24-Hour Urinary Chemistries and Kidney Stone Risk

Rationale & Objective: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape. Study Design: Prospective cohort study. Setting & Participants: We analyzed 9,045 24- hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II. Exposure: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium. Outcome: Incident symptomatic kidney stones. Analytical Approach: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection fl ection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor. Results: Each urinary factor was significantly fi cantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection fl ection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified fi ed 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium). Limitations: Predominantly White participants, lack of information on stone composition. Conclusions: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation.