Article Risk Prediction for Early CKD in Type 2 Diabetes

Background and objectivesQuantitative 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. Design, setting, participants, & measurements 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 normoor microalbuminuria at baseline were included. Incidence or progression of CKD after 5.5 years was defined as new microor macroalbuminuria, doubling of creatinine, or ESRD. The competing risk of death was considered as an additional outcome state in the multinomial logistic models. ResultsOf 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 R2 value of 10.6%.Albuminuria, modeled to depict the difference between baseline urinary albumin/creatinine ratio and the threshold for microor 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 R2 value only to 0.69 and 12.1%, respectively. Explained variation was largely driven by renal and not clinical predictors. Conclusions 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. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.10321014 Introduction CKD is a significant health care problem: 13% of the adult population of the United States have reduced kidney function or albuminuria (1). Especially, in people with diabetes, predicting the course of CKD is important because decline in kidney function and response to therapy vary considerably between individuals (2). Because unselective screening for kidney disease is not cost-effective (3,4), stratification of people at risk for CKD or progression of CKD is urgently needed in analogy to the highly successful risk calculators in the area of cardiovascular medicine (5). In people with diabetes, for example, screening for established CKD with measurements of albuminuria and eGFR has been shown to be cost-effective, with estimated costs of $18,650 (2009) per quality-adjusted life-year gained (6). Because primary prevention strategies are likely to be most cost-effective (6), it is also desirable to predict incident CKD in people with diabetes before microalbuminuria develops and CKD progression in those with microalbuminuria. However, no externally validated risk calculator exists for prediction of incidence and progression of early CKD in people with diabetes. Therefore, we used data of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) to assess the risk of incidence or progression of CKD after 5.5 years for people aged $55 years with diabetes and normoor microalbuminuria (7–9). The competing risk of death was considered as an additional outcome state by using multinomial logistic regression. The Outcome Reduction with Initial Glargine Intervention (ORIGIN) cohort was used for external validation, and the relative importance of predictors was quantified (10–13). Materials and Methods Study Population Development Cohort. ONTARGET included individuals aged $55 years with vascular disease or diabetes with end-organ damage. Exclusion criteria *Population Health