Risk Factors for Chronic Kidney Disease Evident Decades Before Diagnosis

Risk Factors for Chronic Kidney Disease Evident Decades Before Diagnosis

Risk factors for many chronic diseases are present well before any signs of a problem. Age, hypertension, ethnicity, diabetes, smoking, low HDL cholesterol, proteinuria, and obesity all have been identified as risk factors for chronic kidney disease (CKD), but most studies have evaluated such risk factors at or near the time of diagnosis. Earlier identification may allow for risk factor modification and disease prevention.

Researchers have now found that certain factors are present and identifiable 30 years or more before a diagnosis of CKD. The findings, which are published in the Journal of the American Society of Nephrology, suggest that obesity, high blood pressure, high triglycerides, and diabetes are key signs of potential kidney problems in the future.

Lifetime risks revealed

To look at risk factors for CKD that may appear well in advance of kidney disease, Caroline S. Fox, MD, MPH, and Gearoid McMahon, MB, BCh, of the National Heart Lung and Blood Institute’s Framingham Heart Study and the Center for Population Studies led a team that examined risk factors in study participants who did and did not develop kidney disease.

“One of the benefits of the Framingham Heart Study is that we have a very long duration of follow-up,” Fox said. “As a result, we are able to look far back in time prior to when individuals develop a disease to examine their risk factors.”

The researchers identified 441 new cases of CKD among participants of the Framingham Heart Study, and they matched them with 882 controls who did not develop CKD. Those who ultimately developed CKD were 76 percent more likely to have had hypertension, 71 percent more likely to have been obese, and 43 percent more likely to have had higher triglycerides 30 years before CKD diagnosis.

They were also 38 percent more likely to have had hypertension, 35 percent more likely to have had higher triglyceride levels, and nearly three times more likely to have had diabetes 20 years before CKD diagnosis. There was a graded increase in CKD risk with each additional risk factor in any combination, indicating that the more risk factors an individual had in the past, the more likely they were to develop kidney disease.

Mechanisms and implications

Fox and her colleagues explored the potential mechanisms behind the links they found. For example, regarding dyslipidemia, research indicates that the accumulation of both triglycerides and the breakdown products of lipid metabolism in the blood have atherogenic and pro-inflammatory effects on the vasculature in the kidney. Obesity is also known to have detrimental effects on the kidneys, and studies have pointed to histopathological changes of obesity-related glomerulopathy in obese patients with no evidence of renal disease. Also, weight loss in patients with obesity-related kidney disease has been linked with reduced glomerular hyperfiltration and albuminuria.

The authors stressed that their observational study does not show whether altering these risk factors will definitely prevent future disease. Therefore, future studies should focus on whether early risk factor modification will decrease the incidence of CKD. Another important limitation is that the population studied was exclusively European-American, which indicates that the results may not be generalizable to the entire population.

Others in the field noted the value of uncovering early indications of CKD decades before disease onset.

“This is an important study because it provides further evidence that CKD is a life course illness that often develops over several decades. The observation that risk factors such as hypertension, obesity, dyslipidemia, and diabetes may be present two to three decades before the detection of CKD implies that early intervention to abrogate these risk factors may be effective in reducing the prevalence of CKD,” said Maarten Taal, MD, FCP(SA), FRCP, a professor of medicine at the University of Nottingham and an honorary consultant nephrologist and lead clinician within the renal unit at the Royal Derby Hospital, in the UK. “This is important because of the high prevalence of CKD that affects up to 15 percent of the adult population and because of the relative ineffectiveness of currently available therapies to ameliorate the associated risks of progressive kidney damage and cardiovascular disease.”

Taal noted that the risk factors identified are equally important for cardiovascular disease prevention, so programs focused on cardiovascular risk reduction in the general population should also reduce kidney-related risks.

Study co-authors include Sarah Preis, ScD, PhD, and Shih-Jen Hwang, PhD.
Disclosures: The authors reported no financial disclosures.
The article, entitled “Mid-Adulthood Risk Factor Profiles for CKD,” is online at http://jasn.asnjournals.org/.