Chronic kidney disease (CKD): a study of prevalence in the community

Chronic kidney disease (CKD) is a common condition, particularly among the elderly, characterized by slowly progressive reduction in renal function. Ultimately – though not inevitably – CKD can lead to end-stage renal failure, when survival depends on renal replacement therapy, that is: regular hemodialysis or kidney transplantation. Advancing age, diabetes, hypertension and obesity are the major risk factors for CKD, so with an ever-ageing population and increasing prevalence of diabetes and obesity, CKD is a major and growing health problem around the world, with a current estimated annual cost to the National Health Service (NHS) in the UK of £1.4 billion.

Diagnosis of CKD and staging of its severity depends on two laboratory tests: serum creatinine concentration and urine albumin concentration. Serum creatinine allows estimation of glomerular filtration rate (eGFR), a parameter of prime clinical importance because it defines kidney function. In health eGFR is maintained >90 mL/min/1.73m². All those with loss of kidney function, no matter what the cause, have reduced eGFR and severity of CKD correlates with eGFR reduction. In health, the protein albumin is usually undetectable or barely detectable in urine, but loss of kidney function (i.e. CKD) is associated with increasing loss of albumin in urine (albuminuria). The parameter usually used to monitor this aspect of kidney function is the urine albumin: creatinine ratio (ACR), which in health is <3 mg/mmol.

Internationally agreed (KDIGO) guidelines define how eGFR and ACR results are used to exclude CKD, diagnose CKD, and determine severity of CKD. CKD is excluded if eGFR is >60 mL/min/1.73m² and ACR is <3 mg/mmol unless there is other evidence of renal disease. The guidelines define five stages of increasing renal dysfunction (CKD severity) based on eGFR result:

• eGFR >90 indicates normal kidney function but CKD stage 1 would be diagnosed if there is other evidence of renal dysfunction
• eGFR 60-89 is defined as mild dysfunction but CKD stage 2 would be diagnosed only if there was other evidence (e.g. ACR >3.0 mg/mmol/L) of renal damage
• eGFR 45-59 is defined as mild to moderate dysfunction – CKD stage 3a
• eGFR 30-44 is defined as moderate to severe dysfunction – CKD stage 3b
• eGFR 15-29 is defined as severe dysfunction – CKD stage 4
• eGFR <15 is defined as renal failure – CKD stage 5

KDIGO guidelines advise that a diagnosis of CKD should only be made if abnormal eGFR or ACR is confirmed no less than 3 months after initial testing.

CKD is asymptomatic in the early stages (1-3) when it can only be detected by blood/urine testing (eGFR/ACR), so there are many patients with early-stage CKD who, because they have never been tested, remain undiagnosed. Early diagnosis of CKD is important because treatment modalities may be beneficial in terms of reduced morbidity and mortality; treatment could either prevent or delay progression to symptomatic CKD and the need for life-changing, expensive renal replacement therapy. It remains unclear just what proportion of the elderly population have CKD, but remain undiagnosed.

Better understanding of the prevalence of CKD (both diagnosed and undiagnosed) in the elderly is afforded by this highlighted published data from the Oxford Renal Longitudinal Cohort (OxRen) study.

A total of 3207 individuals aged >60 years were recruited from 44 primary care (GP) clinics in Oxfordshire UK, for entry to the OxRen study cohort. Entry to the study cohort was automatic for 327 of the 3207 individuals who had a confirmed pre-existing CKD diagnosis recorded in GP records. For the remaining 2880, which included 109 patients with an unconfirmed CKD diagnosis recorded in GP medical records, entry to the study cohort depended on eGFR and ACR results obtained during a two-stage screening process. During the first stage of screening individuals with eGFR >60 and ACR <3 (i.e. normal renal function) were excluded from further study. All those with abnormal result (eGFR <60 and/or ACR ≥3) were submitted for second confirmatory screening 3 months later. A diagnosis of CKD was only made if second round of screening revealed abnormal result (eGFR <60 and/or ACR ≥3). If on second screening an individual had only one positive result from the two-stage screening process, that individual was classified as having borderline/transient decreased renal function.

As a result of this two-stage screening process, 2346 of the 2880 (81 %) screened were found to have normal renal function; 277 (9.6 %) were found to have borderline/transient decreased renal function; and 257 (8.9 %) were found to have newly diagnosed CKD.

So, taking the whole initial study population (n=3207), 327 (10.2 %) had pre-existing CKD and 257 (8.0 %) had newly diagnosed CKD, giving on overall CKD prevalence of 18.2 % among this UK population aged >60 years. Of the 584 with confirmed CKD, 44 % were diagnosed as a result of the screening process. The implication is that in the UK and maybe in other parts of the developed world, close to half of those aged >60 years who have CKD, remain undiagnosed.

The final OxRen CKD study cohort comprised 861 individuals (584 with confirmed CKD and 277 with borderline/transient renal dysfunction). Baseline assessment of the 861 individuals included measurement of eGFR and ACR which allowed CKD staging according to KDIGO criteria. Results of this testing revealed that: 34 (4 %) had CKD stage 1; 122 (14.2 %) had CKD stage 2; 246 (28.6 %) had CKD stage 3a; 133 (15.5 %) had CKD stage 3b; 67 (7.8 %) had CKD stage 4; and one (0.12 %) had CKD stage 5. The remaining 258 (30 %) met the KDIGO definition of normal renal function (eGFR ≥60 mL/min/1.732 and ACR <3 mg/mmol/L).

In addition to blood/urine testing for eGFR/ACR, baseline assessment included collection of the following details for each of the 861 individuals: age, gender, body weight, height, BMI, waist and hip circumference, educational status, smoking status, alcohol use, comorbidities, and blood pressure. Each study participant was invited to complete a lifestyle questionnaire that focused on perceived quality of life, diet, physical activity; it included questions that allow cognitive assessment.

This baseline data is presented in a form that allows comparison between the three groups identified during the screening process: existing CKD; newly diagnosed CKD; and borderline transient decreased renal function.

Future follow-up of the OxRen study cohort (currently expected to be at least 10 years) will lend on this baseline data to explore factors that are involved in the highly variable observed rate of CKD progression; and maybe identify those elderly patient groups for whom early CKD screening would be most beneficial.

The study also provides data surrounding a rather technical issue to do with calculation of eGFR from serum creatinine, a topic that has exercised the nephrology research community for many years. There are two main formulae for calculation of eGFR from serum creatinine; the first, which was validated in 1999, is called the Modification of Diet in Renal Disease (MDRD) equation and the second, validated in 2009, is called the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Since eGFR was calculated using both equations in the OxRen study, it provides data that can inform the ongoing discussion about how best to calculate eGFR, and how the calculation used can affect prevalence of CKD, particularly early-stage CKD. These issues are addressed by the authors in discussion of their study.