International Collaboration for the Epidemiology of eGFR in Low and Middle Income Populations - Rationale and core protocol for the Disadvantaged Populations eGFR Epidemiology Study (DEGREE)

Abstract

BackgroundThere is an increasing recognition of epidemics of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low- and middle-income countries (LMICs). Although it is currently unclear whether there is a unified underlying aetiology, these conditions have been collectively termed CKD of undetermined cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young men and women over the last 2 decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these condition (s). International comparisons have provided the first steps in understanding many chronic diseases, but such comparisons rely on the availability of standardised tools to estimate disease prevalence. This is a particular problem with CKD, since the disease is asymptomatic until the late stages, and the biases inherent in the methods used to estimate the glomerular filtration rate (GFR) in population studies are highly variable across populations.MethodWe therefore propose a simple standardised protocol to estimate the distribution of GFR in LMIC populations – The Disadvantaged Populations eGFR Epidemiology (DEGREE) Study. This involves the quantification of renal function in a representative adult population-based sample and a requirement for standardisation of serum creatinine measurements, along with storage of samples for future measurements of cystatin C and ascertainment of estimates of body composition, in order to obtain valid comparisons of estimated GFR (eGFR) within and between populations.DiscussionThe methodology we present is potentially applicable anywhere, but our particular focus is on disadvantaged populations in LMICs, since these appear to be most susceptible to CKDu. Although the protocol could also be used in specific groups (e.g. occupational groups, thought to be at excess risk of CKDu) the primary aim of the DEGREE project is characterise the population distribution of eGFR in multiple regions so that international comparisons can be performed. It is only with a standardised approach that it will be possible to estimate the scale of, and variation in, impaired kidney function between affected areas. These data should then provide insights into important social, demographic and environmental risk factors for this increasingly recognised disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0417-1) contains supplementary material, which is available to authorized users.

Causal Inference in Environmental Epidemiology: Old and New Approaches

“…Ecologic studies have played a key role in identifying that arsenic in drinking water is a cause of cancer [26]. Similarly, international comparisons of the prevalence of chronic kidney disease of unknown cause (CKDu) are playing a crucial role in the search for the causes of this major public health problem [27].…”

CKD and CKDu in Northern Peru: a cross-sectional analysis under the DEGREE protocol

“…We de ned three categories of kidney function based on eGFR results: moderate or established kidney dysfunction (< 60 mL/min/1.7 m 2 ), mild kidney dysfunction (60-90 mL/min/1.7 m 2 ), and normal (≥ 90 mL/min/1.7 m 2 ). CKD was de ned as the proportion of individuals with moderate or established kidney function (eGFR < 60 mL/min/1.7 m 2 ) in the overall sample; whereas the prevalence of CKDu was estimated using the same indicator but excluding individuals with previous diagnosis of HT and/or T2DM, and those having a heavy proteinuria, de ned as 3 + in urine dipstick (equivalent to ≥ 300 mg/dl of protein) according to the DEGREE protocol [20].…”

“…A cross-sectional study found CKDu prevalence in most affected areas of Sri Lanka was as high as 22.9% [26]. Globally, the increasing prevalence of end-stage CKD in African American, Hispanic and Native American populations is at least 50% attributable to T2DM [20]. In contrast, the contribution of CKDu to overall CKD burden in Peru seems to be negligible.…”

Chronic kidney disease of unknown or nontraditional origin: a new global epidemic?

“…Hay otra colaboración internacional multicéntrica, liderada por epidemió-logos del London School of Hygiene and Tropical Medicine, para aplicar un cuestionario corto y pruebas de función renal según el protocolo estandarizado del Disadvantaged Populations eGFR Epidemiology Study (DEGREE), buscando determinar dónde y quiénes están afectados, y encontrar indicios sobre etiología a ser investigados más a fondo en estudios con diseños analíticos. Ojalá muchos de los países mencionados participen en DEGREE 15 .…”