Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.

Significance Statement: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope).

Validity and Utility of a Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression: A Review.

Clinical trials in nephrology often use composite end points comprising clinical events, such as onset of ESKD and initiation of kidney function replacement therapy, along with a sustained large ( e.g. , ≥50%) decrease in GFR.

Perioperative THR-184 and AKI after Cardiac Surgery.

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI.

The establishment and validation of novel therapeutic targets to retard progression of chronic kidney disease.

The focus of this article is to define goals and resulting action plans that can be collectively embraced by interested stakeholders to facilitate new therapeutic approaches to mitigate chronic kidney disease progression. The specific goals include identifying druggable targets, increasing the capacity for preclinical and early clinical development, broadening the availability of new therapeutic approaches, and increasing investment in the development of new therapies to limit chronic kidney disease. Key deliverables include the establishment of new regional, national, and global consortia; development of clinical trial networks; and creation of programs to support the temporary mutual movement of scientists between academia and the biotechnology and pharmaceutical sector.

Genetic and environmental risk factors for chronic kidney disease.

In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved.