Diabetes mellitus as a cause of end-stage renal disease in Europe: signs of improvement

The ERA-EDTA Registry is an international collaboration collecting data on renal replacement therapy (RRT) in Europe and countries bordering the Mediterranean Sea via national and international registries. The data are used for focused scientific studies on specific questions and for epidemiological surveillance of the state of RRT in Europe, which is evaluated annually and presented in the traditional ERA-EDTA Registry Reports. In this issue of the Clinical Kidney Journal, Kramer et al. [1] provide a summary of the 2013 ERA-EDTA Registry Annual Report. At present, the ERA-EDTA Registry covers 49 registries in 34 countries. Almost two-thirds of these registries offer individual patient data. The summary focused on diabetes mellitus (DM) as a cause of end-stage renal disease (ESRD) requiring RRT.

Diabetes is an important health concern. The estimated prevalence rate of diabetes in Europe was 8.5% in 2013 and is projected to increase to 10.3% in 2035 [2] (Figure 1). It is one of the main underlying causes of death in adults, accounting for ∼10% of all deaths in Europe [3]. Furthermore, persons who have diabetes in addition to chronic kidney disease have an ∼50% higher risk of ESRD and death than those at a similar level of estimated glomerular filtration rate [4]. Therefore, it is an important contributor to RRT in Europe. In total, 477 186 persons in Europe were receiving RRT in 2013. This amounts to an overall prevalence rate of 738 patients per million population in Europe and the Mediterranean, and 17% of these patients had DM as the primary cause of kidney disease. The average incidence rate of RRT in 2013 was 122 persons per million population who started RRT in 2013 in the ERA-EDTA Registry area. About 24% of the incident RRT cases had DM as the primary cause of their kidney disease. One immediately notes the marked difference between the proportion of incident RRT cases due to DM and the proportion of prevalent RRT patients with DM. The authors report a markedly poorer 5-year survival rate on RRT of 50.6% for patients who had DM as the primary kidney disease when compared with the overall 5-year survival rate on RRT of 60.9%. Fortunately, evaluation of more recent short-term survival sends a more uplifting message: the overall 2-year survival rate on RRT has improved from 81.4% between 2004 and 2008 to 82.7% between 2007 and 2011. This improved survival rate was even more pronounced in patients who suffered from ESRD requiring RRT due to diabetes: from 77.3% between 2004 and 2008 to 79.4% between 2007 and 2011.

Fig. 1.

Trends in diabetes prevalence and forecasted prevalence of diabetes in Europe. The black line represents the observed prevalence of diabetes over time. The dotted, grey line is the forecasted prevalence. Data from Shaw et al. [5], Danaei et al. [6], Whiting et al. [7] and Guariguata et al. [2].

Even more remarkably were the trends in incidence of RRT due to DM over the past decade. Despite a decreasing incidence of DM, its prevalence rate has steadily increased over the past few decades and is projected to increase even further in the two decades to come [2, 6]. Given the substantial proportion of patients with DM who develop chronic kidney disease and ultimately ESRD, one would expect the incidence of RRT as a consequence of DM to increase as well. However, Kramer et al. [1] show that the incidence of RRT has remained stable over the past 10 years, even trending towards a slight decrease in recent years (see Figure 3 of their paper). They made a similar observation on data from the United States Renal Data System (USRDS). These results mean that the prevention of chronic kidney disease secondary to DM has improved, at least for Western countries.

Still, the incidence of RRT secondary to DM was five times higher in the USA compared with Europe, whereas that of RRT due to other causes of kidney disease was two times higher. This may indicate that the progression of CKD to ESRD due to DM is far greater in the USA compared with Europe. One may speculate about underlying causes, which could include (i) differences in the management of ESRD, (ii) differences in genetic background, particularly in African Americans and (iii) differences in the prevalence of risk factors for progressive kidney damage. A study by van de Luijtgaarden et al. [8] indicated that nephrologists in high RRT incidence countries were more likely to offer RRT for ESRD, even when they expect gains in quality of life and survival to be modest [8]. Furthermore, the EVEREST study indicated that the incidence of RRT was higher in high-income countries with a larger proportion of private for-profit dialysis facilities [9]. This may indicate that, in general, physicians in the USA may be more willing to start RRT in older patients with more comorbidities than those in Europe. It highlights an important limitation of the ERA-EDTA date in general: it captures only treated cases of RRT and not cases of ESRD who are treated conservatively or die prior to the initiation of RRT. An analysis of USRDS data indicates that even in white Americans, the incidence of RRT is markedly higher compared with Europeans [10]. Therefore, differences in genetic background do not fully explain the differences in RRT risk between Europe and the USA.

Elevated blood pressure is an important culprit in the progression of diabetic nephropathy. Several trials indicate that aggressive treatment of blood pressure in diabetic patients results in marked improvement in both overall and renal survival. Perhaps surprisingly, World Health Organization reports indicate that the prevalence of elevated blood pressure is substantially higher in Europe than in the USA [11]. Clearly, differences in blood pressure control do not explain the difference in RRT risk between Europe and the USA. Moreover, given the comparatively high frequency of elevated blood pressure in Europe, there may even be room for improvement in the prevention of ESRD.

If blood pressure does not explain the difference in RRT rate between the USA and Europe, perhaps other underlying causes of ESRD are more important. Elevated blood pressure may be the cause, but also a consequence of vascular damage. Obesity, poor glycaemic control and hyperlipidaemia all contribute to vascular damage. Experimental evidence also suggests that low-grade inflammation—a consequence of adiposity [12, 13], hyperglycaemia [14] and hyperlipidaemia [15]—have a direct deleterious effect on the kidney as well. These potential underlying causes of vascular and renal damage are more prevalent in the USA compared with Europe. A formal comparison between the USA and Europe may shed light on the determinants for the marked difference in RRT risk between the two regions, which may highlight possible differences at a population level rather than the individual patient level [16]. In turn, such data may help both physicians and public health workers in the USA and Europe to improve prevention of ESRD secondary to DM.

All in all, the data presented by Kramer et al. [1] give us reason to be optimistic, and even though there may be some room for improvement, secondary prevention of kidney damage in diabetic patients seems to be working, thus curbing the expected increase in ESRD due to DM. However, despite stabilizing DM incidence in recent years [17], the peak in DM prevalence is still to come as persons with DM live longer than before. Continued effort is needed to address the underlying causes of diabetes and diabetic nephropathy at a population level. We seem to have won the first battle in the fight against ESRD due to diabetes, but the war is far from over.