standardized Clinical Assessment and Management Plan. The plan is an algorithm designed to aid decision making for clinicians treating patients with AKI.

Patients whose clinicians adhered to the plan’s recommendation to start RRT had lower in-hospital mortality and 60-day mortality compared with patients whose clinicians did not adhere to the plan’s recommendations (42% vs 63% and 46% vs 68%, respectively; both P<.01). The findings were confirmed following multivariable adjustment for age, albumin, and severity of disease.

In conclusion, the researchers said, “Physician adherence to an algorithm providing recommendations on RRT initiation was associated with lower in-hospital mortality.”

Impact of E-Alerts for Detection of AKI
Nephrology Dialysis Transplantation. 2017;32(2):265-272

Researchers led by Phillippe Lachance, MD, recently conducted a systematic review designed to examine the impact of electronic alerts (e-alerts) for acute kidney injury (AKI) in hospitalized patients. The review focused on randomized, quasi-randomized, observational, and before-and-after studies that included hospitalized patients, e-alerts for AKI, and descriptions of the impact of the e-alerts on one of various care processes, patient-centered outcomes, or resource utilization measures.

In pooled analysis of the six studies included in the review, there was no improvement in risk of mortality or reduction in use of renal replacement therapy with use of e-alerts (odds ratio, 1.05, 95% confidence interval [CI], 0.84-1.31 and 1.20, 95% CI, 0.91-1.57, respectively).

Isolated studies reported improvement in selected care processes.

The researchers said, “In the available studies, e-alerts for AKI do not improve survival or reduce renal replacement therapy utilization. The impact of e-alerts on processes of care was variable. Additional research is needed to understand those aspects of e-alerts that are most likely to improve processes and outcomes.”

Cardiovascular Outcomes Changes in GFR after Initiation of Renin-Angiotensin System Blockade
Kidney International. 2017;91(3):683-690

Acute decreases in glomerular filtration rate (GFR) may be associated with initiation of blockage of the renin-angiotensin system. However, according to Catherine M. Clase, MB, MSc, and colleagues, the prognostic significance of this is unknown. The researchers conducted a post hoc analysis of patients with, or at risk for, vascular disease in two randomized controlled trials.

In 9340 patients new to renin-angiotensin blockade, there was a fall in GFR of ≥15% at 2 weeks after initiating renin-angiotensin blockade in 16% of the patients (n=1480), with persistence at 8 weeks in 7% (n=700). Acute increases and decreases in GFR after initiation of renin-angiotensin blockade were associated with tendencies to increased risk of cardiovascular outcomes; which occurred in 1280 patients, and microalbuminuria, which occurred in 864 patients. The tendencies were primarily statistically nonsignificant.

The researchers said, “Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy.”

Chronic Kidney Disease Emergency Department Use among Patients with CKD
Clinical Journal of the American Society of Nephrology. 2017;12(2):304-314

Patients with chronic kidney disease (CKD) have high healthcare resource use, but there are few data on visits to emergency departments (ED) among this patient population and on the proportion of encounters specifically related to CKD care. Paul E. Ronksley, MD, and colleagues recently conducted a study in Canada to calculate adjusted rates of overall ED use as well as rates of potentially preventable ED encounters.

Following adjustment, rates of overall ED use were highest among patients with more advanced CKD; 5.8% of all ED visits were related to CKD-specific, ambulatory care-sensitive conditions. Approximately 33% of those CKD-related visits resulted in hospital admission. For patients with CKD categories G3A, G3B, and G4, heart failure accounted for >80% of all potentially preventable ED events. For patients on dialysis, hyperkalemia accounted for 48% of all ED visits related to CKD-specific ambulatory care-sensitive conditions.

“Emergency department use is high among patients with CKD, although only a small proportion of these encounters is for potentially preventable CKD-related care. Strategies to reduce emergency department use among patients with CKD will, therefore, need to target conditions other than CKD-specific ambulatory care-sensitive conditions,” the researchers said.

