Chronic Kidney Disease of unknown cause (CKDu) in disadvantaged communities in low-and-middle income countries (LMICs)

There is an epidemic of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low-and-middle income countries (LMICs). This was featured recently in Science which reported previous work of some of the current applicants. Although it is currently unclear whether there is a unified underlying aetiology, these conditions have been collectively termed CKD of unknown cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young men and women in LMICs over the last two decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these condition(s) and to develop preventive interventions.

Currently it is known that CKDu exists in Central America and mainly affects male rural agricultural workers. It may also be occurring in other tropical/subtropical parts of the world, but standardized data are not available for comparison, and also it is not known which population subgroups it affects. Obtaining this information is an essential step towards discovering the cause(s) of CKDu.

We have recently established a partnership involving a practical protocol to estimate distributions of renal function in disadvantaged communities: the Disadvantaged populations estimated glomerular filtration rate (eGFR) epidemiology study (DEGREE). This will provide key information to inform hypotheses and to guide further research into the causes of CKDu.

The Foundation Award will enable this partnership to make a step-change by implementing the prevalence survey protocol (and a related validation study) in four centres (India, Malawi, Peru, Mexico) in three tropical/subtropical regions (Asia, Africa, and Latin America) where the disease is likely to be endemic. This will provide the basis for developing further studies to discover the cause(s) of CKDu, and developing interventions to prevent it.

There 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). It is currently not possible to determine if the condition has similar characteristics or similar causes in different parts of the world. International comparisons are made more difficult because CKDu is usually clinically silent until it has progressed to advanced stages, so the diagnosis must be made by testing asymptomatic individuals.
There is a critical need for a more comprehensive and integrated approach to this problem, involving standardized validation, prevalence and risk factor studies, including comparisons between and within tropical/subtropical regions of the world.

We have recently established a collaboration involving a practical protocol to estimate distributions of renal function in disadvantaged communities: the Disadvantaged populations estimated glomerular filtration rate (eGFR) epidemiology study (DEGREE). This will provide key information to inform hypotheses and to guide further research into the causes of CKDu.

The Foundation Grant involves undertaking the DEGREE project in four centres (India, Malawi, Peru, Mexico) in three regions (South Asia, Latin America, Sub-Saharan Africa) where the disease is likely to be endemic. In each centre we will conduct a prevalence and risk factor survey in an urban and a rural area (the exception is Mexico where an urban survey is not possible because of the security situation), and we will also undertake a validation study to refine our approach to estimate GFR for cross-population comparisons.

Chronic Kidney Disease of unknown cause (CKDu) affects vulnerable populations, many of whom are migrants. Impacted communities are so under resourced that the disease may have persisted for decades (goo.gl/7gQq3Y) without a functioning surveillance or treatment strategy in place, and may be more widespread than previously thought. It is essential to take a coordinated international approach to further understanding of this disease(goo.gl/dhLFX3)( goo.gl/EBV5LI), and the Foundation Award will enable this to be done for the first time.

The DEGREE study will enable standardized comparisons of impaired kidney function between and within tropical/subtropical regions of the world, in urban and rural areas. DEGREE will form the basis for further etiological research, surveillance of time trends, the implementation and evaluation of interventions. It will thereby aid countries, companies and development organizations in addressing the disease adequately.

Community organizations, research institutions and governments (Neil Pearce is an Advisor to the Sri Lankan government and WHO on CKDu), will be engaged to ensure that information on the DEGREE program, CKDu and appropriate treatment options are available. A DEGREE website will provide the protocol, research materials and information with which local researchers and other actors can empower themselves. Feedback and reporting of areas with endemic CKDu will allow us to build an international network both in terms of research, but also in terms of action on CKDu. Culture-specific written materials will also be distributed through on-the-ground community organizations so that relevant information can reach the affected populations.

Engagement with policy makers in impacted industries and within governments will be of high priority. We will assist the relevant authorities in establishing ongoing surveillance (Neil Pearce is already advising the Sri Lankan government on this), to understand 'who' is affected and 'where'. The La Isla Foundation has a track record of successfully working with governments to push policy forward as in Costa Rica (goo.gl/mpFn2e).

The potential burden of CKDu will undermine already tenuous economies in affected countries. Workers with CKDu produce goods consumed in Europe. Thus, knowledge about CKDu should inform foreign aid policy and help the UK to protect those along supply chains that support its economy. Communication materials developed by our team and excellent relationships with journalists and filmmakers from publications such as the Guardian (goo.gl/wOycrj),( goo.gl/aMDm1n) , Science(goo.gl/0lznPX) and National Geographic(goo.gl/1DxWg0) will inform a wide audience.

CKDu is potentially a global epidemic. DEGREE will support resource allocation and policy development to further assess the population burden, identify the causes, treat, and prevent this disease. This is the first strategic initiative with which to address CKDu and will impact actors along supply chains and throughout societal strata.