Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study

Evidence from epidemiological and clinical literature suggests that ageing contributes to the incidence of reduced renal filtration capacity [1]. In the presence of risk factors during ageing, such as diabetes, hypertension and others, filtration capacity further declines. This concept is underlined by many epidemiological studies showing a decline of measured estimated glomerular filtration rate (eGFR) with advancing age [2]. Kidney function is usually assessed by creatinine-based estimated glomerular filtration rate (eGFR) equations. However, those formulae have a certain degree of inaccuracy when used in older people due to changes in anthropometry and renal physiology during ageing [3]. Alternative filtration markers yielded different eGFR values for different cohorts of people tested [4]. This inaccuracy of laboratory measurements of kidney function suggests a risk of underdetection or overdetection of CKD, especially with advancing age [5]. Indeed, the eGFR threshold at which the risk of negative outcomes increases among older patients is hotly debated [6], and current evidence suggests that such a threshold may be lower among older people compared to adult ones [7‐9]. Additionally, the eGFR cut-offs at which the risk of death starts to increase may change as a function of the equation used among older people [10]. Thus, improving accuracy of CKD screening measures for older populations would be of help in reducing the risk of underdiagnosis to maximize prevention of CKD and its consequences while minimising the risks and cost of overdiagnosis [6].

Diminished kidney function has become a relevant public health burden for all age groups, as CKD frequently results in an increased risk of end stage renal disease (ESRD), morbidity and mortality [11]. Besides “traditional” endpoints, CKD has been shown to impact nutritional status, inflammatory processes and anemia [12], thereby affecting different outcomes especially relevant to older people. These include impaired physical function, frailty and disability [13‐16], cognitive impairment and dementia [17‐19], depression [20‐22], sensory impairment [23], undernutrition and sarcopenia [24‐26], and adverse drug reactions (ADRs) [27, 28]. Therefore, early and sensitive detection of diminished renal function is essential to individually address care needs of older people with CKD and to address one of the major health burden in public health for the incoming decades [29].

Incorporating scoring risk models for care planning of older people at risk for CKD has come into focus recently [30]. Risk prediction models are generally based on equations designed on the basis of prognostic factors and clinical outcomes, available at the time the prediction is made, and collected in specific and representative cohorts of individuals followed up for a given period of time [31]. Built on evidence of such models, screening programmes for CKD can take into account the characteristics of the target population in addition to simple laboratory measures, biomarkers and disease-based investigations. Multi- and co-morbidity, polypharmacy, frailty, functional and cognitive impairment and disability should be considered as part of a patient centered approach in CKD management especially in older adults [15, 23‐26, 32‐35].

So far, no CKD screening program has included all those variables also including data from comprehensive geriatric assessment (CGA), the only assessment technology able to capture the numerous domains of health status and their complex interactions in older people. Accordingly, the need for laboratory measurements able to identify accurately older people with CKD is a demand to address the public health challenges arising from the current demographic shifts. Indeed, this view is widely shared by the geriatric and nephrology communities, both in EU and USA [36, 37].

The aims of this multicenter study in Europe are to assess existing methodologies for CKD screening and investigate existing and innovative biomarkers of CKD in older persons. Furthermore, the Screening for CKD among Older People across Europe (SCOPE) study will provide evidence for including physical and functional health parameters of older people across Europe and help design a tailored risk prediction model for CKD in old age.

The SCOPE study is one of the largest prospective observational cohort studies aimed at screening for CKD among older persons across Europe. The current paper outlines the study protocol including statistical analysis of data, risk prediction modeling and economic evaluation of costs arising from CKD during the advanced ageing process.

The strength of the protocol outlined in this paper is the real life setting for recruitment of participants. All persons with age ≥ 75 years attending the outpatient services at participating institutions will be requested to participate in the study. No other inclusion criteria will be considered. This seems the primary strength of the SCOPE study. The collection of real life data in a longitudinal fashion over a two- years period of time will allow insight on the impact of renal function on the management and advanced care planning of older subjects prone to renal impairment.

It is expected that many of the participants enrolled will be affected by multimorbidity [64]. The impact of disease clusters and management strategies from experts in the field of nephrology and geriatrics will open access to comparative effectiveness analysis of data and interventions [65]. People older than 75 years or people with impaired renal function have so far been rarely included into clinical trials. Aging population heralds a new geriatric “reality”, namely an increase in older adults with CKD. Conversely, many older adults are living healthy and active, even with several chronic conditions. In this context longitudinal epidemiological studies are extremely valuable tools in observational research and have many uses and strengths [66].

Multimorbidity, and in this context CKD have been shown to impact functional status, especially of older patients [66]. The systematic use of a CGA makes possible the investigation of multiple domains of health status in older persons. CGA is part of clinical practice of Geriatric Medicine [67] and is also useful in research investigating consequences of CKD [68, 69] since it has been shown to affect different kind of outcomes relevant to older people. The inclusion of functional domains, as recently postulated by the World Health Organization (WHO) [70] in the design of screening models for CKD in older persons aligns the SCOPE projects with future demands for all Health Care systems around the globe [71, 72]. Health care is currently provided and funded on a disease-centered approach in many health care systems. The inclusion of CGA in the longitudinal evaluation of study participants of the SCOPE project will allow a more patient-centered and individualized approach for screening and advanced care planning for older subjects prone to kidney function decline [31, 69]. Furthermore, the search for biomarkers which are less influenced by muscle mass and more accurate in predicting outcomes compared to circulating creatinine is of special interest and will be further investigated. Thus, combining the use of CGA and the investigation of novel and existing independent biomarkers in within the SCOPE project, could help in building new evidence in the development of recommendations and guidelines for a patient-centered approach in the screening and management of older people at risk for CKD.

The alignment of an economic evaluation of care pathways and histories of study participants during the study period will give new input for care providers and planners in different health care and funding systems. Inclusion of costs of screening to achieve accurate diagnosis of CKD and related follow-up costs (e.g. pharmacological treatment, specialist visits, laboratory visits over the 2-year follow-up) will answer current call for actions coming from different bodies [73]. The focus on CKD related consumption of healthcare resources (e.g. emergency room access, hospital admission, hospital out-patient care referrals, nursing home placements, use of home care services and others) using Markov modelling will provide key information for developments in public health.

Major drawback or limitation of the project is the lack of standardized management and care plans for older people currently available for all participating centres. Centres enrolling participants in the SCOPE projects are highly experienced in the management of older multimorbidity subjects at risk for renal impairment and related clinical complications, including changes in functional status. Guidelines on CKD management are mainly disease-centred and put a focus on morbidities and mortality. It is to be foreseen that the care pathways for participants will therefore still be tailored individually and according to needs, driven by expertise of staff in the participating centres. However, important information may be expected though, as the implementation of the CGA per se into care pathways has already been proven effective [67]. It seems noteworthy that the individualized care approach during complex care management of older subjects is part of daily routine in geriatric medicine. Alignment of care processes along CGA results seems feasible in the context of current scientific evidence.

In conclusion, the SCOPE project will close essential gaps in the care of older people with declining kidney function. Due to the extremely comprehensive study setting and data analysis it is to be expected that evidence arising from the SCOPE project will impact the management of older people suffering from CKD, as well as the quality of care delivered for older subjects at risk for CKD in daily routine. The high quality of data retrieved will however, also open doors for new research and innovation in the field of nephrology and geriatrics. Building on solid evidence arising from the current project, SCOPE will support the development of European recommendations and guidelines, as well as a European education program in the field of screening and management of CKD in older adults across Europe.