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Sugarcane workers in northwestern Nicaragua are suffering from chronic kidney disease of non-traditional causes (CKDnt) at extremely high rates. In the small town of Chichigalpa alone, CKDnt causes 46% of male deaths (Kurzrok et al. 2013). This paper examines the CKD epidemic as a fundamentally structural problem, not merely a biological abnormality, because it is closely linked to labor exploitation, poverty, human rights violations, and historical context. Grounded in literature from medical anthropology and medical sociology and based on two months of ethnographic field research in northwestern Nicaragua, it analyzes how knowledge production interacts with scientific uncertainty about CKDs specific biomedical causes. It posits that scientific knowledge does not close controversy, but rather proliferates uncertainties, thereby forestalling the potential for rights claims. A strictly scientific understanding of CKD diffuses responsibility for addressing its structural causes, distracts from structural violence, and diverts attention away from the urgency of CKD deaths.

Metformin is widely used in the treatment of type 2 diabetes mellitus (T2DM). It is largely cleared by the kidneys and according to Product Information, it is contraindicated in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis. The risk of metformin- associated lactic acidosis (MALA), however, is extremely rare. One of the shortcomings of the literature is that the use of metformin in patients with kidney disease and other risk factors for lactic acidosis is largely unknown. In three publications, the aims of this thesis were to investigate the pharmacokinetics of metformin, its usage in patients with CKD and the risk factors for MALA. The population pharmacokinetics of metformin in healthy subjects and patients with T2DM was investigated (Paper 1). Creatinine clearance (CLCR) and body weight were important covariates of the clearance (CL/F) and volume of distribution (VC/F) parameters, respectively. Variant transporters of metformin were not influential covariates. The model was used to simulate maximum daily doses of metformin at each level of kidney function to ensure metformin concentrations remained below 5 mg/L. A study was conducted in patients with CKD (CLCR