Certain Kidney Function Measures May Determine Long-Term Physical Function Decline


Understanding long-term frailty trajectories with kidney function measures could help prevent worse adverse health outcomes in older patients.

New research indicates an association between faster and worse rates of physical function and cystatin C level, cystatin C estimated glomerular filtration rate (eGFRcys), and the difference between eGFRs (eGFRdiff). These kidney function measures could indicate long-term deficit-accumulation frailty trajectories, according to the study, published in JAMA Network Open.

“This study’s findings suggest that, among community-dwelling older people without frailty, monitoring kidney function using cystatin C could provide additional insight into identifying the risk of accelerated frailty progression and physical function decline,” the authors wrote.

Frailty, defined as either an accumulation of deficits or a physical phenotype, worsens with age and is associated with mortality, hospitalization, and falls. Worsening physical function is a phenotype that is associated with frailty progression. Understanding frailty and possible modifiable risk factors in the long-term could help create effective preventative strategies against its adverse outcomes.

Cystatin C can indicate kidney function. Creatinine estimated glomerular filtration rate (eGFRcr) looks at muscle mass to indicate kidney function, but the eGFRcys does not need to. The difference between eGFRcr and eGFRcys is the eGFRdiff. When this is negative, it may be associated with a worse long-term frailty trajectory among older adults.

Researchers set out to understand the prospective association between measures of kidney function (cystatin C serum levels, eGFRcys, eGFRcys) and long-term frailty trajectories.

The investigative team looked at 15,994 older community-dwelling participants from 2 ongoing nationally representative cohort studies from China (China Health and Retirement Longitudinal Study [CHARLS]), and the United States (US Health and Retirement Study [HRS]). At baseline, participants did not have frailty.

“Serum cystatin C level, eGFRcys, and eGFRdiff were associated with accelerated deficit-accumulation frailty trajectories and faster decreases in physical function measurements,” the study authors wrote.

The investigative team suggests cystatin C could be a better marker than creatine because it does not have any racial disparities. It might also be superior at assessing kidney function and the risk of accelerated frailty/physical function decline.

The findings from this study were consistent with previous research, which found associations between frailty, frailty incidence rate, and eGFRcys. However, the current study went beyond previous research, also identifying eGFRdiff as having a possible association with declining physical function. However, higher levels of eGFRdiff were associated with a slower decrease in physical function, which translates to a slower development of frailty over the long term.

Researchers did not measure GFR using criterion-standard, which limited the study. Additionally, there was possible selection bias and heterogeneity, which prevented researchers from pooling the analysis and generalizing findings. Finally, there was potential information bias and confounding because it was an observational study.

“We were able to evaluate long-term dynamic frailty trajectories based on multiple repeated measurement,” the study authors wrote. “Our findings were robust, with similar results observed in various sensitivity analyses… Monitoring kidney function using cystatin C could have clinical utility in identifying the risk of accelerated frailty progression.”


Li, Chenglong, Ma, Yanjun, Yang, Chao, et al. Association of Cystatin C Kidney Function Measures With Long-term Deficit-Accumulation Frailty Trajectories and Physical Function Decline. JAMA Netw Open. 2022;5(9):e2234208. doi:10.1001/jamanetworkopen.2022.34208

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