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Revolutionizing the diagnosis of chronic kidney disease


The kidneys might be the most overlooked organs in the human body. Their primary function, the removal of waste products, is essential to our survival. Yet everyone knows the importance of maintaining a healthy heart or keeping those brain cells sharp, but has your friend or family member ever asked you if your kidneys were functioning at optimal capacity? Maybe they should. 

According to the National Kidney Foundation, nearly 26 million Americans - one in every nine people – suffer from kidney damage or low kidney function, often slowly progressive, known as chronic kidney disease (CKD). But due to a lack of physical warning signs, CKD had long been a challenge to diagnose. That is, until Chief of the Division of Nephrology Andrew S. Levey, MD proposed that measuring kidney function would be an effective way to define chronic kidney disease and characterize the levels of its severity. This CKD definition and staging system have been important advances that changed clinical practice, research and public health.

“Kidney disease is silent, it doesn’t have symptoms; there are very few biopsies of kidneys and there wasn’t any uniform terminology,” said Levey. “We needed a standardized way to define, identify and estimate the prevalence of CKD and determine its stages, so we could pinpoint the people who suffer from the disease and more effectively help them.”

Levey and his research team have been at the forefront of the development of tests to use in clinical practice for the diagnosis of CKD. Nephrologists use a metric called glomerular filtration rate (GFR) to measure how well the kidneys are functioning. However, direct measurement of GFR requires a five-to-six-hour test that involves an IV line, an injection and hours of waiting. Although it is the most accurate diagnostic test to measure kidney function, it is far from the most practical. 

So in 1999, they announced a new, improved and convenient way to estimate kidney function through a simple blood draw, by estimating GFR from a routinely-measured marker called creatinine, a waste product in the blood. Levey updated and improved the creatinine equation in 2009 and in 2012 showed that the updated equation provides leads to more accurate prognosis of CKD. Today, 300 million creatinine tests are administered in the U.S. every year.

However, creatinine does have some limitations as a marker - since it is produced by muscles, it is less effective at estimating kidney function in people who are very muscular or those who are very sick and have muscle wasting. That population would benefit more from Levey’s 2012 work to expand kidney function markers to include cystatin C. Cystatin C is not affected by muscle and can be used in conjunction with, or in place of, creatinine tests to obtain a more accurate GFR estimate and prognosis of CKD; for the general population, Levey recommends using cystatin C as a confirmatory test for creatinine. Like creatinine, cystatin C can be measured in a simple blood test during an office visit.

“We still have a few years to go before all nephrologists routinely use cystatin C tests, because clinical laboratories are not yet measuring cystatin C using up-to-date assays,” said Levey. “At Tufts Medical Center, we have implemented GFR estimation using cystatin C, and we are proud to be the only place in town where patients can have their GFR measured on site. Unlike other hospitals, our cystatin C assay results are calibrated to the international reference standard, built into our patient information system and reported in our electronic medical record.”

Over the past few years, Levey’s CKD research has been highlighted in several prominent medical journals, including the New England Journal of Medicine, Lancet and the Journal of the American Medical Association.  Last November, Levey was named the 2013 winner of the American Society of Nephrology’s Belding H. Scribner Award, a prestigious honor presented annually to people who have made outstanding contributions to the care of patients with kidney disorders or have substantially changed the clinical practice of nephrology. Jane Friedman of the Gerald J. and Dorothy R. Friedman NY Foundation for Medical Research and the Division of Nephrology recognized Levey for this achievement with a surprise celebration at the Four Seasons, which was attended by many influential nephrologists from across the country, as well as close family and friends.

“I’m very fortunate to work with so many top people in different fields - brilliant physicians, chemists, statisticians, epidemiologists and public health officials - to do state-of-the-art work to tackle the problem of chronic kidney disease,” said Levey. “I’m particularly indebted to the past and present members of the Division of Nephrology at Tufts MC, whose outstanding work has been critical to these advances. We have changed the direction of the field. It’s very fulfilling and satisfying to see our hard work pay off in widespread implementation for public health and clinical benefit.”

Despite all of his accomplishments, Levey is far from satisfied. He is currently part of a group of researchers from Johns Hopkins, the University of Utah and the University of Minnesota who have received multi-year grants from National Institutes of Health to further improve and refine the current tests for estimating kidney function by identifying, evaluating and validating additional, new markers. Levey believes that they will eventually settle on a panel of four-to-seven markers in a single blood test that would be the near-equal of measured GFR.

“As the markers get more accurate, they become increasingly harder to improve,” said Levey. “But even incremental upgrades in the accuracy of GFR tests could affect clinical practice for millions of people. Our current tests are very good, but there’s still work to be done. We are not there yet.”

For more information on CKD or to make an appointment with Dr. Levey, please call 617-636-5866.