Inside ckd: projecting the population level clinical burden of chronic kidney disease according to urine albumin-to-creatinine ratio categories

Abstract Background and Aims Chronic kidney disease (CKD) and its associated complications constitute a major challenge for healthcare systems worldwide. Albuminuria, measured as albumin-to-creatinine ratio (uACR), is a critical marker of glomerular injury and endothelial dysfunction. Elevated uACR is an independent predictor of CKD progression and cardio-renal mortality [1,2]. However, there is a paucity of data translating the burden of CKD at the population level according to uACR categories, in order to promote evidence-based policies. This study aims to assess the future epidemiological and financial burden of CKD using the Inside CKD microsimulation [3]. Specifically, we report CKD population level projections for cardio-renal complications, progression to end stage kidney disease (ESKD), and death due to any cause according to uACR categories. Method The Inside CKD microsimulation was used to simulate virtual individuals from 28 countries and regions. Individuals were assigned baseline characteristics such as age or sex based on national statistics, and estimated glomerular filtration rate (eGFR), uACR, CKD stage, and cardio-renal complications based on data from national health surveys or epidemiological studies. The following cardio-renal complications were projected between 2022 and 2027 according to uACR categories (normo-, micro-, macro-albuminuria): myocardial infarction (MI), stroke, heart failure (HF), CKD transition from stage 3 to 4 and from 4 to 5 (defined as a change in either eGFR or uACR category), and death due to any cause. Results Projected estimates for the total CKD population (all stages) with macro-albuminuria varied by country and region for 2023 (mean = 9.8%, range = 1.6% – 40.2%). The lowest percentages of macro-albuminuria (< 5%) were in Romania, Belgium, and the UK, compared to the highest (≥ 27%) in Brazil, Philippines and Mexico. Macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per person basis, but according to these estimates only a small proportion of the population have macro-albuminuria. Hence, the predominant CKD population with normo- or micro-albuminuria would be expected to account for most of the clinical burden. Accordingly, most of the cardio-renal incident events projected to occur by 2027 will be in the population with normo- or micro-albuminuria in all countries and regions (Figure 1): MI (97.9%), stroke (96.5%), HF (98.0%), the transition from CKD stage 3 to 4 (94.9%) and from stage 4 to 5 (97.5%), and death due to any cause (95.6%) (percentages represent mean and included the combined normo- and micro-albuminuria populations). Conclusion Although, macro-albuminuria is associated with a higher relative risk of cardio-renal outcomes on a per patient basis, the total CKD population should be considered with regards to the clinical burden in absolute terms. The Inside CKD microsimulation supports early intervention in the total CKD population, including individuals with normo- or micro-albuminuria, to reduce cardio-renal outcomes, delay progression to ESKD, and therefore the requirement for costly interventions, including heart related hospitalisations, transplantation and dialysis.