Abstract
BACKGROUND AND OBJECTIVES: Hyperfiltration at the single-nephron level has been proposed as an early stage of kidney dysfunction of different origins. Evidence supporting this hypothesis in humans is lacking, because there is no method of measuring single-nephron GFR in humans. However, increased whole-kidney GFR in the same individual implies an increased single-nephron GFR, because the number of nephrons does not increase with age. We hypothesized that an increase in GFR would be associated with an increased albumin-to-creatinine ratio in a cohort of the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured GFR by iohexol clearance at baseline in 2007-2009 and follow-up after 5.6 years in a representative sample of 1246 persons (aged 50-62 years) who were nondiabetic from the general population of Tromso, northern Norway. Participants were without cardiovascular disease, kidney disease, or diabetes at baseline. We investigated the association between change in GFR and change in albumin-to-creatinine ratio. Increased GFR was defined as a positive change in GFR (change in GFR>0 ml/min) from baseline to follow-up. An albumin-to-creatinine ratio >30 mg/g was classified as albuminuria. RESULTS: Change in GFR was positively associated with a change in albumin-to-creatinine ratio in the entire cohort in the multiple linear regression. The albumin-to-creatinine ratio(follow-up)-to-albumin-to-creatinine ratio(baseline) ratio increased by 8.0% (95% confidence interval, 1.4 to 15.0) per SD increase in change in GFR. When participants with increased GFR (n=343) were compared with those with a reduced GFR (n=903), the ratio increased by 16.3% (95% confidence interval, 1.1 to 33.7). The multivariable adjusted odds ratio for incident albuminuria (n=14) was 4.98 (95% confidence interval, 1.49 to 16.13) for those with an increased GFR (yes/no). CONCLUSIONS: Increasing GFR is associated with an increase in albumin-to-creatinine ratio and incident albuminuria in the general nondiabetic population. These findings support single-nephron hyperfiltration as a risk factor for albuminuria in the general population.