The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes

Abstract

Objectives: This study aimed to identify clinical features associated with premature mortality in a large contemporary cohort of adults with type 1 diabetes.

Research design and methods: The Finnish Diabetic Nephropathy (FinnDiane) study is a national multicenter prospective follow-up study of 4,201 adults with type 1 diabetes from 21 university and central hospitals, 33 district hospitals, and 26 primary health care centers across Finland.

Results: During a median 7 years of follow-up, there were 291 deaths (7%), 3.6-fold (95% CI 3.2-4.0) more than that observed in the age- and sex-matched general population. Excess mortality was only observed in individuals with chronic kidney disease. Individuals with normoalbuminuria showed no excess mortality beyond the general population (standardized mortality ratio [SMR] 0.8, 95% CI 0.5-1.1), independent of the duration of diabetes. The presence of microalbuminuria, macroalbuminuria, and end-stage kidney disease was associated with 2.8, 9.2, and 18.3 times higher SMR, respectively. The increase in mortality across each stage of albuminuria was equivalent to the risk conferred by preexisting macrovascular disease. In addition, the glomerular filtration rate was independently associated with mortality, such that individuals with impaired kidney function, as well as those demonstrating hyperfiltration, had an increased risk of death.

Conclusions: An independent graded association was observed between the presence and severity of kidney disease and mortality in a large contemporary cohort of individuals with type 1 diabetes. These findings highlight the clinical and public health importance of chronic kidney disease and its prevention in the management of type 1 diabetes.

FIG. 1.

Survival plots showing Cox-adjusted survival of individuals with type 1 diabetes from the FinnDiane study, stratified for the presence and severity of albuminuria (A), estimated GFR (B), and the presence and severity of retinopathy (C) at baseline. All figures are adjusted for age; sex; duration of diabetes; body habitus; the presence and extent of macro- and microvascular complications; glycemic, lipid, and blood pressure control; and drug management. The latter figure (C) is not adjusted for the presence and severity of nephropathy, as discussed in the text.

FIG. 2.

Risk of mortality in individuals with type 1 diabetes from the FinnDiane study associated each level of albuminuria and end-stage kidney disease (ESKD). Adjusted hazard ratios with 95% CIs are standardized against individuals with UAE in the normoalbuminuric range (arbitrary value of 1.0). Adjusted SMRs with 95% CIs are provided standardized against the age- and sex-matched Finnish general population (arbitrary value of 1.0).

FIG. 3.

Relationship of estimated GFR to the hazard ratio for mortality in individuals with type 1 diabetes without end-stage kidney disease from the total FinnDiane cohort (A) and in individuals with normoalbuminuria (B), microalbuminuria (C), and macroalbuminuria (D). Dotted line shows point estimate for cubic regression spline adjusted for other predictive variables. Gray area denotes 95% CI.

FIG. 4.

Relationship of A1C to the hazard ratio for mortality in individuals with type 1 diabetes without end-stage kidney disease. Dotted line shows point estimate for the cubic regression spline adjusted for other predictive variables. Gray area denotes 95% CI.