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The Underrecognized Epidemic of Chronic Kidney Disease

The Chronic Renal Insufficiency Cohort (CRIC) began in 2003 

A sense of urgency: That’s the feeling I got when talking to researchers for a story on chronic kidney disease (CKD) in the latest issue of Penn Medicine magazine out soon. That story dives deep into the process of how, for nearly two decades, teams from Penn and other institutions have been investigating the disease under the largest epidemiological study of kidney disease in the United States, known as Chronic Renal Insufficiency Cohort (CRIC), to better understand and treat it. But, in reporting that story, what also stood out was that for just as long these researchers and many others in the nephrology community have been sounding an alarm. The disease, they say, is a growing public health issue deserving of more attention and resources.

Today, CKD – a disease where the kidneys progressively fail over time – affects nearly 33 million Americans and is expected to grow to 36 million over the next 10 years. The prevalence of end-stage renal disease, the last and most deadly stage of CKD, continues to rise by about 21,000 cases every year, as well. The cost is equally surprising. Medicare spending has reached about $80 billion annually treating people with CKD, with a good part of that going toward dialysis treatments, according to a 2016 study in the American Journal of Public Health. Statistics from the World Health Organization and other international bodies show it’s a mounting global crisis, too.

Yet, awareness and research funding continue to lag behind those of other diseases.

“We have been laboring to have the health care community, let alone the American public, understand that one person in seven people has kidney disease, and they don’t know it by and large,” said Raymond Townsend, MD, the lead clinical CRIC investigator at Penn, and a professor of Medicine in the division of Renal-Electrolyte and Hypertension. “Consequently, people just don’t think about it.”

Much of this stems from it being a “silent killer.” Ninety percent of people with CKD aren’t aware they have it because symptoms, like constant fatigue and vomiting, typically don’t appear until the later stages. That’s when the kidneys are near failure and either dialysis or a transplant is necessary. But the problem likely started years – and sometimes decades – before.

For their part, government agencies and organizations like the National Kidney Foundation and the International Federation of Kidney Foundations run public awareness campaigns to educate patients about CKD, encouraging them and health care providers to be more proactive about checking the kidneys. This is particularly important for patients who suffer from diabetes and hypertension, two major risk factors for CKD. The theme for this year’s World Kidney Day in March was “Kidney Health for Everyone Everywhere” and emphasized the need for early prevention and detection.

A routine urine test, often performed in an annual checkup, can reveal how well the kidneys are functioning. It screens for too much protein, an indication that they’re not filtering out waste properly. The test delivers a score called an estimated glomerular filtration rate (eGFR), which also considers gender, race, and age.

But screening for the disease and acting upon it remain a challenge in clinics in the United States. Not every hit is flagged, and patients aren’t always referred to a specialist. There are also guidelines today to screen and diagnose CKD, but they’re often not followed, experts say. A lack of available interventions to slow or treat the progression of the CKD directly may be to blame for inaction.

“The nephrology community has been trying to focus on lab reporting, to ensure the generalists, the internists, the pediatricians, the OB/GYN physicians—the doctors who order kidney function tests the most—are tuned into detecting CKD and referring people to appropriate professionals,” said Harold I. Feldman, MD, MSCE, chair of Biostatistics, Epidemiology and Informatics in the Perelman School of Medicine, and principal investigator and national study chair for CRIC.

“The notion that there are no effective treatments, is overstated,” he added. While it may be true that physicians don’t have tools to fully arrest the progression of CKD, they can more effectively use drugs to treat the diseases associated with CKD, like diabetes, hypertension, and cardiovascular issues.

“I can do things that are not directly addressing kidney disease progression, to potentially very good effect,” he said. “I can aggressively treat patients’ blood pressure, their diabetes, or address the abnormalities of their lipid profile.”

The other challenge is research funding, a critical part of helping to reduce the burden of disease. Because there’s still so much researchers don’t know about CKD, a heterogenous disease that can affect patients differently, more studies are necessary to understand its progression and how to slow or stop it.

That’s what the CRIC study has been after since 2001. Researchers have been following over 5,500 patients to learn more about what’s driving that progression, its co-morbidities—particularly heart diseases—and how it impacts the body in other ways. Diabetes and hypertension are major players, but there are others, like genetic or possibly epigenetic factors, that appear to be involved. Many questions remain around all of these. And finding answers takes increased support.

While CRIC has received nearly $8 million every year from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) since it began in 2003, overall, kidney disease research funding pales in comparison to funding for other diseases.

“If you look at a graphic of the number of dollars funded by the NIH, for example, in clinical trials, and look at where kidney disease falls, it’s low,” Townsend said. “We spend more money on studies that look at Alzheimer’s disease, HIV/AIDS, and cancer far more than we spend on kidneys.”

According to the aforementioned study in the Journal of American Public Health, the federal government spends $568 on cancer research per patient compared to $29 on kidney research per patient, despite kidney disease taking more lives every year than prostate and breast cancer. Funding for heart disease and HIV/AIDS rank higher, too.

The authors argue that increased funding for kidney disease research could lead to scientific advances similar to what other well-funded areas of research have experienced, from both federal and private dollars.

Still, even with smaller research investments and fewer clinical trials, a number of promising discoveries have emerged over the years out of studies, including CRIC, which has provided new insights into genetic markers and cardiovascular events.

That work continues, thanks to an award last year from the NIDDK extending CRIC for another five years. In its latest phase, researchers will turn to artificial intelligence and persistent monitoring for the first time to study CKD. They’ll now be able to track patients’ physical activity and collect blood samples more frequently because of at-home finger pricks. Using this new data, as well as historical data, the team will employ sophisticated bioinformatics approaches to spot unseen traits and patterns of CKD that traditional approaches may have missed.

“It’s still underappreciated as a public health issue,” Feldman said, “but we have a made a lot of inroads.”

To read more about Penn’s efforts to better understand this elusive disease and the newest phase of research, check out the spring/summer issue of Penn Medicine magazine.

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