High-impact clinical trial results may affect kidney medical care

The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented online at ASN Kidney Week 2021 from November 4-7.

  • Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by overproduction of oxalate by the liver, leading to progressive kidney disease. In the phase 3 ILLUMINATE-C study, patients with PH1 and chronic kidney disease (including patients on hemodialysis) who were treated with lumasiran ((an RNAi-based medicine indicated for the treatment of of PH1 to lower urinary oxalate levels in pediatric and adult patients) have shown substantial reductions in plasma oxalate. “We know that elevated plasma oxalate levels are associated with serious and life-threatening complications, including oxalate deposition in the heart, bones, skin and eyes of these patients – a condition known as systemic oxalosis – resulting in dysfunction of multiple organs, “said lead author Mini Michael, MD, pediatric nephrologist, Baylor College of Medicine / Texas Children’s Hospital. “Thus, a decline in oxalate levels of the magnitude seen in this study is promising and we hope it will result in Long-term improved clinical outcomes, including oxalosis, which we plan to further evaluate during the extension period of ILLUMINATE-C. ” ILLUMINATE-C, a phase 3 single-arm study of lumasiran in patients with primary hyperoxaluria type 1 and stages 3b-5 CRF, including those on hemodialysis
  • IgA nephropathy is a common cause of kidney failure, especially in young people, but no specific treatment has been shown to date to prevent significant kidney results. The Therapeutic Evaluation of STeroids in IgA Nephroopathy Global (TESTING) study evaluated the effects of oral methylprednisolone compared to placebo on key renal outcomes and safety in patients with IgA nephropathy. A total of 503 participants were randomized to receive methylprednisolone (257) or placebo (246), including 262 at a full dose (0.6-0.8 mg / kg / day, maximum 48 mg / day, for 2 months then weaning of 8 mg / day / month) or placebo and 241 at a reduced dose (0.4 mg / kg / day, maximum 32 mg / day, weaning of 4 mg / day / month) or placebo. Over a mean follow-up of 4.2 years, methylprednisolone reduced the risk of the primary endpoint (consisting of 40% drop in eGFR or renal failure) by 47% and renal failure by 41%. The risk reduction was seen with both doses. Serious adverse events were more frequent with methylprednisolone compared to placebo (28 versus 7 patients), especially with the full dose (22 versus 4) versus the reduced dose (6 versus 3). “The TESTING trial showed that two different doses of an inexpensive type of oral steroid taken for 6 to 9 months reduced the risk of major renal events and kidney failure. The risk of adverse events, especially d ‘infections, was increased primarily with high dose therapy, suggesting that reduced dose therapy best balances risks and benefits, “said co-lead author Vlado Perkovic, MBBS, PhD, University of New York. – South Wales, Australia. The TESTING Study: Steroids vs. Placebo in High-Risk IgA Nephropathy
  • In EMPEROR-Preserved, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, reduced cardiovascular deaths and hospitalizations for heart failure and slowed the decline of renal function in patients with heart failure and heart failure. ‘a preserved ejection fraction (HFpEF), with or without diabetes. A new analysis of the trial data showed that these benefits were felt in patients regardless of the presence or absence of chronic kidney disease and across a wide range of baseline kidney functions. The analysis included 5,988 randomized patients, of whom 3,198 (53%) had prevalent chronic kidney disease. “In the active and so far disappointing search for a therapy to help patients with ICFpEF, the EMPEROR-Preserved trial is the first trial showing unequivocal cardiac and renal benefits in such patients. This trial reproduces the same benefits also observed in patients. with heart failure and reduced ejection fraction, ”said lead author Faiez Zannad, MD, PhD, University of Lorraine, Inserm INI-CRCT, France. “Therefore, empagliflozin is the first drug to show consistent improvement in cardiovascular outcomes and a slowing of decline in kidney function across the spectrum of kidney function, including patients with chronic kidney disease, across the board. the spectrum of cardiac ejection fraction and in patients with and without diabetes. ” Empagliflozin and results in heart failure with preserved ejection fraction and CKD
  • Nephrotic syndrome is one of the most common kidney diseases in children. Previous studies suggest that 8 to 12 weeks of prednisone is an effective and safe initial treatment. There is preliminary evidence that young children (Randomized controlled trial comparing initial 3-month versus 6-month prednisone treatment in young children (
