A synergistic effect of variability in estimated glomerular filtration rate with chronic kidney disease on all-cause mortality prediction in patients with type 2 diabetes: a retrospective cohort study

Abstract

Background The combination of diabetes mellitus (DM) and chronic kidney disease (CKD) is associated with a high risk of mortality. Annual assessment of the estimated glomerular filtration rate (eGFR) is recommended for patients with DM. We investigated the effect of variability in annual eGFR values on all-cause mortality in patients with type 2 DM. Methods In this retrospective cohort study, we enrolled patients with eGFR data between 01 Aug 2017 and 31 July 2018. We defined the index eGFR as the first available eGFR value within the enrollment year and collected additional annual eGFR data from the previous three years. A total of 3592 patients with type 2 DM were enrolled, including 959 patients with CKD (index eGFR < 60 mL/min/1.73 m2) and 2633 patients without CKD. We assessed eGFR variability by using the standard deviation (SD) of the three annual eGFR and index eGFR values. We divided patients into subgroups according to the median SD of their annual eGFR (7.62 mL/min/1.73 m2). The primary endpoint was all-cause mortality after the index eGFR was assessed. Results During a median follow-up of 19 months (interquartile range: 18‒20 months), 127 (3.5%) deaths occurred among all 3592 enrolled patients. The highest mortality risk was observed in the high SD with CKD group, with a hazard ratio (HR) of 2.382 [95% confidence interval (CI) 1.346‒4.215] in comparison to the low SD without CKD group after adjusting for the associated factors. In patients without CKD, a high SD was an independent risk factor for mortality (HR = 2.105, 95% CI 1.256‒3.528). According to the C-index, the mortality prediction ability was better for the index eGFR + SD model than for the index eGFR alone model (0.671 vs. 0.629, P < 0.001). Conclusion There was a synergistic effect of eGFR variability with single-measured eGFR for the prediction of mortality in patients with type 2 DM. The SD of the annual eGFR values was also an independent predictor of mortality in patients with an eGFR > 60 mL/min/1.73 m2.

Association between higher variability in kidney function and long‐term mortality

“…Patients aged ≥60 years in the T3 group showed a higher HR of 1.583. Age itself is an important factor in mortality, but like some studies on eGFR variability have reported, it can also be a risk factor for eGFR variability 20,23 . Patients with diabetes in the T3 group showed a pattern of a more significant increase in all‐cause mortality compared to non‐DM patients.…”

“…Circulating glucose could affect the renal hemodynamic change and eGFR variability, 28 and defective autoregulation in patients with diabetes may have also induced higher eGFR variability and increased mortality. 20,29 As shown in the baseline characteristics (Table 1), a negative eGFR slope was more frequent in the third eGFR CV tertile group and was associated with eGFR variability (Table 4). Furthermore, a negative slope was associated with an increased risk of mortality.…”

“…The eGFR decline and variability was higher in males than in females in some studies 13,23 . DM, HTN, and proteinuria are well known risk factors for kidney disease; thus, it is not surprising that these factors were associated with eGFR variability 20,24,25 . We evaluated whether these factors were also associated with mortality and eGFR variability.…”

“…7 The mechanism by which eGFR variability affects mortality is not well understood; however, it can be assumed that it is similar to the mechanism by which eGFR variability worsens renal function, that is, by an inflammatory reaction and renin-angiotensin system activation. 12,20 In practice, eGFR variability is commonly observed. It may change depending on the weight, BMI, renal mass or renal flow, BP, drugs, and even circadian rhythm of the patient.…”

“…13,23 DM, HTN, and proteinuria are well known risk factors for kidney disease; thus, it is not surprising that these factors were associated with eGFR variability. 20,24,25 We evaluated whether these factors were also associated with mortality and eGFR variability. Smoking and alcohol intake were associated with eGFR variability, while DM and HTN were not.…”