Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy

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

doi:10.2337/dc18-1369

Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy

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 PezzolesiSamy Hadjadj, Peter Rossing, Per-Henrik Groop, Andrzej S Krolewski

Institut for Klinisk Medicin

14 Citationer (Scopus)

Abstract

OBJECTIVE Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1–3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3–18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA _1c , and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.

Originalsprog	Engelsk
Tidsskrift	Diabetes Care
Vol/bind	42
Udgave nummer	1
Sider (fra-til)	93-101
Antal sider	9
ISSN	0149-5992
DOI	https://doi.org/10.2337/dc18-1369
Status	Udgivet - 1 jan. 2019

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Skupien, J., Smiles, A. M., Valo, E., Ahluwalia, T. S., Gyorgy, B., Sandholm, N., Croall, S., Lajer, M., McDonnell, K., Forsblom, C., Harjutsalo, V., Marre, M., Galecki, A. T., Tregouet, D-A., Wu, C. Y., Mychaleckyj, J. C., Nickerson, H., Pragnell, M., Rich, S. S., ... Krolewski, A. S. (2019). Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy. Diabetes Care, 42(1), 93-101. https://doi.org/10.2337/dc18-1369

Skupien, J, Smiles, AM, Valo, E, Ahluwalia, TS, Gyorgy, B, Sandholm, N, Croall, S, Lajer, M, McDonnell, K, Forsblom, C, Harjutsalo, V, Marre, M, Galecki, AT, Tregouet, D-A, Wu, CY, Mychaleckyj, JC, Nickerson, H, Pragnell, M, Rich, SS, Pezzolesi, MG, Hadjadj, S, Rossing, P, Groop, P-H & Krolewski, AS 2019, 'Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy', Diabetes Care, bind 42, nr. 1, s. 93-101. https://doi.org/10.2337/dc18-1369

@article{096e5d5de56c459ebcda0a0609fb57a5,

title = "Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy",

abstract = " OBJECTIVE Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1–3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3–18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA 1c , and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes. ",

keywords = "Adult, Albuminuria/urine, Blood Pressure, Cholesterol/blood, Creatinine/blood, Denmark, Diabetes Mellitus, Type 1/blood, Diabetic Nephropathies/blood, Disease Progression, Female, Finland, Follow-Up Studies, France, Glomerular Filtration Rate, Glycated Hemoglobin A/metabolism, Humans, Kidney Failure, Chronic/blood, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors",

author = "Jan Skupien and Smiles, {Adam M} and Erkka Valo and Ahluwalia, {Tarunveer S} and Beata Gyorgy and Niina Sandholm and Stephanie Croall and Maria Lajer and Kevin McDonnell and Carol Forsblom and Valma Harjutsalo and Michel Marre and Galecki, {Andrzej T} and David-Alexandre Tregouet and Wu, {Chun Yi} and Mychaleckyj, {Josyf C} and Helen Nickerson and Marlon Pragnell and Rich, {Stephen S} and Pezzolesi, {Marcus G} and Samy Hadjadj and Peter Rossing and Per-Henrik Groop and Krolewski, {Andrzej S}",

note = "{\textcopyright} 2018 by the American Diabetes Association.",

year = "2019",

month = jan,

day = "1",

doi = "10.2337/dc18-1369",

language = "English",

volume = "42",

pages = "93--101",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "1",

}

TY - JOUR

T1 - Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy

AU - Skupien, Jan

AU - Smiles, Adam M

AU - Valo, Erkka

AU - Ahluwalia, Tarunveer S

AU - Gyorgy, Beata

AU - Sandholm, Niina

AU - Croall, Stephanie

AU - Lajer, Maria

AU - McDonnell, Kevin

AU - Forsblom, Carol

AU - Harjutsalo, Valma

AU - Marre, Michel

AU - Galecki, Andrzej T

AU - Tregouet, David-Alexandre

AU - Wu, Chun Yi

AU - Mychaleckyj, Josyf C

AU - Nickerson, Helen

AU - Pragnell, Marlon

AU - Rich, Stephen S

AU - Pezzolesi, Marcus G

AU - Hadjadj, Samy

AU - Rossing, Peter

AU - Groop, Per-Henrik

AU - Krolewski, Andrzej S

PY - 2019/1/1

Y1 - 2019/1/1

N2 - OBJECTIVE Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1–3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3–18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA 1c , and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.

AB - OBJECTIVE Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts. RESEARCH DESIGN AND METHODS In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1–3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3–18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD. RESULTS During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA 1c , and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes. CONCLUSIONS Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.

KW - Adult

KW - Albuminuria/urine

KW - Blood Pressure

KW - Cholesterol/blood

KW - Creatinine/blood

KW - Denmark

KW - Diabetes Mellitus, Type 1/blood

KW - Diabetic Nephropathies/blood

KW - Disease Progression

KW - Female

KW - Finland

KW - Follow-Up Studies

KW - France

KW - Glomerular Filtration Rate

KW - Glycated Hemoglobin A/metabolism

KW - Humans

KW - Kidney Failure, Chronic/blood

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

U2 - 10.2337/dc18-1369

DO - 10.2337/dc18-1369

M3 - Journal article

C2 - 30455333

SN - 0149-5992

VL - 42

SP - 93

EP - 101

JO - Diabetes Care

JF - Diabetes Care

IS - 1

ER -

Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy

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