Abstract Background and Aims Chronic kidney disease (CKD) is one of the fastest growing global causes of death and the number of persons on kidney replacement therapy (KRT) is increasing. A critical assessment of current clinical practice in different regions may identify best clinical practice and provide a benchmark to improve outcomes. Given the current long-life expectancy in Spain and its high proportion of elderly population, analysis of Spanish data may provide insight of interest for the future for other European countries. Catalonia (Cat) and Madrid (Mad) are among the three most populated Spanish Autonomous Communities and have similar life expectancy, gross domestic product (GDP) and GDP per capita, accounting for 30% of Spain's population and 38% of GDP. The aim was to set the basis for benchmarking in CKD care and KRT initiation and care by comparing the evolving prevalence of KRT in Cat and Mad. Method We compared KRT prevalence in Cat and Mad over the past years using data from European Renal Association (ERA) Registry annual reports and Spanish Instituto Nacional de Estadística's (INE) census. Results From 2012 to 2021, the adjusted prevalence of KRT per million population (pmp) increased by 275.8 (1221 to 1479, 22.6% increase) in Cat and by 134.8 (1046 to 1118, 12.9% increase) in Mad. The difference between Cat and Mad increased from 175 to 316 pmp (60% increase), resulting in a 26.8% higher KRT prevalence in Cat than in Mad in 2021 (up from 16.7% higher in 2012) (Fig. 1A). During the same period, the median age of prevalent KRT patients increased from 63.2 to 65.4 years (yrs) (2.2 yrs, 3.5%) in Cat and from 62.2 to 63.8 years (1.6 yrs, 2.6%) in Mad. In 2021, median age for prevalent patients on KRT was 1.6 yrs older in Cat (65.4 (53.9, 75.3)) than in Mad (63.8 (52.6, 74.1)), this difference being of 2.5 yrs in women (Cat 65.5 (53.6, 75.7), Mad (63 (51, 73.8), difference) and 1.1 yrs in men (Cat 65.3 (53.9, 75); Mad 64.2 (53.4, 74.3)). In subgroup analysis by age and sex, prevalence of KRT per million age-related population (pmarp) in 2021 was always higher in Cat than in Mad, except for women aged 20-44 yrs (363.7 in Cat, 370.5 in Mad, Cat/Mad ratio 0.98), and the largest gap was observed for women <19 yrs (Cat 77.4, Mad 41.5, Cat/Mad ratio 1.86). The Cat-Mad ratio increased with age in women >45 yrs, but not in men (Fig. 1B) The contribution of diabetes to KRT prevalence remained stable or increased slightly in both Cat (13.9-15.5%) and Mad (17.4-17.7%) between 2012 and 2021. In 2021 for most causes of KRT the prevalence adjusted for age and sex was higher in Cat, except for hypertension and miscellaneous. The largest differences were observed for unknown cause (most common cause in Cat: Cat 330.8, Mad 85.5, difference 245.3 pmp), miscellaneous (most common cause in Mad: Cat 165.9, Mad 271.5, difference −105.6 pmp), and missing (Cat 53.8, Mad 0, difference 53.8 pmp) (Fig. 1C). Prevalence of kidney transplantation in 2021 was higher in Cat than Mad (60.0% vs 54.9%), while prevalence of hemodialysis and peritoneal dialysis was higher in Mad (39.6% and 5.5%, respectively) than in Cat (36.2% and 3.9%) (Fig. 1D). Conclusion In conclusion, a stark difference in prevalence trends and in current KRT was observed for two Autonomous Communities within the same country which are broadly comparable in terms of population, life expectancy and GDP. An in-depth analysis of the drivers of these differences may bring insight into best practices for CKD prevention, treatment to slow CKD progression, timing and criteria for initiation of KRT and standard of care for KRT.