There are numerous secondary care datasets investigating CKD. Internationally, the largest of the studies have been included as part of the CKD prognosis consortium (63); these studies typically have at least 1,000 participants and information at baseline on eGFR and albuminuria. The studies included in the CKD prognosis consortium can be broadly divided into three types; general population, high risk cohorts selecting people at high cardiovascular risk and cohorts specifically selecting subjects with CKD. Additionally, whilst the populations covered are diverse, the consortium recognise that some ethnicities are under-represented; black populations are mainly from within the USA and asian populations are predominantly Eastern Asian (63). Even if it were possible to obtain permission for the use of these data, the applicability of these data to the local West Midlands’ population is limited.
A further global network of CKD cohorts, the international network of CKD disease cohort studies (iNET-CKD), includes twelve prospective cohort studies and two registries covering 21 countries (168). The goals of iNET-CKD are the ability to provide mutual assistance and shared expertise through sharing research tools and technologies, to provide opportunities for collaborative research and to enhance training of both young investigators and seasoned researchers.
In addition to the studies identified in the CKD prognosis consortium or iNET-CKD, several international studies have recruited, or continue to recruit, adult patients with CKD across wide geographical areas in order to explore the determinants associated with CKD progression. These studies, and their objectives, are listed in Table 1-7.
Table 1-7. Key international studies investigating progression in adult CKD
Cohort Population Aims Year
recruitment commenced
Number recruited Canadian study of prediction of
death, dialysis and interim cardiovascular events (CanPREDDICT) (169)
eGFR 15-45 ml/min/1.73m2 from outpatient nephrology clinics across Canada
1. To examine the role of both traditional risk factors and a select panel of newer, non-traditional serum and urine biomarkers, in the progression of kidney disease and CVD in patients with CKD, alone and separately. 2. To develop robust predictive models to discriminate between high and low risk patients.
2008 2546
Chronic Kidney Disease Japan Cohort (CKD JAC) (170)
Japanese (or Asian patients living in Japan) adults with eGFR 10- 59m/min/1.73m2
1. To identify risk factors for progression of CKD in Japanese subjects. 2. To identify the impact of CKD on HRQL. 3. To assess the frequency of hospitalisation and economic impact of CKD
2007 2977
Chronic Renal Insufficiency Cohort (CRIC) (171)
Secondary care, all CKD stages To identify risk factors for the progression of CKD and the
development of CVD. 2. To develop predictive models to identify high- risk subgroups, informing future treatment trials and increasing application of available therapies.
Table 1-7 continued…
Cohort Population Aims Year
recruitment commenced
Number recruited French CKD-renal epidemiology
and information network cohort (CKD-REIN) (172)
eGFR 15-59 ml/min/1.73m2 from nephrology clinics
1. To assess the interaction between psychosocial, environmental, biological and genetic factors with outcomes. 2. To assess new
biomarkers to predict outcomes. 3. To evaluate provider practices and their relation with outcomes including PROMs. 4. To identify and quantify costs, and cost
effectiveness, of different treatment practices.
2014 3600*
German CKD study (GCKD) (173)
Secondary care, eGFR 30- 60ml/min/1.73m2 or significant proteinuria (albuminuria
>300mg/day or proteinuria > 500 mg/day) with a
eGFR>60ml/min/1.73m2
1. To identify and validate risk factors for progression of CKD, the development of CVD, and the relationship between CKD and CVD. 2. To determine gender based differences in risk. 3. To assess impact of CKD on HRQL.
2010 4914
Abbreviations: CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR: estimated glomerular filtration rate; HRQL, health related quality of life; PROMs, patient reported outcome measures. * Signifies recruitment in progress.
Given the limitations, and potential lack of applicability, of the datasets described above, the use of UK based CKD studies may be better suited to answering my research questions. Currently there is no national secondary care CKD cohort. A summary of selected, prospective, observational UK studies of CKD, selected as they had at least a two year follow up period and greater than 250 participants, are
discussed below.
1.10.3.1 Chronic Renal Impairment in Birmingham (CRIB) (174, 175)
This study was designed before the K/DOQI CKD staging system was introduced in 2002. CRIB recruited 369 individuals with CKD (serum creatinine greater than 130 μmol/L) from a single centre in Birmingham alongside control groups to investigate the relationship between kidney function and cardiovascular risk factors patients with CKD not requiring renal replacement therapy. Patient follow up was a mean of six years; no further clinical assessment took place during that period, the outcomes reported were ESRD and all cause mortality.
1.10.3.2 Chronic Renal Insufficiency Implementation Study (CRISIS) (176-178) A single centre study from Manchester, CRISIS aimed to recruit patients 18 years and older who were referred for management of CKD and had an eGFR below 60
ml/min/1.73m2 but had no immediate requirement to start dialysis. Recruitment started in 2002 and, by 2015, over 3000 patients were enrolled. Patients were managed in accordance with standard clinical practice guidelines and followed until death or initiation of RRT (dialysis or transplantation).
1.10.3.3 Renal Risk in Derby (R2ID) (179)
R2ID study commenced recruitment in 2008 and is a collaboration between primary and secondary care researchers. It is a primary care cohort of patients with stage G3 CKD (30-59 ml/min/1.73m2) who were recruited directly from 32 participating primary care practices. It was created to examine the renal and cardiovascular risks associated with less advanced CKD, and included measurements of vascular health including PWV (Section 2.4.4.2) and advanced glycation end products (Section 2.4.4.3).
1.10.3.4 Renal Impairment in Secondary Care Study (RIISC) (73, 180) The UK based secondary care studies discussed above all had relatively broad
inclusion criteria, whether the study was based in primary or secondary care. In order to focus on the individuals at the greatest risk of progression of renal disease, our group designed the RIISC study. This focuses on advanced and/or progressive CKD and includes detailed bioclinical phenotyping collected using standard operating procedures (SOPs) within an ethnically diverse population. The RIISC study is discussed in detail in the methods section.