Challenges and opportunities in interventions for chronic kidney disease of unknown origin (CKDu): report from the International Society of Nephrology Consortium of Collaborators on CKDu
Brendan Smyth1,2 , Jason Glaser3 , Jaime Butler-Dawson4,5 , Nishantha Nanayakkara6 , David H. Wegman3,7 , Shuchi Anand8 and Adeera Levin9
1 National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia;
2 Department of Renal Medicine, St George Hospital, Kogarah, New South Wales, Australia;
3 La Isla Network, Washington, District of Columbia, USA;
4 Center for Health, Work, and Environment, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;
5 Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA;
6 Nephrology and Transplant Unit, National Hospital, Kandy, Sri Lanka;
7 Department of Work Environment, University of Massachusetts Lowell, Lowell, Massachusetts, USA;
8 Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, California, USA;
9 Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
Chronic kidney disease of unknown origin (CKDu) is a progressive tubulointerstitial nephropathy reported principally in agricultural communities, specifically manual laborers in dry, lowland regions of Central America, Sri Lanka, and Southern India.1,2 Further research may reveal whether it is present, but unrecognized, in other regions, including in parts of South East Asia, Africa, and the United States.
The disease was first described 2 decades ago, and although scientists largely agree on common clinical characteristics, much of the pathophysiology remains unclear. A leading hypothesis is occupational exposure to recurrent heat stress leading to recurrent acute kidney injury (AKI), the risk for which may increase in parallel with increasing global temperatures.3 Other hypothesized factors include environmental toxins, genetic predisposition, and dietary or pharmaceutical exposures, or some combination thereof. Persisting uncertainty has led researchers to focus on pathogenesis and epidemiology. However, ongoing disease burden, especially given a lack of access to effective treatments, and the potential for affected populations to experience research fatigue, demands that efforts to prevent and treat CKDu are undertaken as a priority. Interventional study designs that test preventative strategies and focus on addressing the concerns of affected populations offer a path forward. Although challenging to design when etiological uncertainty persists, interventional studies can be a strong test of a causal hypothesis and such studies may also advance our understanding of CKDu pathophysiology while potentially benefiting affected populations.
In 2016, the International Society of Nephrology convened the International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology, which has reported on disease detection strategies2 and on methods to elucidate the cause of CKDu.1 Recognizing the urgent need for preventative and disease-modifying therapies, International Consortium of Collaborators on Chronic Kidney Disease of Unknown Etiology presents this commentary as a starting point for researchers seeking to mitigate the burden of CKDu. We acknowledge the challenges inherent to interventional research in this area, while emphasizing the need for unbiased evidence and the various study designs and other solutions that can be employed.