Biochemical Reference Intervals in Geriatrics

Abstract

Reference intervals are important estimates used to determine whether an individual is healthy or unhealthy. They are the most widely used decision making tool in medicine and heavily influence doctor’s decisions regarding patient care. Despite the abundance of reference interval research in the field of clinical chemistry, age-related reference intervals have yet to be well-established for elderly populations. Many physiological and biochemical changes have been documented to occur with age however limited attempts have been made to quantify these changes. As a result, it is typical in clinical practice to assess geriatric patient data using an adult reference interval. Such practices can result in over-medicalization, unnecessary medical procedures and/or missed diagnoses. This thesis aims to address this gap in literature by summarizing what geriatric reference intervals are available and by investigating how reference intervals are affected by the presence of morbidity, a common characteristic of the elderly. The first chapter of the thesis introduces the reader to reference intervals, summarizes the current guidelines used in their determination and provides a rationale for the use of age-related reference intervals in geriatrics. Chapter 2 presents a systematic review that summarizes all available reference intervals for populations ≥65 years of age and the methodology used in their determination. Despite extreme variability in methodology, evidence suggests that geriatric reference intervals are significantly different from those of adults for many analytes. Chapter 3 presents a study that evaluates the effect morbidity has on reference intervals. In this study data from the National Health and Nutrition Examination Survey (NHANES) was used to calculate age-specific reference intervals for creatinine, a marker of kidney function known to increase with age. Findings suggest that the presence of morbidity significantly increases the upper limit for creatinine in elderly populations. Finally, the concluding chapter summarizes the overall findings of the thesis, proposes areas for future research and reinforces the importance of the above findings.