High-Impact Clinical Trials Yield Results that Could Improve Kidney Care


Newswise — Washington, DC (November 8, 2019) — The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented at ASN Kidney Week 2019 November 5–November 10 at the Walter E. Washington Convention Center in Washington, DC.

  • Many transplant recipients receive the immunosuppressive drug mycophenolate mofetil despite poor evidence that it is better than an older and far less expensive alternative, azathioprine. In the ATHENA trial, results confirmed previous evidence that azathioprine is as effective as mycophenolate mofetil in preventing chronic kidney rejection, and it has a similar safety profile. “Due to higher costs of brand name mycophenolate and concerns on generic formulation quality, no evidence supports its further use over azathioprine,” said Paolo Cravedi, MD, PhD, lead author of the study.

Mycophenolate Mofetil vs. Azathioprine in Kidney Transplant Recipients on Steroid-Free, Low-Dose Cyclosporine Immunosuppression: The ATHENA Trial

  • Hyperreactive B cells of the immune system seem to play a role in lupus, an autoimmune disease that often leads to kidney damage, and treatment with rituximab, an antibody directed against the CD20 protein on B cells, depletes B cells to a certain extent. In the NOBILITY trial, a different antibody against CD20, called obinutuzumab, improved the kidney health of patients with lupus nephritis compared with placebo. “In this study, treatment with obinutuzumab, in combination with standard of care (mycophenolate and corticosteroids), demonstrated enhanced efficacy compared with placebo plus standard of care in achieving a kidney response at one year, with increasing responses seen at 18 months,” said lead author Brad Rovin, MD, of The Ohio State University. “No new safety signals were observed with obinutuzumab. We await two-year data from this study and are preparing to initiate a global phase 3 study in the first half of next year.”

A Phase 2 Randomized, Controlled Study of Obinutuzumab with Mycophenolate and Corticosteroids in Proliferative Lupus Nephritis

  • Patients with chronic kidney disease (CKD) undergoing hemodialysis commonly experience a systemic itch—or pruritus— that negatively affects their quality of life and health outcomes. Difelikefalin is a novel, peripherally restricted, kappa opioid receptor (KOR)–selective agonist, which exerts anti-pruritic effects via activation of KORs located on peripheral sensory neurons and immune cells. The phase 3 KALM-1 trial was conducted to evaluate the reduction of itch intensity and improvement in itch-related quality of life in difelikefalin-treated patients with CKD undergoing hemodialysis vs. placebo. Patients were randomized to receive an IV bolus of 0.5 mcg/kg difelikefalin (N=189) or placebo (N=188) 3 times a week (after each dialysis session) over 12 weeks. “There is a substantial unmet need for effective treatments for moderate-to-severe pruritus in hemodialysis patients. In this trial, difelikefalin led to clinically meaningful reductions in itch intensity and improved itch-related quality of life in a CKD patient population undergoing hemodialysis, with no major safety concerns,” stated lead author Steven Fishbane, MD.

Efficacy and safety of difelikefalin in patients undergoing hemodialysis with pruritus: Results from a phase 3, randomized, controlled study (KALM-1) 

  • Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases and is rising in prevalence. The presence of kidney disease in patients with HFpEF often results in worse outcomes for patients, with limited current treatment options. Investigators assessed the long-term kidney effects of sacubitril/valsartan, which combines the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, in 4,822 patients with HFpEF enrolled in the PARAGON-HF trial. This combination simultaneously relieves congestion and lowers blood pressure. “In an analysis of the PARAGON-HF trial, we found that sacubitril/valsartan (compared with valsartan) resulted in a lower risk of the prespecified kidney outcome, and that patients with lower kidney function may have benefited to a greater extent from fewer cardiovascular events,” said lead author Finnian Mc Causland, MBBCh. “Future studies are required to investigate the reasons for these benefits and to determine which patients will benefit most.”

Effect of Angiotensin-Neprilysin Inhibition on Renal Outcomes in Heart Failure with Preserved Ejection Fraction

  • Vitamin D and omega-3 fatty acid (often sold as fish oil) supplements do not help people with type 2 diabetes stave off chronic kidney disease, according to a five-year study of kidney function in 1,312 adults with type 2 diabetes. In the trial, participants were randomly assigned to vitamin D3 (2000 IU daily) or placebo and to omega-3 fatty acids (eicospentaenoic acid and docosahexaenoic acid, 1 g daily) or placebo. “We wanted this study to clarify whether these supplements have any real kidney benefit in adults with diabetes. Even if it’s not the result we hoped for, closing a chapter is useful for patients and clinicians and researchers alike,” said lead author Ian de Boer, MD, of the University of Washington School of Medicine.

Effect of vitamin D and omega-3 fatty acid supplementation on kidney function in patients with type 2 diabetes:  a randomized clinical trial

  • Animal models, epidemiological studies, and small clinical trials have suggested the possibility that reducing blood levels of uric acid might prevent or slow the progression of kidney disease associated with diabetes. The Preventing Early Renal Loss in Diabetes (PERL) study, which was funded by NIDDK and JDRF, has now provided an unequivocal answer to this question in patients with type 1 diabetes and mild-to-moderate diabetic kidney disease. In this large, randomized, placebo controlled, international, multicenter clinical trial, 3 years of sustained reductions of blood levels of uric acid with the generic drug allopurinol did not benefit patients’ kidney health. “Thus, the field should look elsewhere for novel ways to benefit this debilitating diabetic complication in patients with similar characteristics to the PERL participants,” said lead author Alessandro Doria, MD, PhD, MPH. “The PERL network and study infrastructure can be leveraged for this purpose.”

Preventing Early Renal Loss in Diabetes (PERL) Study: Outcome of a 3-Year Trial of Serum Uric Acid Reduction with Allopurinol

  • A substantial proportion of patients with heart failure have or develop kidney disease. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which lower blood sugar, have been shown to delay the progression of kidney disease and reduce the incidence of cardiac events in patients with type 2 diabetes and kidney disease. Researchers recently compared the SGLT-2 inhibitor dapaglifozin with placebo in patients with heart failure and reduced ejection fraction in the Dapagliflozin in Heart Failure with Reduced Ejection Fraction Trial (DAPA-HF). The team found that overall, dapaglifozin reduced morbidity and mortality substantially. This benefit was apparent regardless of whether patients had kidney disease. Dapaglifozin was also safe in patients with chronic kidney disease, with no increased incidence of hypotension or other serious adverse events. “These data suggest that the dapaglifozin is an effective and safe addition to our armamentarium in patients with heart failure and reduced ejection fraction and concomitant chronic kidney disease,” said lead author Scott Solomon, MD.

The Dapagliflozin in Heart Failure with Reduced Ejection Fraction Trial (DAPA-HF): Outcomes in Patients with CKD and Effects on Renal Function

ASN Kidney Week 2019, the largest nephrology meeting of its kind, will provide a forum for more than 13,000 professionals to discuss the latest findings in kidney health research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Kidney Week 2019 will take place November 5 – November 10 in Washington, DC. 

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 20,000 members representing 131 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.

 

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