Lower phase angle linked to CKD progression in T2DM

A Singapore study has found a previously overlooked connection between bioelectrical impedance analysis (BIA)-derived lower phase angle and chronic kidney disease (CKD) progression, mediated by matrix metalloproteinase-2 (MMP-2), in patients with type 2 diabetes mellitus (T2DM).

“Phase angle may be potentially considered as a safe, inexpensive, and simple marker to predict CKD progression, especially in female patients with T2DM,” the researchers said.

This prospective study included 1,078 T2DM patients (mean age 58.9 years) and used BIA to measure the phase angle. CKD progression was characterized by ≥25-percent decrease in estimated glomerular filtration rate (eGFR) from baseline, with deterioration across eGFR categories.

The researchers used multiplex immunoassay to quantify MMP-2 and Cox proportional hazards model to explore the association between phase angle and CKD, with adjustments for demographics, clinical parameters, and medications.

Of the participants, 43.7 percent had CKD progression over 8.6 years of follow-up. Tertiles 1 and 2 phase angle correlated with a higher risk of CKD progression compared with tertile 3 (tertile 1: unadjusted hazard ratio [aHR], 2.27, 95 percent confidence interval [CI], 1.80‒2.87; p<0.001; tertile 2: aHR, 1.57, 95 percent CI, 1.24‒2.01; p<0.001). [Ann Acad Med Singap 2023;52:125-134]

The positive association of tertiles 1 and 2 phase angle with CKD progression remained in the fully adjusted model (tertile 1: HR, 1.71, 95 percent CI, 1.30‒2.26; p<0.001; tertile 2: HR, 1.46, 95 percent CI, 1.13‒1.88; p=0.004). Notably, MMP-2 was responsible for 14.7 percent of the association between tertile 1 phase angle and CKD progression.

Clinical implications

“Several clinical implications emerged in our current study. Firstly, low phase angle may serve as a risk marker of CKD progression in T2DM. Hence, healthcare providers may consider proactively monitoring renal function in patients with T2DM and low phase angle,” the researchers said.

“Secondly, it is possible to monitor phase angle in routine [diabetes] management since BIA is a convenient, noninvasive, inexpensive, and reliable method to measure body composition. Thirdly, phase angle may be considered a useful indicator for monitoring therapies targeted at slowing down CKD progression in patients with T2DM,” they added. [Am J Clin Nutr 1989;50:221-226]

Furthermore, several studies have reported the effects of high-dose vitamin D supplementation and nutritional counselling, in combination with whey proteins isolate supplementation, on phase angle improvement in patients with cancer. [Cancer Med 2019;8:6923-6932; Nutr Cancer 2021;73:1882-1889]

“Our study results have provided new insights into the increased susceptibility of T2DM patients with low phase angle to CKD progression,” the researchers said. “The novel interplay involving low phase angle, MMP-2, and CKD progression suggests a causal pathway underlying the association between low phase angle and CKD progression, although future studies are needed to confirm the finding.”

This study was limited by the lack of data on nutrition, which could influence the level of phase angle. In addition, results could not be generalized to the general population since the participants consisted of only patients with T2DM. [Nutrients 2021;13:1446]

“Phase angle, derived from BIA, is the angle of vector determined by the body’s resistance and reactance. It indicates cellular integrity and hydration status… MMP-2 is a member of zinc-dependent endopeptidase family and promotes renal interstitial fibrosis.”