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. 2025 Aug 9;25(1):193.
doi: 10.1186/s12894-025-01878-5.

The association between urinary nitrate and prostate specific antigen without prostatic disease: a cohort study

Zhiyi Chen  1 , Enpu Zhang  1 , Lu Gan  1 , Wenjuan Zhang  1 , Guixiao Huang  2
Affiliations

The association between urinary nitrate and prostate specific antigen without prostatic disease: a cohort study

Zhiyi Chen et al. BMC Urol. .

Abstract

Purpose: The carcinogenic effects of nitrate reduction to nitrite are well established, and nitrate has been closely linked to various diseases. However, research on its effects on the urinary system remains limited, and its association with PSA remains unclear. This study aims to investigate the relationship between urinary nitrate and PSA.

Methods: We employed weighted generalized linear models, weighted univariate analysis, forest plots, weighted multivariable analysis, and generalized additive models (GAM) to investigate the relationship between urinary nitrate and PSA. Subgroup analyses were conducted to further validate the stability of this association across different groups. GAM was utilized to provide a more intuitive representation of the specific relationships between PSA and urinary nitrate.

Results: TPSA, FPSA, and the prostate specific antigen ratio (%, 4 ng/mL ≤ TPSA ≤ 10 ng/mL) showed negative correlations with urinary nitrate. After adjusting for confounders, only the prostate-specific antigen ratio maintained a significant negative association (β = -632.7; 95% CI: -1094.9, -170.6; P = 0.011), while correlations with TPSA and FPSA were not statistically significant. A nonlinear relationship was observed, where urinary nitrate initially remained stable or changed minimally before gradually declining.

Conclusion: This study identifies a negative correlation between urinary nitrate and the prostate-specific antigen ratio in individuals with gray-zone TPSA. These findings enhance our understanding of urinary nitrate's impact and may help reduce overtreatment in this population.

Keywords: NHANES; PCa; PSA; Urinary nitrate.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted by following the Declaration of Helsinki, and the National Center for Health Statistics institutional review board approved the overall NHANES. This study was approved by the Institutional Review Board and documented consent was obtained from participants. Clinical trial number: not applicable. Competing interests: The authors declare no competing interests. Informed consent: The survey protocol was approved by the Research Ethics Review Board of the National Center for Health Statistics ( https://www.cdc.gov/nchs/nhanes/ ), and NHANES has obtained written informed consent from all participants.

Figures

Fig. 1
Fig. 1
Flow chart of the study population. NHANES the National Health and Nutrition Examination Survey
Fig. 2
Fig. 2
Effects on the correlation between TPSA and urinary nitrate in different subgroups
Fig. 3
Fig. 3
Effects on the association between prostate-specific antigen ratio (%, 4 ng/mL ≤ TPSA ≤ 10 ng/mL)and urinary nitrate in different subgroups
Figs. 4
Figs. 4
Association between PSA and Urinary nitrate. The Solid red line represents the smooth curve fit between variables. Blue bands represent the 95% confidence interval from the fit. A A linear association between TPSA and Urinary nitrate was found in a generalized additive model (GAM). The results were obtained after adjusting for Age; Race (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Other Race); Education level (High School Grad and Less Than and Above); BMI (≥ 25 kg/m2,<30 kg/m2 and ≥ 30 kg/m2); CRP; Diabetes (No, Yes); Hypertension(No, Yes); Serum cotinine(≤ 10ng/mL,>10ng/mL); Urinary creatinine (mg/dL); Drinking (No, Yes). It can be seen that after adjusting the relevant variables, TPSA was linearly correlated with Urinary nitrate, and Urinary nitrate decreased with the increase of TPSA. B The results were obtained after adjusting for Age; Race (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Other Race); Education level (High School Grad and Less Than and Above); BMI (≥ 25 kg/m2,<30 kg/m2 and ≥ 30 kg/m2); CRP; Diabetes (No, Yes); Hypertension(No, Yes); Serum cotinine (≤ 10ng/mL,>10ng/mL); Urinary creatinine (mg/dL); Drinking (No, Yes). FPSA and urinary nitrate exhibit a negative but nonlinear correlation, wherein urinary nitrate levels decrease with increasing FPSA; however, the rate of decline gradually diminishes. C Association between Prostate specific antigen ratio (%, 4ng/mL ≤ TPSA ≤ 10ng/mL) and Urinary nitrate
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