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Clinical Development

Chronic Kidney Disease & Its Impact on Clinical Development – Part 1

  • January 18, 2021
The prevalence of chronic kidney disease (CKD), one of today’s leading public health issues, is on the rise, and with it comes a number of adverse health outcomes, including an increased risk of cardiovascular disease (CVD). Since CKD is a broad diagnosis that can have a variety of underlying causes, a beneficial focus of current research strategies has been to identify biomarkers and develop diagnostics that can help stratify patients into clinically relevant categories and help guide their management.

Recently, medical and operational experts from our nephrology team presented a webinar on this topic. The webinar, which can be viewed in its entirety here, specifically focused on how our deepening understanding of CKD is impacting clinical development. Over the next several weeks, we will build off each topic that was addressed during the presentation. In this post, we will lay the groundwork by defining CKD and discuss its classification system.

What is Chronic Kidney Disease?

CKD is the result of alterations in kidney structure and/or function, with the severity dependent on a number of factors, including its underlying cause, which varies from patient to patient. Imaging techniques such as ultrasound and computerized tomography (CT) are used to visualize structural changes or abnormalities resulting from kidney damage or congenital causes, while urinalysis can be used to detect blood or protein in the urine — another indication of kidney damage.

These techniques allow nephrologists to identify CKD and in conjunction with the level of glomerular filtration rate (GFR), assist with staging of the renal dysfunction without necessarily knowing the underlying cause. However, in order to be diagnosed with CKD, these abnormalities will have had to have persisted for a minimum of three months in order to rule out reversible, or acute causes of kidney injury.

The ability for ease of diagnosis and staging of CKD in this way subsequently increased disease awareness and changed the paradigm for the management of CKD.

The Five Stages of CKD

In the webinar, Dr. Ajay Srivastava, one of our Senior Medical Directors, states “that the development of a staging, or classification, system for CKD was absolutely profound as it changed the very notion that kidney disease was an uncommon, grave disease process that was cared for only by subspecialists — including nephrologists — to one that was actually rather a more common condition with a range of severity that could actually be identified and managed earlier by other clinicians.”

Prior to the development of the CKD classification system which, in turn, offered this increased level of awareness, it would not be uncommon for patients to be seen for the first time by a nephrologist, only to find out that they may require immediate dialysis. Thankfully, with earlier identification and classification comes opportunity for early intervention that make it possible to slow the progression of CKD.

In addition to guiding clinicians in their treatment decisions, GFR — a measure of the total filtration rate of all nephrons in the kidney — provides an indirect measure of functional renal mass. GFR also forms a basis of eligibility requirements for clinical trials. This is true for trials ranging from early- to late-stage studies, as well as trials involving healthy volunteers, to those recruiting patients with end-stage renal disease (ESRD) or kidney failure. Unfortunately, many trials do not include patients with advanced CKD. In fact, up to 75 percent of clinical trials may exclude patients with CKD, which are really the population that needs the therapy.

The five stages of CKD are based on GFR measurements and range from G1 (normal or least severe) to G5 (most severe/kidney failure). Substages help to further classify patients and direct treatment options. Patients who have a GFR at, or above, 60 mL/min/1.73m2 are not considered to have CKD unless they have other markers of kidney disease, such as abnormal urine sediment and/or anatomical abnormalities. On the other end of the scale, patients with a GFR of less than 15 are considered to be in kidney failure and renal replacement therapy (also known as dialysis) or kidney transplantation may then be required.

In addition, increasing proteinuria — and more specifically, albuminuria — worsens outcomes for patients with CKD. As CKD progresses, so does risk associated with all-cause mortality, cardiovascular morbidity and mortality, CKD progression, AKI and ESRD development, and these are further amplified with proteinuria.

Now that we’ve laid the framework of CKD, our next blog post will take a look at biomarkers for chronic kidney disease and outcome considerations for clinical trials.

You can watch the webinar in its entirety here: Chronic Kidney Disease: How A Deeper Understanding of the Disease Is Impacting Clinical Development