Early Low-Dose ESAs and CKD Progression
Nephrology Dialysis Transplantation. 2017;32(2):279-287

There are few data on whether early intervention with low-dose erythropoiesis-stimulating agents (ESAs) in patients without anemia can delay progression of chronic kidney disease (CKD). Danilo Fliser, MD, and colleagues recently conducted a single-blind, 24-month trial among adults with estimated glomerular filtration rate (eGFR) 30 to 59 mL/min/1.73 m2 and type 2 diabetes mellitus or previous kidney transplantation. Trial participants were randomized to receive low-dose continuous erythropoiesis receptor activator (CERA; n=115) or placebo (n=120). The study’s primary end point was annual change in eGFR.

At baseline, mean eGFR was 40.7 mL/min/1.73 m2 in the CERA group and 39.8 mL/min/1.73 m2 in the placebo group. At the final visit, the mean eGFRs were 39.0 mL/min/1.73 m2 and 39.7 mL/min/1.73 m2, respectively. Median annual reduction in eGFR was 0.5 mL/min/1.73 m2 with CERA versus 0.4 mL/min/1.73 m2 with placebo. There were no significant differences in annual change in eGFR between groups in the subpopulations with type 2 diabetes or kidney transplant.

In conclusion, the researchers said, “Patients with moderate CKD and type 2 diabetes or previous kidney transplantation showed stable renal function that was unaffected by administration of low-dose ESA. In addition, there was no clinically meaningful effect of 2-year low-dose ESA treatment on albuminuria, an important surrogate marker of kidney injury.”

Dialysis

Phosphate-Containing Drugs Contribute to Low Adherence in Dietary Phosphate Limit
Journal of Renal Nutrition. doi:10.1053/j.jrn.2016.09.007

Hyperphosphatemia, associated with all-cause mortality in patients on hemodialysis, is managed by restricting intake of dietary phosphate. However, adherence rates are poor among many patients, particularly among those prescribed medications containing phosphate salts.

Seana M. L. Nelson, MSc, MD, and colleagues conducted a cross-sectional study to quantify the burden of phosphate from prescription medication in patients on hemodialysis.

The researchers reviewed 1744 drug formulations of 124 different medications; of those, 185 contained a phosphate salt. Central nervous system (CNS) medications accounted for 65% of the phosphate-containing medications, followed by cardiovascular (CVD) medications, accounting for 24%. Thirty percent of the study participants were taking at least one phosphate-containing medication; median phosphate burden from prescription medications was 111 mg per day.

In conclusion, the researchers said, “Knowledge about the phosphate content of commonly prescribed drugs within different classes should influence prescribing patterns. Particular consideration of which formulation of CVD and CNS drugs contain phosphate should be applied when prescribing. Phosphate-containing medications can meaningfully contribute to the daily phosphate load in hemodialysis patients; however, this burden will differ based on local dispensing patterns.”

Vitamin K Antagonists Risk Factor for Lower Limb Ulcers
Therapeutic Apheresis and Dialysis. doi: 10.1111/1744-9987.12507

Patients on dialysis may experience peripheral artery disease; vitamin K antagonists promote metastatic calcifications, which are the primary determinants of vascular damage. Andreana De Mauri, MD, and colleagues recently conducted a retrospective study to assess the role of vitamin K antagonists in the development of lower limb ulcers in dialyzed patients.

A total of 316 dialyzed patients were enrolled in the study. Mean age was 68 years, 65% were male, 32% had diabetes, and 43% had ischemic heart disease. Follow-up continued for 36 months.

Sixty patients were on vitamin K antagonist therapy. Those 60 patients were older, had a higher prevalence of heart disease, and were at greater risk for death. The patients in the vitamin K antagonist group developed more ulcers and underwent more lower-limb amputations compared with the other patients in the cohort. Independent risk factors for foot lesions were peripheral artery disease, vitamin K antagonists, and diabetes. Vitamin K antagonists were also an independent risk factor for death.

