In Mexico, the kidneys of poor and marginalised communities are failing with little warning and no explanation. Commonly referred to as Chronic Kidney Disease of Unknown Origin (CKDu), this new variant of kidney disease has been described as a ‘medical enigma’. CKDu cannot be accounted for in conventional aetiological terms but is variously held to be a consequence of aggressive economic development, environmental degradation and precarious working and living conditions. Drawing on two interconnected ethnographic studies, and intertwining problems of cause and care, this paper will: (1) document the social conditions of disease emergence around Lake Chapala, Central Mexico and (2) follow the haphazard routes kidney patients take to access resource-intensive biotechnical treatments. As they carry the costs (moral, social and economic) and the burden of care, the practices of Mexican patients and their families – those with minimal social protection and entitlement – offer a critical vantage point from which to assess the dynamic interplay between the state, the market and the sick body. CKDu constitutes a contemporary (bio)scientific controversy, one which acquires its relevance within a political economy of harm.