Kidney measures for CKD predict clinical risk across the full age range

Measures of kidney function used to diagnose and stage chronic kidney disease (CKD) are independently associated with end-stage renal disease (ESRD) and mortality regardless of age, according to a new study.

Researchers performed an individual-level meta-analysis of over two million people to determine whether age modified the association of estimated glomerular filtration rate (eGFR) and albuminuria with ESRD and death. Both relative and absolute risks were evaluated. The meta-analysis looked at hazard ratios (HRs) of the primary end points, all-cause mortality and ESRD, according to eGFR and albuminuria by age category; data were adjusted for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol level, body mass index and smoking status. HRs and average incidence rates were used to determine absolute risks. Results were published online Oct. 30 by the Journal of the American Medical Association.

Participants from the Chronic Kidney Disease Prognosis Consortium, which is made up of 33 general population cohorts and 13 CKD cohorts in Asia, Australasia, Europe and North and South America, were included. Patients were followed for a mean of 5.8 years between 1972-2011. The mean patient age was 49.4 years, and 7.3% of patients were older than age 75.

Deaths (112,325 people) and ESRD (8,411 events) were higher in patients with lower eGFR and higher albuminuria in every age category. In both general and high-risk cohorts, relative mortality risk decreased with increasing age for reduced eGFR (adjusted HRs, 3.50 [95% CI, 2.55 to 4.81], 2.21 [95% CI, 2.02 to 2.41], 1.59 [95% CI, 1.42 to 1.77], and 1.35 [95% CI, 1.23 to 1.48] for an eGFR of 45 mL/min/1.73 m² vs. 80 mL/min/1.73 m² in patients age 18 to 54 years, 55 to 64 years, 65 to 74 years, and ≥75 years, respectively; P<0.05 for age interaction). Absolute risk differences increased with age for the same comparisons (9.0 excess deaths per 1,000 person-years [95% CI, 6.0 to 12.8], 12.2 excess deaths per 1,000 person-years [95% CI, 10.3 to 14.3], 13.3 excess deaths per 1,000 person-years [95% CI, 9.0 to 18.6], and 27.2 excess deaths per 1,000 person-years [95% CI, 13.5 to 45.5], respectively).

Reduced relative risk with increasing age was less marked for increased albuminuria. However, absolute risk differences were higher by older age category: 7.5 excess deaths per 1,000 person-years (95% CI, 4.3 to 11.9), 12.2 excess deaths per 1,000 person-years (95% CI, 7.9 to 17.6), 22.7 excess deaths per 1,000 person-years (95% CI, 15.3 to 31.6), and 34.3 excess deaths per 1,000 person-years (95% CI, 19.5-52.4), respectively, for an albumin-creatinine ratio of 300 mg/g compared with 10 mg/g. Adjusted relative hazards of mortality did not decrease with age in cohorts of patients with CKD, and in all cohorts, relative risks and absolute risk differences for ESRD at lower eGFRs or higher albuminuria values were comparable by age.

The authors noted that serum creatinine measurements were not standardized among studies, that no gold standard exists for measuring urine albumin, that the cohorts were heterogeneous, and that their results are based on models adjusted for traditional risk factors and therefore require careful interpretation. However, they concluded, “Although some variation in management of CKD should be considered by age based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staggering of CKD based on eGFR and albuminuria for all age groups.”

The author of an accompanying editorial wrote that older adults with CKD are at high risk for death, usually from cardiovascular disease, and that clinicians should make every effort to offer proven treatment strategies in this population.

“Preventing progression of CKD may be an important goal in some patients, but most older patients with CKD will not progress to ESRD,” the author wrote. He also stressed that some treatments that are effective in middle-aged adults with normal kidneys may have different benefits and risks, especially drug-related adverse effects, in older patients. “To move forward,” he wrote, “CKD identification must be coupled with new treatment strategies tailored to patients with CKD, including older patients with CKD.”