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Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3‐year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second‐line glucose‐lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m2), baseline prevalence estimates for stage 0‐1, 2, 3 and 4‐5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow‐up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9‐3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m2 over follow‐up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second‐line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.


Funding information
The DISCOVER study programme is funded by AstraZeneca. defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m 2 ), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/ 1.73 m 2 over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.

| INTRODUCTION
Diabetes is the most common cause of chronic kidney disease (CKD), and the prevalence of CKD among patients with diabetes is reported to be up to 40%. [1][2][3][4][5] However, data for many countries are scarce. 1 DISCOVER is a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucoselowering therapy. 6 Here, we report the baseline prevalence of CKD, and changes in CKD severity during follow-up.

| METHODS
The DISCOVER study methodology has been reported previously (ClinicalTrials.gov: NCT02226822/NCT02322762). 6,7 Study sites in 38 countries were selected to be as representative as possible of T2D management in each country, 8 and consecutive adult patients with T2D were enrolled at each site if they were initiating secondline glucose-lowering therapy (add-on or switch) after first-line oral therapy. Initiation of second-line therapy was chosen for study baseline because of the diversification of guideline-recommended medications available at this point in the treatment pathway. 9,10 Exclusion criteria included type 1 diabetes, first-line treatment with an injectable agent or with natural medicines alone, and renal transplantation or dialysis (Table S1). Data were collected according to Albuminuria and urine albumin-to-creatinine ratio (UACR) data were not assessed owing to rates of missing data of 80.0% or higher (either not recorded or test not performed). Disease change over follow-up was assessed in patients who had serum creatinine measurements at baseline and at least one follow-up time point. Progression and regression were defined as an increase or decrease, respectively, of at least one CKD stage from baseline to the last available measurement.

| RESULTS
In total, 14 041 patients were eligible for the analysis, of whom 7843 (55.9%) had a baseline serum creatinine measurement ( Table 1)  . Patients whose disease progressed had higher levels of concomitant medication use than patients whose disease regressed or remained stable, but other characteristics were similar (Table S3).

| DISCUSSION
We observed a baseline prevalence of 48.5% for stage 2 or greater CKD among patients with T2D initiating second-line therapy, and a prevalence of 10.8% for stage 3 or greater CKD. This is in line with or higher than estimates reported in previous studies. For example, in the United States the prevalence of stage 1-5 CKD among patients with diabetes is reported to be 36.0%, while in the UK the prevalence of microalbuminuria 10 years after the diagnosis of T2D is 24.9%. 4,5 The high prevalence of CKD may be explained by the quality of care in the countries included relative to those assessed in previous studies. Our results may also reflect some degree of selection bias, as the measurement of serum creatinine levels may have been more probable in patients with or at risk of CKD. In line with this, comparison of patient characteristics revealed a higher prevalence of prior T A B L E 1 Regional variation in serum creatinine measurement, baseline chronic kidney disease (CKD) prevalence by stage, and CKD progression during follow-up   F I G U R E 1 Changes in estimated glomerular filtration rate (eGFR) and use of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), A, overall, and B, according to baseline chronic kidney disease (CKD) severity. Whiskers represent 95% CIs of the study, and indicate suboptimal disease management. Regular monitoring of patients would help to identify and manage CKD at an early stage.