  Recent experimental work on the nephrotoxicity of contaminants in drinking
water using laboratory mice, motivated by the need to understand the origin of
chronic kidney disease of unknown aetiology is examined within our
understanding of the hydration of ions and proteins. Qualitative considerations
based on Hofmeister-type action of these ions, as well as quantitative
electrochemical models for the Gibbs free-energy change for ion-pair formation
are used to explain why Cd$^{2+}$ in the presence of F$^-$ and water hardness
due to Mg$^{2+}$ ions (but not Ca$^{2+}$) can be expected to be more
nephrotoxic, while AsO$_3^{3-}$ in the presence of F$^-$ and hardness may be
expected to be less nephrotoxic. The analysis is applied to a variety of ionic
species typically found in water to predict their likely combined
electro-chemical action. These results clarify the origins of chronic kidney
disease in the north-central province of Sri Lanka. The conclusion is further
strengthened by a study of the dietary load of Cd and As, where the dietary
loads are found to be safe, especially when the mitigating effects of
micronutrient ionic forms of Zn and Se, as well as corrections for
bio-availability are taken in to account. The resulting aetiological picture
supports the views that F$^-$, Cd$^{2+}$ (to a lesser extent), and Mg$^{2+}$
ions found in stagnant household well water act together with enhanced
toxicity, becoming the most likely causative factor of the disease. Similar
incidence of CKDu found in other tropical climates may have similar geological
origins.
