The Association Between Metabolic Syndrome, Hyperfiltration, and Long-Term GFR Decline in the General Population

One-quarter of adults worldwide meet the criteria of metabolic syndrome (MetS). MetS increases the risk of diabetes, chronic kidney disease (CKD), and cardiovascular disease. However, the association between MetS, hyperfiltration, and long-term glomerular filtration rate (GFR) decline in the general population is unknown.

In the Renal Iohexol Clearance Survey (RENIS), we investigated 1551 people aged 50 to 63 years; representative of the general population without diabetes, cardiovascular disease, or kidney disease. The GFR was measured using iohexol clearance at baseline and twice during 11 years of follow-up. Hyperfiltration at baseline was defined as an absolute GFR (ml/min) above the 90th percentile adjusted for sex, age, and height, because these variables correlate with nephron number. MetS was defined as increased waist circumference and 2 risk factors among hypertension, hyperglycemia, elevated triglycerides, and low high density lipoprotein (HDL)-cholesterol levels. The GFR decline rate was calculated using linear mixed models.

MetS was associated with hyperfiltration at baseline (odds ratio [OR] 2.4; 95% CI: 1.7-3.5, P < 0.001) and a steeper GFR decline rate during follow-up (-0.30 [-0.43 to -0.16] ml/min per 1.73 m²/yr). Compared to those without MetS, GFR decline was -0.83 (95% CI: -1.13 to -0.53) ml/min per 1.73 m²/yr in those with MetS and baseline hyperfiltration and -0.15 (-0.30 to 0.00) in those MetS without hyperfiltration, P = 0.2 for interaction.

In the nondiabetic general population, those with MetS had an increased OR of hyperfiltration and steeper long-term GFR decline. Randomized controlled trials are needed to explore whether treatment of hyperfiltration can prevent loss of GFR in persons with MetS.