CKD Risk Factors Present Decades Prior to Diagnosis

Hypertension, obesity, and higher triglycerides predicted development of CKD 30 years later.
Hypertension, obesity, and higher triglycerides predicted development of CKD 30 years later.

Risk factors for chronic kidney disease (CKD) are identifiable 30 years or more before the diagnosis of CKD, according to recently published findings.

Researchers led by Caroline S. Fox, MD, MPH, of the National Heart, Lung, and Blood Institute's Framingham Heart Study in Framingham, Mass., conducted a case-control study using data from the Framingham Offspring Study. During follow-up, Dr. Fox and her colleagues identified 441 new cases of CKD and matched these cases to 882 controls without CKD.

Compared with controls, participants who eventually developed CKD had a significant 76%, 71%, and 43% greater likelihood of having hypertension, obesity (body mass index 30 kg/m2 or higher), and higher triglyceride levels, respectively, 30 years before their CKD diagnosis, the researchers reported online ahead of print in the Journal of the American Society of Nephrology.

Additionally, the CKD patients had a significant 38% and 35% greater likelihood of having hypertension and higher triglyceride levels, respectively, and a significant 2.9 times greater likelihood of having diabetes 20 years before their CKD diagnosis. They were not significantly more likely to have obesity.

“Our results suggest that CKD should be considered a life course disease,” the investigators wrote. “Identifying individuals at increased risk of CKD early in life may allow interventions that reduce the risk of CKD. In particular, individuals with multiple risk factors could be targeted for more aggressive risk factor management.”

Dr. Fox's group noted that up to 15% of adults in the United States are estimated to CKD, which confers an increased risk of cardiovascular and all-cause mortality. Risk factors for CKD have been well characterized, they pointed out, but most studies have evaluated risk factor profiles at or near the time of CKD diagnosis.

The finding of that obesity did not predict CKD at time points closer to CKD diagnosis supports recent data “suggesting that obesity in early adulthood was more strongly associated with CKD in later life than obesity that developed later. It is possible that the duration of exposure to this risk factor could play an important role in determining the magnitude of the association with CKD.”

The researchers defined CKD as an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or less. The CKD patients had a mean age of 69.2 years at diagnosis. Their median eGFR at diagnosis was 54.2 mL/min/1.73 m2.

Dr. Fox's team noted that the extensive phenotyping and long follow-up of the Framingham Offspring Study is a key strength of the current investigation. “The participants were relatively young at the time of entry into the study and were followed for up to 30 years, which allows us to generalize our results across a wide age range.”

They also pointed out some study limitations. The cohort was entirely of European ancestry, which may limit the generalizability of results to other ethnic or racial groups, they noted. Further, the observational design of the study prevented them from inferring causality.

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