Prediabetes and Risk of Glomerular Hyperfiltration and Albuminuria in the General Nondiabetic Population: A Prospective Cohort Study

Abstract

Background: The role of prediabetes as a risk factor for hyperfiltration and albuminuria in persons who do not develop diabetes is unclear. The lack of evidence is mainly due to the difficulty of accurately assessing the glomerular filtration rate (GFR) in the near-normal range of GFR. We investigated whether prediabetes is an independent risk factor for glomerular hyperfiltration and high-normal urinary albumin-creatinine ratio (ACR) using measured GFR (mGFR) rather than estimated GFR.

Study design: Prospective cohort study based on the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6) and the RENIS Follow-Up Study. Median observation time was 5.6 years.

Setting & participants: A representative sample of 1,261 persons without diabetes mellitus (DM) from the general population aged 50 to 62 years.

Predictor: Prediabetes defined by fasting glucose and hemoglobin A1c according to levels suggested by the American Diabetes Association (preDMADA) and the International Expert Committee of 2009 (preDMIEC).

Outcomes: Change in mGFR; hyperfiltration defined as mGFR>90th percentile adjusted for age, sex, weight, and height; and high-normal ACR (>10mg/g) at follow-up.

Measurements: GFR was measured with iohexol clearance.

Results: Baseline fasting glucose, hemoglobin A1c, and both definitions of prediabetes were predictors of higher mGFR at follow-up and lower annual mGFR decline in multivariable-adjusted regression analyses. Participants with preDMIEC had an OR for hyperfiltration of 1.95 (95% CI, 1.20-3.17) and for high-normal ACR of 1.83 (95% CI, 1.04-3.22) at follow-up. We adjusted for cardiovascular risk factors including ambulatory blood pressure at baseline and change in use of antihypertensive medication between baseline and follow-up.

Limitations: Only middle-aged white patients participated. There is no consensus on how to define glomerular hyperfiltration.

Conclusions: Our findings imply an independent role of prediabetes in the development of glomerular hyperfiltration and albuminuria. Prediabetes might be a target for early treatment to prevent chronic kidney disease in chronic hyperglycemia.

Keywords: HbA(1c); Prediabetes; Tromsø study; albumin-creatinine ratio (ACR); albuminuria; chronic hyperglycemia; estimated GFR; fasting glucose; glomerular filtration rate (GFR); hyperfiltration; iohexol clearance; measured GFR; modifiable risk factor; renal disease.