  • In patients with chronic kidney disease (CRF), anemia is often underdiagnosed and undertreated, although it is a significant complication of CRF. The ASCEND program, which includes more than 8,000 patients with CRF, includes two pivotal phase 3 studies examining the cardiovascular efficacy and safety of daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, as a new alternative to injectable erythropoiesis stimulating agents (ESAs), the current standard of care. These studies independently met their primary endpoints of safety and efficacy, showing that daprodustat improved or maintained hemoglobin without increased cardiovascular risk compared to ESAs in both dialysis and non-dialysis patients. “Evidence has shown that daprodustat is as effective and safe an oral option as ESA and that it is well tolerated, indicating that the use of an oral agent, such as daprodustat, may help improve accessibility and adherence for patients with CKD anemia who cannot normally access treatment because in many patients ESA must be administered by a health care provider, ‘said the senior author and chair of the ASCEND program steering committee Ajay Singh, MBBS, FRCP (UK), MBA, nephrologist at Brigham and Women’s Hospital and Harvard Medical School. “In addition to stimulating the natural production of erythropoietin, the daprodustat causes changes in markers of iron metabolism in the body, which may be beneficial, and it works well in patients who have a poor response to ESA. ” ASCEND program: Efficacy and safety of ASCEND-D and -ND and overall conclusion of MACE
  • Chlorthalidone was approved by the United States Food and Drug Administration for the treatment of hypertension in 1960, but it is currently only prescribed for people without advanced kidney disease. In the Chlorthalidone Chlorthalidone in Chronic Kidney Disease CLICK study, 160 patients with hypertension and stage 4 chronic kidney disease were randomized to either placebo or chlorthalidone. This low-cost drug lowered patients’ blood pressure within 4 weeks, and this drop was sustained over a 12-week treatment period. The adjusted change from baseline in 24-hour systolic blood pressure was -0.5 mm Hg in the placebo group and -11.0 mm Hg in the chlorthalidone group. Additionally, the drug reduced albuminuria (a marker of kidney dysfunction) by 50% over 12 weeks, suggesting that it may have protective effects on the kidneys. “In addition to the side effects that we commonly see with the use of this medicine in people without kidney disease, we have seen an increased risk of reversible changes in kidney function, especially when people were also given medicines called diuretics. ‘cove, “said senior author Rajiv Agarwal, MD, of Indiana University School of Medicine and Roudebush VA, Indianapolis. “Thus, careful monitoring is required while using this drug.” Chlorthalidone for hypertension in advanced CRF (CLICK): a randomized, double-blind trial
  • The Ellipsys Pivotal Trial demonstrated the early safety and efficacy of a minimally invasive procedure to create an arteriovenous fistula in the arms of patients requiring hemodialysis. In a recent analysis of long-term data, investigators found that this procedure provided sustainable access for hemodialysis for 5 years with a high rate of fistula use and low rates of secondary procedures and complications. “The data demonstrate the safety, efficacy and durability of Ellipsys fistula as an alternative to surgery for patients requiring dialysis,” said senior author Jeffrey Hull, MD, of the Richmond Vascular Center. “In ongoing studies, the clinical costs and benefits of Ellipsys fistula are being evaluated.” Long-term results of Ellipsys percutaneous fistula for hemodialysis
  • In the phase 3 ADVOCATE trial, patients with vasculitis associated with anti-neutrophil cytoplasm autoantibodies (ANCA) (a group of autoimmune diseases characterized by inflammation and damage to small blood vessels) were randomized to receive avacopan, an oral inhibitor of the complement C5a receptor. , or a decrease in prednisone against a background of cyclophosphamide (followed by azathioprine) or rituximab. Patients in the avacopan group experienced better recovery of renal function compared to patients in the prednisone group, especially patients with advanced renal impairment. Effect of Avacopan, a selective C5a receptor inhibitor, on renal function in patients with ANCA-associated vasculitis

ASN Kidney Week 2021, the largest nephrology meeting of its kind, will provide a forum for nephrologists and other kidney health professionals to discuss the latest research findings and participate in educational sessions related to advances in the care of patients with kidney disease and related disorders. .

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American Society of Nephrology


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