Difference in eGFR Values Based on Cystatin C vs Creatinine Could Indicate Higher HF Risk

A study published in the American Journal of Kidney Diseases found that in patients with chronic kidney disease (CKD) who had large differences in their glomerular filtration rate (eGFR) values based on cystatin C (eGFR_cys) vs creatinine (eGFR_cr), there was a stronger association between eGFR_cys and incident heart failure.

eGFR measures kidney function and can be determined using either cystatin C or creatinine, but some individuals have differences between their eGFR_cys and their eGFR_cr. Prior research has indicated that having a large difference between the values is associated with outcomes including all-cause mortality, hospitalization, and end-stage kidney disease, but the link between the difference and heart failure hospitalizations has not been established.

This study analyzed data of participants in the Chronic Renal Insufficiency Cohort (CRIC) study. Patients were excluded if they did not have simultaneous serum cystatin C and creatinine measurements from at least 2 study visits within the first 3 years of follow-up, as well as if they had self-reported prevalent heart failure at baseline. Data were also obtained from the National Institute of Diabetes and Digestive and Kidney Diseases repository in April 2021.

The study included 4512 participants, 44% of whom were women, 42% who were non-Hispanic Black, and 11% who were Hispanic. The mean age of the population was 59.4 years, mean eGFR_cys was 55 mL/min/1.73 m², and eGFR_cr was 49 mL/min/1.73 m². The baseline difference between eGFR_cys and eGFR_cr ranged from –52 to 65 mL/min/1.73 m², with a mean (SD) of 6 (16). About two-thirds of the participants had a baseline difference between –15 and 15 mL/min/1.73 m², whereas 7% had a difference of less than –15 and 26% had a difference of at least 15.

Twelve percent of participants developed incident heart failure in the study, with a median (IQR) time of 3.5 (1.5-7.1) years until incident heart failure hospitalization. The researchers found that, after adjusting for demographics, each 15 mL/min/1.73 m² lower baseline difference between eGFR_cys and eGFR_cr was associated with a 56% increase in risk of incident heart failure.

The rate of incident heart failure was found to be highest in participants with a negative difference (ie, eGFR_cys < eGFR_cr) and lowest in participants with a positive difference (ie, eGFR_cys > eGFR_cr). However, neither were statistically significantly associated with heart failure in the multivariable adjusted risk model.

The multivariable adjusted models that accounted for time-updated eGFR difference found that each 15 mL/min/1.73 m² lower baseline eGFR difference was associated with a 36% higher risk of incident heart failure. Participants with a negative eGFR difference had a higher adjusted risk of heart failure (sHR, 1.99; 95% CI, 1.39-2.86) and participants with a positive eGFR difference had a lower adjusted risk (sHR, 0.67; 95% CI, 0.49-0.91).

When accounting for the slope of eGFR difference, the mean (SD) annual change was –0.4 (0.9) mL/min/1.73 m² per year. Each SD lower for eGFR difference slope was associated with a 37% higher risk of incident heart failure. Participants in the first tertile, which had the steepest declines in eGFR_cys compared with eGFR_cr, had a 49% greater risk of incident heart failure hospitalizations.

There were some limitations to this study. Entry into the CRIC was determined by eGFR_cr, which greatly restricted eGFR_cr but not eGFR_cys, which likely excluded participants with a negative eGFR difference. The absolute difference between eGFR_cys and eGFR_cr was used, which constrained the range of eGFR difference at lower values. Cystatin C was also not calibrated to an international standard. There were not sufficient data on ejection fraction at the time of hospitalization for heart failure.

Exacerbations of heart failure that may have been diagnosed in ambulatory settings were not included in this analysis. The slope measurements for eGFR difference were obtained using a joint model. The results of this study may not be generalizable to patients with CKD outside of the United States.

The researchers concluded that differences in eGFR_cys and eGFR_cr were important in conveying information about risk of heart failure hospitalizations.

“In patients with CKD, annual measures of serum creatinine and cystatin C and separate reporting of both eGFR_cys and eGFR_cr would optimize the assessment of [heart failure] risk,” the authors wrote.

Reference

Chen DC, Shlipak MG, Scherzer R, et al. Association of intra-individual differences in estimated GFR by creatinine versus cystatin C with incident heart failure. Am J Kidney Dis. Published online July 8, 2022. doi:10.1053/j.ajkd.2022.05.011