Jan Skupien1,2,3, James H Warram4,2, Adam M Smiles4,2, Robert C Stanton4,2,5, Andrzej S Krolewski1,2. 1. Research Division, Joslin Diabetes Center, Boston, MA andrzej.krolewski@joslin.harvard.edu jan.skupien@uj.edu.pl. 2. Department of Medicine, Harvard Medical School, Boston, MA. 3. Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland. 4. Research Division, Joslin Diabetes Center, Boston, MA. 5. Renal Division at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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: Elizabeth T Rosolowsky; Jan Skupien; Adam M Smiles; Monika Niewczas; Bijan Roshan; Robert Stanton; John H Eckfeldt; James H Warram; Andrzej S Krolewski Journal: J Am Soc Nephrol Date: 2011-02-25 Impact factor: 10.121
Authors: Kim C Donaghue; Jan M Fairchild; Maria E Craig; Albert K Chan; Stephen Hing; Lucy R Cutler; Neville J Howard; Martin Silink Journal: Diabetes Care Date: 2003-04 Impact factor: 19.112
Authors: S P Laing; A J Swerdlow; S D Slater; A C Burden; A Morris; N R Waugh; W Gatling; P J Bingley; C C Patterson Journal: Diabetologia Date: 2003-05-28 Impact factor: 10.122
Authors: Linda H Ficociello; Bruce A Perkins; Bijan Roshan; Janice M Weinberg; Ann Aschengrau; James H Warram; Andrzej S Krolewski Journal: Diabetes Care Date: 2009-02-05 Impact factor: 19.112
Authors: Andrzej S Krolewski; Monika A Niewczas; Jan Skupien; Tomhito Gohda; Adam Smiles; Jon H Eckfeldt; Alessandro Doria; James H Warram Journal: Diabetes Care Date: 2013-08-12 Impact factor: 19.112
Authors: Masayuki Yamanouchi; Jan Skupien; Monika A Niewczas; Adam M Smiles; Alessandro Doria; Robert C Stanton; Andrzej T Galecki; Kevin L Duffin; Nick Pullen; Matthew D Breyer; Joseph V Bonventre; James H Warram; Andrzej S Krolewski Journal: Kidney Int Date: 2017-04-07 Impact factor: 10.612
Authors: Natalia Nowak; Jan Skupien; Adam M Smiles; Masayuki Yamanouchi; Monika A Niewczas; Andrzej T Galecki; Kevin L Duffin; Matthew D Breyer; Nick Pullen; Joseph V Bonventre; Andrzej S Krolewski Journal: Kidney Int Date: 2018-02-02 Impact factor: 10.612
Authors: Marco Colombo; Erkka Valo; Stuart J McGurnaghan; Niina Sandholm; Luke A K Blackbourn; R Neil Dalton; David Dunger; Per-Henrik Groop; Paul M McKeigue; Carol Forsblom; Helen M Colhoun Journal: Diabetologia Date: 2019-06-20 Impact factor: 10.122
Authors: Cynthia J Janmaat; Merel van Diepen; Cheyenne Ce van Hagen; Joris I Rotmans; Friedo W Dekker; Olaf M Dekkers Journal: Clin Epidemiol Date: 2018-05-25 Impact factor: 4.790
Authors: Jan Skupien; Adam M Smiles; Erkka Valo; Tarunveer S Ahluwalia; Beata Gyorgy; Niina Sandholm; Stephanie Croall; Maria Lajer; Kevin McDonnell; Carol Forsblom; Valma Harjutsalo; Michel Marre; Andrzej T Galecki; David-Alexandre Tregouet; Chun Yi Wu; Josyf C Mychaleckyj; Helen Nickerson; Marlon Pragnell; Stephen S Rich; Marcus G Pezzolesi; Samy Hadjadj; Peter Rossing; Per-Henrik Groop; Andrzej S Krolewski Journal: Diabetes Care Date: 2018-11-19 Impact factor: 19.112