OR14-4 Early Glomerular Hyperfiltration and Long Term Kidney Outcomes in Type 1 Diabetes: The DCCT/EDIC Experience

INTRODUCTION Glomerular hyperfiltration has long been considered to be a major contributing factor to the development of diabetic kidney disease but most studies assessed increased albumin excretion rather than reduced GFR as an outcome. To address whether early glomerular hyperfiltration results in subsequent increased risk of clinically significant loss of GFR, namely Stage 3 CKD (eGFR <60 ml/min/1.73m(2)), we analyzed 30 year GFR follow-up data in participants undergoing (125)I-iothalamate clearance on entry into the DCCT/EDIC Study. METHODS(125)I-iothalamate clearance was added to the DCCT protocol in 1986 and was assessed at DCCT baseline in 446 participants. This analysis reports long-term eGFR (CKD-EPI equation) follow-up data on these participants. The association of baseline hyperfiltration (primary cutpoint of ≥140 ml/min/1.73m(2)) with the risk of developing Stage 3 CKD (eGFR < 60 ml/min/1.73m(2)) was analyzed using Cox proportional hazards models. RESULTS Of the 446 participants, 178 had iothalamate GFR levels ≥ 130 mL/min/1.73m(2) and of these, 106 had levels ≥ 140 mL/min/1.73m(2) and 55 had levels ≥ 150 mL/min/1.73m(2) upon entry into the DCCT. Among these 446 participants, 53 developed an eGFR < 60 mL/min/1.73m(2) events over a median follow-up time of 28 years (rate of 4.69 events per 1000 individuals at risk for one year), and 34 developed a sustained (i.e., two consecutive visits) eGFR <60 mL/min/1.73m(2) events over a median follow-up time of 28 years (rate of 2.98 sustained events per 1000 individuals at risk for one year) in DCCT/EDIC. The proportion maintaining an eGFR ≥ 60 mL/min/1.73m(2) was not decreased and was actually somewhat greater in the hyperfiltration group (95/106 = 89.6% vs. 298/340 = 87.6%) using the cutoff of 140 mL/min/1.73m(2). The cumulative incidences of developing an eGFR < 60 mL/min/1.73m(2) were again similar in the two hyperfiltration groups (≥140 vs. < 140 mL/min/1.73m(2) - 4.1% vs. 5.9% after 20 years and 11% vs. 12.8% after 28 years). Hyperfiltration as assessed by iothalamate GFR ≥140 mL/min/1.73m(2) was not associated with subsequent risk of developing an eGFR < 60 mL/min/1.73m(2) in an unadjusted Cox PH model (HR= 0.83, 95%CI [0.43, 1.62]) nor in the adjusted model (HR= 0.77, 95%CI [0.38, 1.54]). Similar results were obtained for the developing of a sustained eGFR < 60 mL/min/1.73m(2). Hyperfiltration cut-offs of 130 and 150 ml/min/1.73m(2) showed similar findings. CONCLUSIONS Early hyperfiltration in patients with type 1 diabetes was not associated with any long-term decrease in kidney function. Though it is known with certainty that long-term improved glycemic control reduces the development of microalbuminuria, macroalbuminuria and Stage 3 CKD, the notion that early hyperfiltration is a marker of poor long term renal outcome is not supported by these findings.