SGLT-2 for Stage 3 CKD; Opioids for CKD; Kidney Transplant Discard & Disabilities

SAN DIEGO -- Novel therapies combining multidisciplinary kidney care were at the forefront of the American Society of Nephrology's Kidney Week 2018.

Some of the new research presented included use of high doses of iron as an alternative to erythropoiesis-stimulating agents for hemodialysis-related anemia, a phase II trial assessing an investigational dual AT₁/ET_A receptor blocker for focal segmental glomerulosclerosis treatment, and kidney outcomes with intensive diabetes and blood pressure control. Below are just a few more of the research highlights presented at this year's meeting.

Bexagliflozin Clinical Trial

The novel SGLT-2 inhibitor bexagliflozin effectively lowered HbA1c levels in people with advanced chronic kidney disease (CKD), according to a phase III clinical trial. The analysis included 300 individuals with type 2 diabetes, including those with stages 3a and 3b CKD. After 24 weeks of treatment, all individuals on treatment had an average A1c reduction by 0.37% compared with placebo (95% CI 0.20-0.54, P<0.0001).

Patients with stage 3a CKD had an average drop of 0.31%, while stage 3b CKD individuals had a drop in A1c of 0.43%. Treatment with the investigational SGLT-2 inhibitor was also associated with significant reductions in body weight, systolic blood pressure, fasting plasma glucose, and albuminuria -- consistent with other agents in this class.

"Roughly one third of diabetics suffer from stage 3 CKD. This study suggests that bexagliflozin could be of benefit to this group," said the study's lead author, Andrew Allegretti, MD, of Massachusetts General Hospital in Boston, in a statement.

Opioid Use in CKD

In an analysis of prescription opioid trends in the U.S. between 1999 and 2014, Daniel Murphy, MD, and Robert Foley, MD, both of the University of Minnesota, and colleagues found that use was much more prevalent in people with CKD. Specifically, the team found that on average 5.4% of people without CKD were prescribed opioids compared with 7.5% of those with CKD (P<0.001). Some of the clinical factors of CKD tied to a higher likelihood of use included a lower estimated glomerular filtration rate and albuminuria. Among patients with CKD prescribed opioids, 28% of this use was attributed to the patient's kidney disease.

"We were not surprised to see greater opioid use in those with chronic kidney disease compared to those without chronic kidney disease. We were surprised to see such large proportions using these medications in certain subgroups within chronic kidney disease," Murphy and Foley jointly explained to MedPage Today. "We recommend cautious, evidence- and guideline-based prescribing of opioid medications for those with chronic kidney disease."

U.S. Discard Rates: How Do We Compare?

In a head-to-head analysis comparing discard rates for donated kidneys in the U.S. and France, Olivier Aubert, MD, PhD, of the Paris Translational Research Center for Organ Transplantation, and colleagues found that the U.S. was much more conservative in its use of donated kidneys. Between 2004 to 2014, France saw a rise in the Kidney Donor Profile Index -- from 54 to 67 -- while the U.S. had only a small rise, from 42 to 44. This equated to France exhibiting much more aggressive use of donor kidneys, Aubert told MedPage Today.

"The fact that in the U.S. more kidneys are discarded compared to France was known, but it was surprising to observe the very impressive difference in the mean transplanted donor's age between the two countries (36.51 ± 17.02 years in the U.S. versus 50.91 ± 17.34 in France). If U.S. centers adopted greater willingness to accept kidneys from older donors and other higher-risk donor groups, this change would provide an additional 132,445 allograft-life years to U.S. transplant candidates over 10 years," he said.

"In the U.S. alone, approximately 95,000 individuals are waiting for a kidney transplant. New, creative solutions to address this concern are needed. The French transplant system offers a useful contrast, because French transplant programs face less regulatory scrutiny than U.S. programs and do not use donor kidney biopsies in organ acceptance decisions," he added.

Disabilities in Kidney Transplant Recipients

A prospective study of 500 patients who received a kidney transplant found that nearly a quarter reported some form of physical disability. Alvin Thomas, a PhD candidate at the University of North Carolina at Chapel Hill, and colleagues found that certain forms of disability in a recipient were tied to worse outcomes. Specifically, having a visual disability (adjusted HR 3.98, 95% CI 1.38-11.50, P=0.01), as well as a hearing disability (aHR 3.49, 95% CI 0.95-12.85, P=0.06) were tied to a higher risk of graft failure. Furthermore, a walking disability was linked to a significantly higher risk of mortality after transplantation (aHR 4.12, 95% CI 1.66-10.24, P=0.002).

"We were glad to see that the majority of those with physical impairments or disabilities did not experience any difference in post-transplant outcomes compared to those without physical impairments or disabilities," Thomas told MedPage Today.

"Our work was not able to identify the mechanisms by which individuals with visual impairments were at higher risk of graft failure and those with walking disabilities were at higher risk of mortality. So, future work will be necessary to identify barriers and solutions so that all kidney transplant recipients can enjoy better outcomes regardless of their disability status," he explained, adding that in the meantime, transplant hospitals may consider providing additional supportive care for transplant recipients with disabilities or impairments both pre- and post-transplant.

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