The occurrence of environmental clusters of Chronic Kidney Disease of uncertain aetiology (CKDu), where there is no known cause for the onset of kidney dysfunction, is a concern globally. Waterborne exposure pathways in the environment may result in indirect or direct ingestion of trace elements with potential health risks. This research examines the relationship between Standardised Incidence Rates (SIRs) of CKDu and the log-ratio balances of Potentially Toxic Elements (PTEs) in regional stream water. Compositional elemental balances were created and regression was used to identify the balances most associated with log-transformed SIR CKDu. At the regional scale, a statistically significant relationship was found between log (CKDu SIR) and the elemental balance Al/As which effectively delineates different geological domains across Northern Ireland. Following stratification by basalt bedrock (the dominant bedrock geology for SIR CKDu), the balance Al/Fe was identified as significantly associated with log (CKDu SIR). Superficial deposits, dissolved organic carbon and pH may act as controls on the balance of Al and Fe. With a high proportion of private water supplies registered in these areas, this research highlights the importance of considering bedrock geology and superficial deposits in understanding multi-element interactions of waterborne environmental toxins and potential links with environmental clusters of CKDu. We would like to acknowledge and thank our esteemed colleague and friend Vera Pawlowsky-Glahn who has been instrumental in the development of this research, pioneering the importance of Compositional Data Analysis (CoDA) in the study of health and the environment. For several of us, Vera provided our first introduction to CoDA and over many years has aided our shared understanding and increased awareness of the need to address the compositional nature of data such as soil and water geochemistry in our research. We are pleased to have this work on the use of compositional balances in exploring the explanatory environmental factors related to chronic kidney disease of uncertain aetiology included in this Festschrift. It represents an exciting field of innovative research where an acknowledgement of CoDA principles is vital if we are to understand fully the critical relationship between our health and the environment.