Associations between multiple inflammatory biomarkers and the risk of developing kidney stones

Nephrolithiasis, with a prevalence of 9% and increasing worldwide, has a recurrence rate close to 50%. Urinary stones significantly impact quality of life and impose substantial economic burdens on patients and healthcare systems. Systemic inflammation is postulated as a risk factor for urinary stones. Previous studies have identified associations between inflammatory markers and kidney stones, but these often rely on patient recall, introducing potential recall bias. This study investigates whether inflammatory markers vary according to the presence of nephrolithiasis using health check-up data from a large cohort in South Korea.

Data were collected from participants in health checkups at a university hospital in Seoul between 2010 and 2020. The study included 18,243 males and 12,919 females who underwent blood tests, KUB (Kidneys, Ureters, and Bladder) radiography, and ultrasound examinations. Only stones larger than 5 mm were counted, enrolling 328 males and 99 females with kidney stones. Exclusion criteria included pyuria, congenital renal deformities, renal cancer, kidney transplant, and diuretic use. Inflammatory markers assessed included the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammatory index (SII). The primary outcome was the presence of nephrolithiasis, detected using combined ultrasonography and KUB radiography. Logistic regression analyses determined the association between inflammatory markers and nephrolithiasis, adjusting for confounders such as age, BMI, blood pressure, triglycerides, LDL, HDL, creatinine, BUN, uric acid, fasting glucose, calcium, and medical history.

In females, an LMR ≤ 5.02 (OR: 2.30, 95% CI: 1.47-3.61, p < 0.001), NLR > 1.94 (OR: 1.97, 95% CI: 1.24-3.12, p = 0.004), and SII > 484.05 (OR: 2.12, 95% CI: 1.38-3.24, p < 0.001) were significantly associated with kidney stones after adjusting for confounders. In males, an LMR ≤ 7.79 (OR: 1.82, 95% CI: 1.33-2.49, p < 0.001) and NLR > 1.32 (OR: 1.55, 95% CI: 1.12-2.15, p = 0.009) were significantly associated with kidney stones, but SII > 560.11 was not (OR: 1.21, 95% CI: 0.87-1.68, p = 0.255), after adjusting. The significant relationships between these inflammatory markers and kidney stones were maintained only in participants aged ≥ 50 years. Specifically, in females aged ≥ 50 years, LMR ≤ 5.02 (OR: 2.38, 95% CI: 1.52-3.74, p < 0.001), NLR > 1.94 (OR: 2.05, 95% CI: 1.30-3.24, p = 0.002), and SII > 484.05 (OR: 2.18, 95% CI: 1.43-3.32, p < 0.001) were significant predictors of nephrolithiasis. In males aged ≥ 50 years, LMR ≤ 7.79 (OR: 1.90, 95% CI: 1.38-2.62, p < 0.001) and NLR > 1.32 (OR: 1.62, 95% CI: 1.17-2.25, p = 0.004) were significant predictors.

Elevated inflammatory markers are significantly associated with the presence of kidney stones, particularly in individuals aged 50 years or older. These findings suggest that systemic inflammation plays a crucial role in the pathogenesis of nephrolithiasis, especially in the older population. The results imply that inflammation contributes to the increasing prevalence of urinary stones with age, highlighting the importance of managing systemic inflammation in preventing nephrolithiasis. Future research would be needed to explore causal relationships and investigate whether anti-inflammatory interventions can reduce the risk of kidney stones.