Chronic Kidney Disease Definition Likely Inflates Disease Burden

By Marilynn Larkin

September 07, 2021

NEW YORK (Reuters Health) - The current guideline-defined chronic kidney disease (CKD) definition, which does not consider age-related eGFR decline, likely results in overdiagnosis among adults 65 and older, researchers suggest.

"With age, eGFR declines," Dr. Pietro Ravani of the University of Calgary in Alberta told Reuters Health by email. "In the absence of significant albuminuria, the risk of kidney failure is very small when eGFR is 45-59 in the elderly (those ages 65+)," he said. "Classifying these people as diseased will likely cause more harm than benefits, to them and to the system."

"Even if the speed of disease progression is faster when eGFR is 45-60 than when it is >60, the distance travelled (to kidney failure) is very small in both cases," he explained. "The risk of kidney failure at five years - i.e., the percentage of the journey completed - is about 2/1,000 versus 1/1,000 (two versus one 1000th of the distance from the start). This means the two speeds are so slow that neither moves!"

By contrast, he said, "the risk of death at five years in the elderly ranges from 25% to 90%."

As reported in JAMA Internal Medicine, Dr. Ravani and colleagues studied data on adults in Canada diagnosed with CKD from 2009-2017, defined as a sustained reduction in eGFR for longer than three months below a fixed or an age-adapted eGFR threshold.

Non-CKD controls were 65 or older with a sustained eGFR of 60 to 89 mL/min/1.73 m2 for longer than three months and normal/mild albuminuria.

The team used a fixed eGFR threshold of 60 mL/min/1.73 m2 to define CKD, according to current criteria. For the age-adapted definition, they used thresholds of 75 for patients younger than 40; 60 for those ages 40-64; and 45 for those 65 and older.

The primary outcomes were competing risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m2 for >3 months) and death without kidney failure.

The fixed-threshold eGFR cohort included more than 127,000 participants (55% women) and the age-adapted CKD cohort included more than 81,000 (55% women).

The fixed-threshold definition resulted in a 60% higher case incidence rate than the age-adapted definition (537 vs. 343 new cases per 100,000 person-years).

Notably, 75% of those included in the fixed-threshold cohort were 65 or older and had a baseline eGFR of 45 to 59 mL/min/1.73 m2, with normal/mild albuminuria. The five-year risks of kidney failure and death among those participants were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories. However, risk of death was 69, 122, 279, and 935 times higher than the risk of kidney failure for those ages 65-69, 70-74, 75-79, and 80 or older, respectively.

The authors conclude, "These risk profiles suggest that an eGFR of 45 to 59 mL/min/1.73 m2 without albuminuria in elderly individuals may deserve recognition and management strategies to target modifiable risk factors for death but may not have implications for kidney health."

Dr. Ravani added the clinicians should "try to...stop the sensationalism about a CKD epidemic, with associated waste of resources and unnecessary panic for patients."

Dr. Ann O'Hare of the University of Washington and VA Puget Sound Health Care System in Seattle told Reuters Health by email that National Kidney Foundation 2002 guidelines state that adults with a sustained eGFR<60 have CKD. However, "the average level of eGFR (and GFR) approaches 60 in older age groups," she said, "so you can imagine that defining CKD as an eGFR<60 regardless of age is going to capture a large number of older adults with eGFR levels just above and below 60."

Adults over age 65 may meet the criteria for CKD, she said, "but unlike younger adults, they don't have a higher risk of death than people of their age with higher levels of eGFR...so the emphasis on cardiovascular risk reduction and slowing progression to end-stage renal disease doesn't apply to them any more than it does to older adults who have higher levels of eGFR and don't meet criteria for CKD."

"Because the relationship between eGFR and adverse outcomes varies across age groups, it is impossible to find a single eGFR threshold that has the same implications for adults of all ages," she said. "A more nuanced approach is probably needed, perhaps similar to the approach (used in the study)."

SOURCE: https://bit.ly/3kYj9ll and https://bit.ly/3DOw7Ln JAMA Internal Medicine, online August 30, 2021.

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