Tuesday, October 19, 2021

A promising new way to help patients with kidney disease

Every year, an estimated 785,000 people in the United States are diagnosed with kidney disease, while approximately 40,000 people die from the illness each year. Because the disease is often inherited, the incidence of kidney disease — and deaths from it — is likely to rise in coming years. Even in the absence of genetic clues, to adequately diagnose kidney disease and to help reduce the risk of kidney disease, anyone with symptoms needs to see a medical professional, who will use a simple blood test that checks for five different levels of the protein creatinine. The prevalence of CKD has actually declined in the past several decades, but the true incidence of the disease is much greater, because when appropriate medical treatment is delayed, the progressive scarring of the kidneys can cause irreversible damage to the organs and the risk of kidney failure increases. What if, rather than rushing to schedule this blood test, we could identify those with kidney disease before symptoms develop?

Some researchers believe that if we can identify individuals with hereditary kidney disease at an early stage, we can intervene to prevent further damage from occurring. And this challenge is not an unreasonable one. In 2015, the Partnership for Prevention found that 80 percent of life-saving and preventable conditions are solved with simple lifestyle changes. But given that lack of awareness of a condition also leads to poor outcomes, for the majority of cases, we need data to guide our interventions and interventions.

However, we have barely started to catch up. According to the latest report from the CDC, nearly 40 percent of the U.S. population has undiagnosed kidney disease. Given the prevalence of the disease, the new benefit would not be simply removing the screening from the medical treatment list — there are already more than 10 million Americans living with a previous diagnosis of kidney disease.

Remicade, a life-saving drug, was first approved in the U.S. in 1991 for use in patients with kidney disease. But around 15 years later, data from a retrospective study published in JAMA-Internal Medicine showed that hypertension patients are 70 percent more likely to die from kidney disease if they are taking a blood pressure medication and the following year their patients are diagnosed with kidney disease. Unfortunately, this appears to be at least partly an effect of lower levels of creatinine in blood, without explanation of the cause.

This suggests that even in the absence of inherited genetic causes of kidney disease, patients need to be detected early in their clinical course, whether through the kidney function test or through another screening. A simple blood test used as part of an assessment of overall risk of kidney disease in the population may be an especially effective way to identify people who have a genetic predisposition to kidney disease, and might lead to more timely and effective treatment.

Since its approval, more than 35,000 patients have been approved for the first wave of Ricade, which increases structural protection of the kidney. But in 2016, a new version of Ricade, known as Megra1, was approved to treat patients with chronic kidney disease, even though patients with chronic kidney disease have significantly higher risk of kidney disease, therefore making them significantly more likely to benefit from Ricade. The new version of Ricade, released in January 2018, works by increasing the ability of proteins in the urine to bond with protective factor-11, which triggers production of calcium in kidney tissue. The benefits from the new Ricade regimen have been shown in a New England Journal of Medicine article to have improved quality of life and decrease mortality in patients with CKD.

Just to be clear, early detection of all forms of kidney disease — both hereditary and nonhereditary — is still not a perfect solution, and especially given that the range of conditions is relatively small. But because this gap still exists, we need to develop new approaches in order to more accurately and timely identify those who are at risk and need early intervention.

The type of test we envision focuses on the protein levels in the blood and would allow us to identify the minority of people who have a genetic predisposition to a potentially life-threatening disease. Through new-generation predictive tests such as pre-hemispheric, non-invasive and liquid chromatography techniques, we might be able to take pre-symptomatic genetic tests for chronic kidney disease and place them on the same level as blood tests for anticoagulants. And thanks to improvements in molecular diagnostics, these tests could become as easy as filling out a paper prescription, making it easier for individuals to request a screening test and quicker for us to arrive at a diagnosis.

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