Trends in the incidence of kidney replacement therapy: comparisons of ERA, USRDS and Japan registries

The number of patients requiring kidney replacement therapy (KRT) is increasing worldwide [1]. The objectives of global chronic kidney disease (CKD) countermeasures are to prevent the deterioration of renal function in CKD patients and reduce not only the physical burden associated with end-stage kidney disease (ESKD) and cardiovascular disease (CVD), but also the social burden caused by an increase in the number of patients receiving KRT. Therefore, the early detection of CKD as well as the development of and investigations on effective treatment methods have been promoted. The steady implementation of CKD countermeasures is expected to reduce the number of patients with ESKD in the future. Specifically, the ability to show annual trends and decreases in the number of new ESKD patients on a national and regional basis will be important for demonstrating the achievement of important goals in the fight against CKD. Alternatively, differences in the incidence of ESKD may be assessed based on annual transitions in the number of patients at each stage of CKD (G1 to G5), particularly CKD G5 patients. Although previous studies in some countries accurately showed the number of CKD G5 patients [2], difficulties are associated with correctly assessing these numbers in most countries and regions [3]. While international comparisons based on the exact incidence of ESKD would be ideal, the incidence of KRT is regarded as the incidence of ESKD instead. However, the incidence and prevalence of KRT markedly differ from those of CKD in each country and region. In comparisons of the incidence of KRT among the European Renal Association (ERA), United States Renal Data System (USRDS) and Japan registries, which included more than 20 years of KRT registration, the incidence of KRT per million population in 2019 was 411.7 in the USA, 327.5 in Japan and >50% lower at 145 in the ERA. These findings were attributed to differences in the incidence of ESKD among countries and races, life expectancy due to diseases other than ESKD, coverage by national medical insurance systems for KRT and the acceptance rate of KRT. Among these, social factors had a marked effect on the incidence of ESKD in most countries and regions. Serial observations of trends in the incidence of KRT in the USA, Japan and Europe are considered to reflect secular changes in the incidence of ESKD because of the long-term stability of social factors in these countries. In Europe, the number of new KRT patients increased at an annual rate of 4.8% (95% CI 4.5% to 5.0%) between 1990 and 1999, but gradually declined after 2000, with a marked reduction of –2.2% in new patients between 2008 and 2011 (95% CI –4.2% to –0.2%) [4]. The implementation of CKD countermeasures was expected to decrease the number of new KRT patients. In this month of NDT, follow-ups on this report by further trends in new KRT patients in Europe since 2008, prevalence and survival of patients on KRT across Europe were reported [5]. Huijben et al. showed that the incidence of KRT in eight European countries decreased between 2008 and 2011 [–1.48% (–3.15% to 0.21%)], but significantly increased between 2011 and 2017 [1.01% (0.43% to 1.60%)] [5]. Therefore, a transient decrease was noted in the incidence of KRT. Prior to this decrease, the early initiation of KRT before the onset of uremic symptoms was considered to be a survival advantage, and, thus, the early initiation of KRT was attempted [4]. However, negative findings were obtained in clinical studies on the symptom-free early initiation of dialysis [6], which suggested that the clinical significance of the introduction of early dialysis had diminished. Therefore, the timing of the initiation of dialysis was delayed until the development of uremic symptoms [4], which was considered to be one of the factors contributing to the decrease observed in the incidence of KRT between 2008 and 2011 in Europe. Similar changes were reported in the USA between 2010 and 2012 and in Japan between 2011 and 2013. This difference appeared to have been influenced by the timing of the publication of guidelines on recommendations for the initiation of dialysis in each country [7]. According to trends in the incidence of KRT in the last 20 years, an increase was detected in each registry (Fig. 1A). Trends in the incidence of KRT in ERA, USRDS and Japan registries every 5 years for the past 20 years. Variations in the incidence of KRT were compared in long-term continuous KRT registries [2019 prevalence in ERA (n = 607 320), USRDS (n = 809 103) and Japan (n = 344 640; dialysis patients only)]. (A) Five-year trends in the incidence of KRT per million population. Each registry has increased over time. (B) Five-year trends in the average age of patients at the initiation of KRT. (C) Five-year trends in the male-to-female ratio of patients initiating KRT. (D) Five-year trends in the primary renal disease of patients