(084) Low Serum Testosterone is Associated with an Increased Risk of First-time Nephrolithiasis in Men Without Testosterone Replacement Therapy
Authors: Thompson A , Rhodes S , Omil-Lima D , Obery D , Jevnikar B , Kaelber D , Thirumavalavan N 
Published: February 2024

Abstract

Introduction
Serum testosterone levels in men have declined on a population level since 1999. Although the role of testosterone in nephrolithiasis is unclear, men are twice as likely as women to develop kidney stones. Some studies posit high testosterone levels as a lithogenic factor, but a recent study showed an inverse relationship between testosterone levels and kidney stones, suggesting that low testosterone may increase the risk of kidney stones in men over 40. The relationship between low testosterone in men and kidney stone risk remains unclear.

Objective
To determine the association of low serum testosterone levels with the development of incident kidney stones in men without a history of testosterone therapy (TTh).

Methods
Using TriNetX, a tool that de-identifies and aggregates electronic health record data from tens of millions of patients, we used the TriNetX Research Network to examine men aged ≥18 with a known testosterone level. Men with a history of nephrolithiasis before testosterone measurement and a history of TTh at any point in their life were excluded as both are known to increase the risk of subsequent kidney stones. Men were divided into a low testosterone group (&lt;300 ng/dL) and a normal testosterone group (300-1000 ng/dL). Demographic and clinical characteristics, including comorbidities and medications, were compared using descriptive statistics for all patients. To address potential confounders, we used propensity score matching based on demographic and clinical characteristics (Table 1). We used 1:1 greedy nearest-neighbor matching with a caliper of 0.1 pooled standard deviations of the propensity score. A standardized mean difference of less than 0.1 indicated successful matching. Our outcome of interest was all-time risk of developing an initial kidney stone in men aged ≥18 following a laboratory-confirmed low testosterone. Subgroup analyses was performed on age cohorts. Survival analysis was performed using a log-rank test and Cox proportional hazards regression. All analyses were performed on the TriNetX platform without natural language processing.

Results
445,682 men ≥18 with low testosterone were included. The number of men before matching (Table 1) and in each age subgroup after matching is seen in table 2. The percentage of men that developed a diagnosis of nephrolithiasis increased with age regardless of testosterone level (Table 2). In men ≥18, low testosterone was associated with higher risk of incident nephrolithiasis (HR 1.14, 1.11-1.17). Men with low testosterone aged 34-44 (HR 1.28, 1.18-1.40) had the highest risk of nephrolithiasis. Low testosterone was not associated with an increased risk of nephrolithiasis in men aged 18-24 (Figure 1).

Conclusions
In investigating the association of low testosterone with kidney stones in men without a history of kidney stones or TTh, we found that low serum testosterone is associated with a higher risk of a first-time encounter diagnosis of nephrolithiasis in men greater than 25 years of age compared to men with normal testosterone levels. Men aged 33-44 with low serum testosterone had the highest risk of nephrolithiasis. Future work will investigate the risk of kidney stone recurrence in men with low serum testosterone levels.

Disclosure
No.