#1185 Cardiovascular, renal and mortality risk by the KDIGO risk classification: the first observational study in Japan
Authors: Maruyama Shoichi , Akiyama Hiroki , Ozaki Asuka , Tanaka Tetsuhiro 
Published: May 2024

Abstract

Background and Aims
The prevalence of chronic kidney disease (CKD) has been increasing, affecting 850 million people worldwide and 13 million individuals in Japan. CKD is a risk factor for cardiovascular complications including heart failure, and dialysis. KDIGO risk classification is widely used for the management of people with CKD in Japan; however, risk of clinical outcomes by the KDIGO classification in Japanese population is unclear. The aim of this study is to describe the risk of major adverse cardiovascular event (MACE) and renal outcomes according to the KDIGO classification in Japanese clinical practice.

Method
This study was a cohort study using data collated from the RWD database which includes electronic medical records and claims data from approximately 200 medical institutions across Japan since 2000. Subjects aged ≥18 years with two or more consecutive results of eGFR &lt;90 mL/min/1.73 m2 at least 90 days apart within a 360-day period were included, and those received renal replacement therapy (RRT; dialysis or renal transplantation) before the index date was excluded. The index date was defined as the date of the second eGFR measurement &lt;90 mL/min/1.73 m2 between January 2004 and December 2020. Patients were categorized into KDIGO classification G2-G5 based on their eGFR values and A1-A3 based on urine protein test (quantitative test and urine dipstick) results and into `no urine protein data` if no urine protein test was available.
The primary endpoint was MACE that was defined as a composite of myocardial infarction, stroke, heart failure hospitalization, and in-hospital death. The secondary endpoint was renal outcomes defined as a composite of RRT, eGFR decline &gt;50%, eGFR &lt;15 mL/min/1.73 m2, diagnosis of CKD stage 5, and in-hospital death, and was analyzed in the group excluding patients with eGFR &lt;15 mL/min/1.73 m2 or with diagnosis of stage 5 CKD on or before the index date. The risk of MACE and renal outcomes were evaluated using the cox proportional hazards model with G2A1 as a reference. Sensitivity analyses were performed for the population excluding those without urine protein data and for the population with quantitative urine protein test results.

Results
This study included 543,606 patients who met the criteria. Mean age was 61.6 ± 15.3 years, and 50.1% was male. Of those, 222,246 (40.9%) had no urine protein data. Tables 1 and 2 show hazard ratio (HR) for MACE and renal outcomes, respectively. HR (95% confidence interval) for MACE was 1.17 (1.12-1.21) in G2A2 and 1.16 (1.12-1.20) in G3aA1, showing significantly increased risk in early stages of CKD, and continued to increase as disease advances to 2.83 (2.54-3.15) in G5A3. HR for renal outcomes was similarly significantly increased in early stages of CKD, and further increased to 19.96 (18.62-21.40) in G4A3. Results of two sensitivity analyses, excluding subjects with no urine protein data (n = 321,360, 59.1% of overall population) shown in Table 3 and 4, and excluding patients with no quantitative data (n = 36,615, 6.7% of overall population) showed similar trends, supporting the robustness of primary findings.

Conclusion
This study is the first to demonstrate the applicability of the KDIGO risk classification in assessing the risk of cardiovascular events, including heart failure, and renal outcomes in Japan. Risk of events was increased from early stages of CKD (G3aA1 and G2A2), suggesting the importance of early diagnosis and therapeutic intervention through appropriate testing. These findings may contribute to better management of people with CKD.