Early Glomerular Hyperfiltration and Long-Term Kidney Outcomes in Type 1 Diabetes: The DCCT/EDIC Experience

Abstract

Background and objectives: Glomerular hyperfiltration has been considered to be a contributing factor to the development of diabetic kidney disease (DKD). To address this issue, we analyzed GFR follow-up data on participants with type 1 diabetes undergoing ¹²⁵I-iothalamate clearance on entry into the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study.

Design, setting, participants, & measurements: This was a cohort study of DCCT participants with type 1 diabetes who underwent an ¹²⁵I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltration was defined as iGFR levels ≥140 ml/min per 1.73 m², with secondary thresholds of 130 or 150 ml/min per 1.73 m². Cox proportional hazards models assessed the association between the baseline hyperfiltration status and the subsequent risk of reaching an eGFR <60 ml/min per 1.73 m².

Results: Of the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140 ml/min per 1.73 m²) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m². The cumulative incidence of eGFR <60 ml/min per 1.73 m² at 28 years of follow-up was 11.0% among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73 m². Hyperfiltration was not significantly associated with subsequent risk of developing an eGFR <60 ml/min per 1.73 m² in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjusted model (hazard ratio, 0.77; 95% confidence interval, 0.38 to 1.54). Application of alternate thresholds to define hyperfiltration (130 or 150 ml/min per 1.73 m²) showed similar findings.

Conclusions: Early hyperfiltration in patients with type 1 diabetes was not associated with a higher long-term risk of decreased GFR. Although glomerular hypertension may be a mechanism of kidney injury in DKD, higher total GFR does not appear to be a risk factor for advanced DKD.

Keywords: DCCT/EDIC; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Incidence; Iothalamic Acid; Kidney Glomerulus; Proportional Hazards Models; diabetes mellitus; glomerular filtration rate; glomerular hyperfiltration; hypertension; iothalamate GFR; kidney; risk factors.

Graphical abstract

Figure 1.

Kaplan–Meier survival curves and 95% CIs for developing an eGFR <60 ml/min per 1.73 m² show no difference for those with hyperfiltration (eGFR >140 ml/min per 1.73 m₂) compared to those without hyperfiltration (eGFR <140 ml/min per 1.73 m₂).

Figure 2.

Risk gradient showing the log hazard rate (and 95% pointwise CIs) for the development of an eGFR <60 ml/min per 1.73 m² as a function of the iothalamate GFR.