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Diabetes Care. 2018 Nov 19. pii: dc181369. doi: 10.2337/dc18-1369. [Epub ahead of print]

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.

Author information

1
Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland jan.skupien@uj.edu.pl andrzej.krolewski@joslin.harvard.edu.
2
Research Division, Joslin Diabetes Center, Boston, MA.
3
Folkhälsan Institute of Genetics, Folkhälsan Research Center; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital; and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
4
Steno Diabetes Center Copenhagen, Copenhagen, Denmark.
5
Sorbonne Université UPMC Univ. Paris 06 INSERM UMR_S 1166, and Department of Genomics and Pathophysiology of Cardiovascular Diseases, Institute of Cardiometabolism and Nutrition, Paris, France.
6
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
7
Diabetes Department, Hôpital Bichat-Claude Bernard, Assistance Publique des Hôpitaux de Paris, Université Denis Diderot Paris 7 and INSERM U1138, Paris, France.
8
Institute of Gerontology, University of Michigan Medical School, Ann Arbor, MI.
9
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI.
10
Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
11
JDRF International, New York, NY.
12
Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT.
13
INSERM CIC 1402 and U 1082, and Department of Endocrinology and Diabetology, CHU Poitiers, Poitiers, France.
14
Department of Endocrinology, L'institut du Thorax, CIC 1413 INSERM, CHU Nantes, Nantes, France.
15
University of Copenhagen, Copenhagen, Denmark.
16
Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
17
Research Division, Joslin Diabetes Center, Boston, MA jan.skupien@uj.edu.pl andrzej.krolewski@joslin.harvard.edu.
18
Department of Medicine, Harvard Medical School, Boston, MA.

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, HbA1c, 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.

PMID:
30455333
DOI:
10.2337/dc18-1369

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