title: Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with Type 1 diabetes.
abstract: BACKGROUND
  Rapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ≥ 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes.
  
  
  METHODS
  GFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years.
  
  
  RESULTS
  Renal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ≥135 mL/min/1.73 m(2) yielded similar results.
  
  
  CONCLUSIONS
  In adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.affiliation: Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Cherney
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Division of Nephrology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA Division of Nephrology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
mesh_terms: D000328:Adult; D001795:Blood Pressure Determination; D002114:Calcinosis / Q000150:complications*; D003324:Coronary Artery Disease / Q000150:complications*; D003404:Creatinine / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000209:etiology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin
keywords: CKD-EPI creatinine and cystatin C; diabetic nephropathy; glomerular filtration rate (GFR); rapid GFR decline; renal hyperfiltration