title: Patterns of Estimated Glomerular Filtration Rate Decline Leading to End-Stage Renal Disease in Type 1 Diabetes.
abstract: The patterns of estimated glomerular filtration rate (eGFR) decline to end-stage renal disease (ESRD) in patients with type 1 diabetes has not been conclusively described. Decline could be linearly progressive to ESRD but with a variable rate. Conversely, decline may be linear but interrupted by periods of plateaus or improvements.
  
  
  
  This observational study included 364 patients with type 1 diabetes attending the Joslin Clinic who developed ESRD between 1991 and 2013. We retrieved serum creatinine measurements from clinic visits or research examinations up to 24 years (median 6.7 years) preceding the onset of ESRD. Using serial measurements of serum creatinine to estimate renal function (eGFR), we used regression-based spline methods and a data smoothing approach to characterize individual trajectories of eGFR over time for the 257 patients with five or more data points.
  
  
  
  The rate of eGFR decline per year ranged widely, from -72 to -2 mL/min/1.73 m2(median -8.5). The trajectories, as characterized with linear regression-based spline models, were linear or nearly so for 87% of patients, accelerating for 6%, and decelerating for 7%. Smoothed trajectories evaluated by a Bayesian approach did not significantly depart from a linear fit in 76%.
  
  
  
  The decline of eGFR in type 1 diabetes is predominantly linear. Deviations from linearity are small, with little effect on the expected time of ESRD. A single disease process most likely underlies renal decline from its initiation and continues with the same intensity to ESRD. Linearity of renal decline suggests using slope reduction as the measure of effectiveness of interventions to postpone ESRD.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA andrzej.krolewski@joslin.harvard.edu jan.skupien@uj.edu.pl.|Department of Medicine, Harvard Medical School, Boston, MA.|Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Smiles
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA.|Department of Medicine, Harvard Medical School, Boston, MA.|Renal Division at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Stanton
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA andrzej.krolewski@joslin.harvard.edu jan.skupien@uj.edu.pl.|Department of Medicine, Harvard Medical School, Boston, MA.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors