Prevalence and related risk factors of chronic kidney disease among adults in Luxembourg: evidence from the observation of cardiovascular risk factors (ORISCAV-LUX) study

During the last decade, there has been a rising interest in the epidemiology of chronic kidney disease (CKD), which is now recognized as an important public health problem worldwide [1]. Patients with CKD are at high risk for progression to end stage renal disease (ESRD); a condition often requiring costly renal replacement therapy in the form of dialysis or transplantation. Although over 2 million people now require chronic renal replacement therapy worldwide [2, 3], only a minority of patients who are at risk for developing ESRD are under medical attention [4]. Moreover, CKD is associated with eight- to ten-fold increased risk of cardiovascular disease (CVD) mortality [5, 6]. Other complications include acute kidney injury, increased risk of infection, cognitive decline, anaemia, mineral and bone disorders and fractures [7].

The economic impact of CKD is enormous, whether related to direct healthcare cost or to indirect productivity lost with profound consequences on the quality of life of the individual, his family and society [3]. Recently, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) ranked low glomerular filtration rate (GFR) as the 12th leading risk factor for death at the global level, and the 14th risk factor for Disability-Adjusted Life-Years (DALYs) among 79 risk factors in 2013 [8]. In the past decade, attention has moved from treating only advanced stages of CKD toward prevention at earlier stages of CKD [4]. However, due to the asymptomatic nature of slowly progressing renal damage, CKD is frequently undetected until the very late stages, with few opportunities for prevention. Therefore, focusing efforts on early detection and treatment of CKD can prevent or delay progress to kidney failure or other adverse outcomes [9].

Low GFR has been identified among the top 10 leading cause of DALYs for both sexes in Luxembourg [10], where cardiovascular mortality accounts for about one-third of all deaths [11], and associated cardio metabolic pathologies, such as diabetes, hypertension, lipid disorders and obesity are demonstrably high [12, 13]. The objectives of this study were to provide baseline evidence on the prevalence of CKD among the general population in Luxembourg, to assess the different stages of CKD and identify potential socio-economic, clinical and behavioural correlates. Accurate assessment of CKD stages among the general population may provide important evidence-based information for policy makers and healthcare professionals regarding strategies for CKD prevention and healthcare planning.

CKD has been recognized as a worldwide public health problem due to rising prevalence, association with CVD mortality, poor outcomes, and dramatic complications which imply high costs and important burden on health care systems [19]. Renal epidemiology has blossomed in recent years, following several publications on renal impairment diagnosis and uniform clinical practice guidelines. This is the first nationwide study to describe the epidemiology of CKD in Luxembourg, based on a standardized definition and staging of renal impairment, as suggested by the internationally accepted KDOQI guidelines [19, 22].

Our findings indicate that more than 6% of the general population in Luxembourg (representing >18,000 adults nationally) suffered from one of the 5 stages of renal impairment. Moreover, 0.7% (representing >2000 people) had severe macroalbuminuria (>300 mg/g Cr), and 0.1% had kidney failure. Normal individuals usually excrete very small amounts of protein in the urine. Persistently increased protein excretion is usually a sensitive marker of kidney damage. These findings flag a neglected public health issue in Luxembourg, which warrants national attention and further investigations.

These prevalence estimates were comparable to data from Lausanne city in Switzerland, where one in 10 adults suffers from CKD, using similar diagnostic criteria [26]. Recent CKD Burden Consortium data suggests a substantial variation (from 3.3% to 17.3%) in CKD prevalence across Europe [27]. Based on earlier studies, a South-North gradient has been observed in CKD prevalence estimates, being higher in northeastern Italy (13.2%) [28] and Galician population in Spain (12.7%) [29] compared with Iceland (age-adjusted prevalence of low eGFR for adults, aged 35–80 years, was 4.7 and 11.6% for men and women, respectively) [30]. In the USA, 25 million people (about 12%) are estimated to have CKD, whereas only <0.2% (<500,000) have kidney failure treated by dialysis or transplantation [1, 31]. Similar prevalence estimates have been reported in Australia [32], and some reports note an increasing prevalence over time [33, 34]. Although our national CKD estimates are lower than the worldwide range (8–16%), [7] their public health burden is worsening with escalating CVD mortality and comorbidities, presenting substantial medical expenses.

Thus far, studies on CKD prevalence have been hampered by selection bias, or inappropriate detection criteria to define CKD stages [35]. Direct international comparisons is difficult due to important methodological differences regarding the setting of the target population, study design, as well as to the variety of CKD definitions used across different studies.

There are a number of potential factors that may have contributed to the relatively high prevalence of CKD among adults in Luxembourg. Consistent with previous reports [26], an elevated prevalence of CKD was observed in hypertensive (70.3%), diabetic (23.1%) and obese (44%) participants in the ORISCAV-LUX study. These conditions are highly prevalent in the Luxembourg population, as supported by our previous findings from ORISCAV-LUX study population [12]. The likelihood for CKD was significantly and independently increased by 3-fold and 4-fold in the presence of hypertension and diabetes, respectively. In addition, elevated serum triglycerides was substantially associated with higher odds for CKD. Evidence suggests that hypertension and diabetes are two major causes of kidney disease [36, 37]. As a complication, high BP may also develop early during the course of CKD and is associated with adverse outcomes, in particular, faster loss of kidney function and development of CVD [19]. In addition, the risk of CVD, retinopathy, and other diabetic complications is higher in patients with diabetic kidney disease than in diabetic patients without kidney disease [19]. Recently, accumulated evidence indicates that the adverse outcomes of CKD can be prevented or delayed through therapeutic interventions during earlier stages, including blood glucose control in diabetic subjects, regular BP control, treatment with angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, and dietary protein restriction. Because of the well-known interactions between CVD, hypertension, diabetes, and CKD, these findings have important clinical and public-health implications, in targeting these “high-risk” population subgroup of the population, who may benefit most from treatment to reduce progression and delay the onset of ESRD and cardiovascular complications [3, 38].

Increased physical activity was independently associated with lower odd for CKD. This association remained significant after further adjustment for demographic, socio-economic, and other lifestyle factors. From a public health standpoint, these findings may be interesting. Only a few population-based studies have reported this relationship [39, 40]; further prospective studies are needed to replicate this finding.

This is the first evidence-based report on the epidemiology of CKD in Luxembourg, highlighting that early preventive measures are needed to detect chronic kidney impairment and to reduce the incidence and mortality arising from the associated comorbidities. Given the burden of this public health problem [10], such data should guide national authorities and contribute to increase the awareness of scientific societies regarding the benefit of early detection of CKD, particularly in more susceptible and more disadvantaged groups. Earlier detection and appropriate management of CKD subjects will reduce cardiovascular events and slow further deterioration in renal function in these patients. These measures altogether could defray costs related to eventual ESRD development and higher risk of cardiovascular events.