Risk of chronic kidney disease defined by decreased estimated glomerular filtration rate in individuals with different prediabetic phenotypes: results from a prospective cohort study in China

Abstract

Objective: We aimed to investigate the effects of prediabetes and its phenotypes of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycated hemoglobin A₁c (EHbA_1c) on chronic kidney disease (CKD) occurrence, and define the cut-off point of each glycemic index that significantly increases the risk of CKD.

Research design and methods: In this prospective cohort study, 6446 non-diabetic subjects aged 40 years and over were followed over a period of 3 years to track the new onset of CKD. Cox regression was used to assess the association of prediabetes and its phenotypes with CKD. Receiver operating characteristic curves were used to define the cut-off point of each glycemic index that significantly increases the occurrence of CKD. Population attributable risk percent was calculated to estimate the contribution of prediabetes to CKD.

Results: Compared to subjects with normal glucose tolerance, patients with prediabetes significantly increased the risk of development of CKD (HR=2.33 (1.19-4.55)). Specifically, this increased risk of CKD development was observed in patients with IFG, IGT and EHbA_1c. The cut-off points shown to significantly increase the risk of CKD are fasting plasma glucose of 5.63 mmol/L, 2-hour plasma glucose of 6.80 mmol/L and HbA_1c of 5.6%. The contribution of prediabetes to CKD occurrence in the study population was 60.6%.

Conclusions: This result suggests that the stricter criteria might be needed to define normal plasma glucose level in China that would not be predisposed to diabetic complications, particularly CKD.

Keywords: HbA1c; chronic kidney disease; population-based studies; prediabetes.

Figure 1

Study flow diagram. CKD, chronic kidney disease; NGT, normal glucose tolerance.

Figure 2

Sensitivity analysis of the risk of CKD occurrence in prediabetes at baseline. (A) Stratified the participants into isolated glycemic phenotype of isolated IFG, isolated IGT, isolated EHbA_1c, respectively; (B) using the WHO/IEC criteria to define prediabetes and its phenotypes; (C) using modified MDRD equation to calculate eGFR and define CKD. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; EHbA_1c, elevated glycated hemoglobin A1c; IEC, International Expert Committee; IFG, impaired fasting glucose; IGT: impaired glucose tolerance; MDRD, Modification of Diet in Renal study; NGT, normal glucose tolerance.