Urine Volume And The Incidence Of Kidney Stones
Kidney stone disease poses a significant health challenge, impacting nearly one in 11 individuals in the United States. Not only does it result in substantial morbidity, but it also leads to a considerable utilization of healthcare resources.
In the pursuit of preventing stone disease, a longstanding and widely endorsed strategy involves increasing fluid intake to augment urinary volume. Both the 2019 AUA kidney stone guidelines and the 2021 EAU stone prevention guidelines advocate for maintaining a daily urine volume of at least 2.5 L.
The foundation of these recommendations rests significantly on a pivotal study by Borghi et al. in 1996, a prospective randomized clinical trial. This influential research demonstrated that patients engaged in a high fluid intake program, aiming for a target urine volume exceeding 2 L daily, experienced a remarkable 50% reduction in stone recurrence rates and prolonged intervals between stone recurrences compared to controls.
Despite subsequent studies supporting the benefits of heightened fluid intake for nephrolithiasis prevention, their impact is tempered by limitations, as underscored by a recent Cochrane review. This comprehensive analysis identified the Borghi study as the sole research meeting stringent inclusion criteria, while also revealing potential biases, including selection, performance, detection, and reporting bias.
To gain a better understanding of this important aspect, the researchers conducted a thorough analysis using data from the Registry for Stones of the Kidney and Ureter (ReSKU), a unique UCSF database. The researchers wanted to gain a deeper understanding of the relationship between the initial 24-hour voided volume and the incidence of reported stone events by examining outcomes and 24-hour urine data from this unique resource.
Overview of the Study
The study aims to investigate the widely recommended practice of increasing fluid intake for the prevention of kidney stones. Specifically, it focuses on the belief that higher voided volume plays a role in diminishing the recurrence and severity of stones. The goal is to assess the existing evidence supporting this notion, considering the current limited body of supporting research.
Methods
Starting in 2015, individuals seeking treatment for stone disease at the University of California San Francisco (UCSF) Urology clinic were included in the Registry for Stones of the Kidney and Ureter (ReSKU) database. This database, characterized as a prospective and high-quality automated nephrolithiasis registry, systematically extracts relevant data directly from the electronic health record (EHR). The comprehensive enrollment protocol and associated details have been extensively outlined in previous documentation.
Data pertaining to nephrolithiasis outcomes was accessible for patients spanning the years 2015 to 2020. Inclusion criteria for this study involved patients who were enrolled in the ReSKU database and had undergone at least one prospectively collected 24-hour urine test, specifically the Litholink 24-hour urine test provided by Labcorp. Surgical procedures considered in the analysis comprised percutaneous nephrolithotomy (PCNL), ureteroscopy (URS), extracorporeal shock wave lithotripsy (ESWL), cystolitholapaxy, open stone removal, and lap/robotic stone removal. Notably, individuals with cystine stones were excluded from the analysis.
Prior to participation, all enrolled patients provided informed consent, and the study received approval from the University of California San Francisco institutional review board and Human Research Protection Program (Protocol 14-14533). The research adhered to ethical standards outlined in the Declaration of Helsinki.
In addition to demographic data, several key variables were scrutinized as part of the study. Patient age, race, gender, and body mass index (BMI) were included in the analysis. The 24-hour urine data encompassed voided volume, 24-hour urine sodium (Na24) serving as a surrogate for dietary sodium intake, and creatinine per kilogram (CrKg24) acting as a surrogate for kidney function.
The primary outcome under investigation was the number of stone events, distinctly characterized as either the asymptomatic passage of stones or the occurrence of a surgery for stone removal. To mitigate the risk of overcounting attributable to incomplete clearance of stones due to technical or surgical factors, a careful approach was taken. Patients experiencing a symptomatic stone episode without the passage of stones, coupled with a subsequent stone removal surgery within 90 days of that episode, were considered as a singular stone event. This meticulous methodology aimed to ensure precision in capturing the genuine occurrence of nephrolithiasis events within the study population.
To assess the significance of various factors, nonparametric statistical analyses were employed in this study. The Mann–Whitney test was utilized for comparing continuous variables between two groups, while the Kruskal–Wallis analysis of variance tests were employed for three groups. Categorical variables between two groups were compared using Chi-squared tests, providing a comprehensive examination of different types of variables.
In order to delve into the nuanced impact of voided volume on stone events, a multivariable logistic regression analysis was conducted. This analysis allowed for the determination of the influence of voided volume while accounting for potential confounding factors such as gender, age, BMI, CrKg24, and Na24. The aim was to discern the independent contribution of voided volume to the occurrence of stone events, considering the interplay of these various demographic and physiological factors.
To further explore the associations, Spearman correlations were employed. These correlations were specifically conducted to elucidate the relationship between voided volume and stone events across different primary stone compositions. This granular analysis aimed to provide insights into potential variations in the impact of voided volume on stone events based on the composition of the stones.
All statistical analyses were executed using R 3.4.0 from the R Foundation in Vienna, Austria, ensuring robust and reliable results. The validity of the findings was confirmed through the use of GraphPad Prism v7, contributing to the overall rigor and credibility of the study’s statistical approach.
Results
The study, conducted on 450 patients from 2015 to 2020 within the ReSKU dataset, provided valuable insights into the relationship between voided volume and stone events. The cohort’s demographic and clinical characteristics revealed that 51.8% were men, 63% were White/Caucasian, with a median BMI of 25.8 kg/cm² and a median CrKg24 of 19.8 mg/kg/24 h. The median 24-hour voided volume was 2.1 L, and 43.6% had one stone event, while 56.4% experienced two or more stone events.
Notably, the analysis found no significant difference in 24-hour voided volume between patients with one stone event and those with two or more stone events (Kruskal–Wallis p=0.06). Multivariable logistic regression analysis indicated that female gender (OR 1.93, 95% CI 1.25–3.00, p=0.0031) and higher BMI (OR 1.04, 95% CI 1.00–1.08, p=0.03) were associated with multiple stone events, while voided volume did not exhibit a significant association (OR 1.04, 95% CI 0.83–1.33, p=0.68).
Furthermore, sodium intake (Na24) and kidney function (Cr24Kg) were found to be highly correlated with voided volume (R=0.31 and 0.22, respectively, p<0.0001 for both). A subset of 205 patients with at least two 24-hour urine tests showed minimal change in voided volume between the two collections. Importantly, no significant difference in the average change in voided volume was observed between patients with one stone event and those with two or more stone events (Kruskal–Wallis p=0.82).
The analysis was refined by considering primary stone composition, revealing a statistically significant negative correlation between voided volume and stone events in calcium oxalate dihydrate stone formers (Spearman R=-0.42, p=0.04). These findings contribute nuanced insights into the multifaceted relationship between voided volume, stone events, and various influencing factors within this cohort.
Conclusion
In this study, it is demonstrated that 24-hour voided volume does not exhibit a significant association with stone outcomes in a cohort of 450 nephrolithiasis patients. The subset analysis further revealed a moderate negative correlation between voided volume and stone outcomes specifically in calcium oxalate dihydrate stone formers, but not in other subgroups.
These nuanced findings suggest that the conventional guidelines recommending increased voided volume for all nephrolithiasis patients may require reevaluation. It highlights the need for a more tailored approach, identifying specific populations that might derive greater benefits from increased voided volume. This underscores the importance of advancing our understanding of the intricate relationships between voided volume, stone outcomes, and patient characteristics for more targeted and effective prevention strategies.
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