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 Thiswas a cohort study of DCCT participants with type 1 diabetes whounderwent an 125I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltrationwas 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 ≥140ml/min per 1.73 m2) at baseline. Over amedian follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73m2. The cumulative incidence of eGFR <60 ml/min per 1.73m2 at 28 years of follow-upwas 11.0%among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73m2.Hyperfiltrationwas 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 adjustedmodel (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. ConclusionsEarlyhyperfiltrationinpatientswithtype 1 diabeteswasnot associatedwithahigher long-termriskof 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.