TOPLINE: 

Patients with chronic kidney disease (CKD) whose albuminuria levels are within normal ranges < 30 mg/g still show a linear increase in the risk for CKD progression as albuminuria levels increase from 0.

The findings suggest that clinicians should not necessarily assume that albuminuria levels < 30 mg/g are normal and don’t require therapeutic intervention.

METHODOLOGY:

• The study included 1629 participants at seven US centers in the prospective CRIC study who had CKD, defined as an estimated glomerular filtration rate (eGFR) of 20-70 mL/min/1.73 m² and who had a urine albumin–creatinine ratio (UACR) < 30 mg/g.
• The 10-year adjusted cumulative incidence of CKD progression, a composite of 50% eGFR decline or kidney failure, was determined on the basis of adjusted survival curves.
• Patients were stratified on the basis of UACR levels of 0-5 mg/g, 5 to < 15 mg/g, and ≥ 15 mg/g.
• Over a median of a 9.8-year follow-up, 182 of the 1629 patients had progression of CKD.

TAKEAWAY:

• A linear association was observed between increases in UACR incidence within the 0-30 mg/g range and CKD progression: In the 0 to < 5 mg/g group, the adjusted cumulative incidence of CKD progression was 8.7%; in the 5-15 mg/g group, the rate was 11.5; and in the 15-30 mg/g group, the rate increased to 19.5%.
• Compared with patients with a UACR of ≥ 15 mg/g, those with levels of 5-15 mg/g had an absolute risk difference of 7.9%, and the difference of ≥ 15 mg/g compared with the CKD progression in the 0 to < 5 mg/g, the absolute risk difference of was 10.7%.
• The results were consistent when comparing patients with UACR of ≥ 10 mg/g with those with UACR of < 10 mg/g.
• The linear association was observed independent of factors including baseline kidney function.

IN PRACTICE:

Clinicians may be misled by conventional recommendations suggesting that the risk for CKD progression primarily increases when UACR rises > 30 mg/g, the authors cautioned.

“Our study highlights that those higher levels of albuminuria below 30 mg/g still confer substantially increased risks for CKD progression and subsequent kidney failure in persons with CKD,” they wrote.

“These findings raise an important question of whether any categorizations of albuminuria should remain in clinical and research practice or whether this concept should be replaced by using albuminuria as a risk factor for adverse clinical outcomes on a continuous scale,” the authors added.

Importantly, 63.5% of patients in the study were already receiving antiproteinuric therapy in the form of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at baseline, the authors noted.

Therefore, “our findings further underscore that there is residual risk even for persons with CKD receiving ACE inhibitors or ARB therapy who have higher levels of albuminuria in the normoalbuminuric range.”

SOURCE:

The study was published on April 1, 2024, in Annals of Internal Medicine. The first author is Ashish Verma, MB, BS, of the Boston University Chobanian & Avedisian School of Medicine in Boston, Massachusetts.

LIMITATIONS:

Patients only had UACR levels measured at a single timepoint at baseline, and the study cannot account for day-to-day variability.

While the study adjusted for ACE inhibitor and ARB use, the duration of use could not be assessed, which could alter levels of albuminuria.

DISCLOSURES:

The authors had no disclosures to report.