“Vitamin K antagonists are a potent independent risk factor for the development of the uremic foot syndrome and death,” the researchers said.

Transplantation

HIV-Infected Waitlist Candidates Less Likely to Receive Living Donor Kidney
Clinical Journal of the American Society of Nephrology. doi: 10.2215/CJN.07460716

Jayme E. Locke, MD, and colleagues recently conducted analysis of data from the Scientific Registry of Transplant Recipients linked to Intercontinental Marketing Statistics pharmacy fills (January 1, 2001, to October 1, 2012) to identify and examine kidney transplantation candidates with HIV (HIV+; n=1636) and without HIV (HIV–; n=72,297). HIV+ patients were identified as having filled one or more antiretroviral medications unique to HIV treatment.

Waiting list candidates who were HIV+ were more often young (<50 years of age; 62.7% vs 37.6%); P<.001), more often men (75.2% vs 59.3%; P<.001), more often black (73.6% vs 27.9%; P<.001), had longer dialysis duration (2.5 years vs 0.8 years; P<.001), were more often coinfected with hepatitis C virus (9.0% vs 3.9%; P<.001), and were less likely to remain active on the waiting list (37.7% vs 49.4%; P<.001), compared with those who were HIV–. The likelihood of living donor kidney transplantation was 47% lower among those who were HIV+ (adjusted hazard ratio, 0.53; P<.001).

“Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates,” the researchers said.

L-Carnitine to Protect Against Delayed Graft Function
Journal of Renal Nutrition. doi: 10.1053/j.jrn.2016.11.002

Delayed graft function (DGF) following deceased donor kidney transplantation has significant adverse effects on graft outcomes. A major cause of DGF is ischemia-reperfusion injury during transplantation, which causes a decrease in tissue concentrations of carnitine. Atefeh Jafari, PharmD, and colleagues in Iran recently conducted a pilot study to examine the possible protective effect of L-carnitine against DGF.

The trial included 56 patients undergoing their first kidney transplantation who were randomized to L-carnitine or placebo groups. The intervention group received three divided doses of 3 g of L-carnitine each day for four consecutive days, beginning the day prior to kidney transplantation.

There was no difference in incidence of DGF between the two groups: 18.51% in the L-carnitine group versus 23.8% in the placebo group; P=.68. Within 3 months following kidney transplantation, total allograft failure occurred in six patients in the placebo group and one in the L-carnitine group (P=.05).

The researchers said, “This study showed no protective effects of oral L-carnitine supplementation against DFG occurrence in participants; however, 3-month graft loss was lower in the L-carnitine supplemented group.”

Time-Weighted Variability of Tacrolimus Blood Level and Graft Survival
Nephrology Dialysis Transplantation. 2017;32(2):393-399

There are few data on the effect of variability of tacrolimus blood levels during the early post-transplantation period. Benaya Rozen-Zvi, MD, and colleagues conducted a retrospective cohort study to examine the association between time-weighted variability in the early post-transplantation period and graft survival. The study included all patients undergoing kidney transplantation at the Rabin Medical Center,

Petah Tikva, Israel, between January 1, 2000, and September 29, 2013, who were treated with tacrolimus (n=803).
The researchers defined time-weighted coefficient of variability (TWCV) as time-weighted standard deviation divided by the mean drug level.

The primary outcome of patient and graft survival was calculated with univariate and multivariate Cox proportional hazard model.

There was an association between the high tertile of TWCV of tacrolimus blood levels and reduced graft survival in univariate and multivariate analyses (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.14-2.52; P=.01 and HR, 1.74, 95% CI, 1.14-2.63; P=.01, respectively). There was significant association with the interaction between high TWCV and exposure to inadequately low drug levels and reduced survival (P=.004). There was no significant association between TWCV and high drug blood levels.

“The combination of high TWCV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period,” the researchers said.