Risk Prediction for Early CKD in Type 2 Diabetes

• Published in: Clinical journal of the American Society of Nephrology Vol. 10; no. 8; pp. 1371 - 1379
• Main Authors: Dunkler, Daniela, Gao, Peggy, Lee, Shun Fu, Heinze, Georg, Clase, Catherine M, Tobe, Sheldon, Teo, Koon K, Gerstein, Hertzel, Mann, Johannes F E, Oberbauer, Rainer
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 07-08-2015
• Subjects: Aged; Albuminuria - diagnosis; Albuminuria - epidemiology; Albuminuria - physiopathology; Biomarkers - blood; Creatinine - blood; Decision Support Techniques; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - mortality; Diabetic Nephropathies - blood; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - epidemiology; Diabetic Nephropathies - mortality; Diabetic Nephropathies - physiopathology; Disease Progression; Female; Glomerular Filtration Rate; Humans; Incidence; Kidney - physiopathology; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Original; Predictive Value of Tests; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - mortality; Renal Insufficiency, Chronic - physiopathology; Reproducibility of Results; Risk Assessment; Risk Factors; Time Factors; glomerular filtration rate; proteinuria; diabetes mellitus
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/cjn.10321014

Quantitative data for prediction of incidence and progression of early CKD are scarce in individuals with type 2 diabetes. Therefore, two risk prediction models were developed for incidence and progression of CKD after 5.5 years and the relative effect of predictors were ascertained.
Baseline and prospective follow-up data of two randomized clinical trials, ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Outcome Reduction with Initial Glargine Intervention (ORIGIN), were used as development and independent validation cohorts, respectively. Individuals aged ≥55 years with type 2 diabetes and normo- or microalbuminuria at baseline were included. Incidence or progression of CKD after 5.5 years was defined as new micro- or macroalbuminuria, doubling of creatinine, or ESRD. The competing risk of death was considered as an additional outcome state in the multinomial logistic models.
Of the 6766 ONTARGET participants with diabetes, 1079 (15.9%) experienced incidence or progression of CKD, and 1032 (15.3%) died. The well calibrated, parsimonious laboratory prediction model incorporating only baseline albuminuria, eGFR, sex, and age exhibited an externally validated c-statistic of 0.68 and an R(2) value of 10.6%. Albuminuria, modeled to depict the difference between baseline urinary albumin/creatinine ratio and the threshold for micro- or macroalbuminuria, was mostly responsible for the predictive performance. Inclusion of clinical predictors, such as glucose control, diabetes duration, number of prescribed antihypertensive drugs, previous vascular events, or vascular comorbidities, increased the externally validated c-statistic and R(2) value only to 0.69 and 12.1%, respectively. Explained variation was largely driven by renal and not clinical predictors.
Albuminuria and eGFR were the most important factors to predict onset and progression of early CKD in individuals with type 2 diabetes. However, their predictive ability is modest. Inclusion of demographic, clinical, and other laboratory predictors barely improved predictive performance.