initiating KRT. DM: diabetes mellitus in ERA, diabetes in USRDS and diabetic nephropathy in Japan; HT: hypertension in ERA and USRDS, nephrosclerosis in Japan; GN: glomerulonephritis/sclerosis in ERA, glomerulonephritis in USRDS and chronic glomerulonephritis in Japan; PKD: Polycystic kidneys, adult type in ERA, cystic kidney in USRDS polycystic kidney in Japan. Data sources: ERA: https://www.era-online.org/en/registry/, USA: USRDS https://adr.usrds.org/2021/end-stage-renal-disease, Japan: https://docs.jsdt.or.jp/overview/index.html and http://www.asas.or.jp/jst/. In recent years, the elderly population and number of middle-aged and elderly patients with lifestyle-related diseases, such as diabetes, hypertension and dyslipidemia, have been increasing, with a longer life expectancy due to advances in the treatment of CVD and stroke being the main reason for the older age at which ESKD develops. Furthermore, recent changes in Japan include the establishment of an early detection system for glomerulonephritis and advances in its treatment, which have led to a decrease in the incidence of KRT due to glomerulonephritis as well as an increase in the age of patients at the time of the progression of glomerulonephritis to ESKD [8]. Furthermore, the average age of patients at the initiation of dialysis has been increasing more rapidly over time in Japan than in Europe and the USA, rising to 70.4 years by 2019, and this has largely been attributed to a decline in the younger Japanese population and longer life expectancy. Japanese data include dialysis patients, but not preemptive kidney transplant (PEKT) patients; there were 40 885 dialysis inductions and 437 PEKT in 2019 and 38 327 dialysis inductions and 207 PEKT in 2014, which may be another reason for the rapid increase in the average age of patients at the initiation of dialysis in Japan (Fig. 1B). The male-to-female ratio of the incidence of KRT has also been increasing. Trends in the incidence of KRT in Japan by sex and age revealed an increase in men aged 85 years and older, but not in men aged 75–84 years or women aged 85 years and older, and decreases in other age groups [9]. In Europe, an increase was noted in the incidence of KRT in males aged 65 years and older only [5]. Increases in the incidence of KRT in men, particularly those aged 65 and older, and diabetic patients as well as in ESKD with diabetic nephropathy or diabetes were also common in many countries. Changes over time in the male-to-female ratio of patients receiving KRT (Fig. 1C) showed a slower increase in males in Europe than in the USA and Japan. The slow increase observed in Europe may be attributed to the diversity of the participating countries in ERA. Although a sex difference was not observed in the incidence of lifestyle-related diseases, such as hypertension, diabetes and dyslipidemia, in most countries, various hypotheses have been proposed for the reason for this sex difference in the incidence of KRT over time. Previous studies revealed a sex difference in the rate of the deterioration of renal function with conservative chronic renal failure, the potential of estrogen to act as a renal protector, a sex difference in the acceptance rate of KRT [10] and a decrease in the number of ESKD patients with lupus nephritis due to advances in its treatment, which has been more prevalent in women. Furthermore, differences in the classification and diagnosis of primary renal disease (PRD) need to be considered when comparing registries. For example, the ERA registry defines GN as glomerulonephritis + sclerosis, while nephrosclerosis is regarded as hypertensive nephropathy in Japan [5]. Diabetic nephropathy was the most common PRD in the ERA, USRDS and Japan registries; however, an incremental trend was only observed in the USA. Furthermore, diabetic nephropathy and diabetes-related chronic renal failure were not clearly distinguished from each other in the KRT registry, and this difference in classification may be reflected in the different percentages of diabetes in each registry. The recent decrease in KRT due to diabetic nephropathy and increase in patients with unknown diseases in the ERA and Japan registries may be attributed to increases in hypertensive nephropathy complicated by diabetes and other cases that are difficult to classify as a single disease. The percentage of patients receiving KRT due to ADPKD has remained unchanged in each region over time (Fig. 1D). In international comparisons of ESKD, we need to investigate variations in CKD stages over time, clarify the number of new cases of ESKD and unify the classification of ESKD. The establishment of uniform standards is desired for comparative studies, which may only be conducted when the same standards are applied, such as the unification of PRD classifications. This work was supported by JSPS KAKENHI Grant Number 21K08220. None declared. I declare that the results presented in this paper have not been published previously in whole or part, except in abstract format.