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Kidney stone disease (KSD) is a major public health concern associated with high morbidity and recurrence, places a significant burden on the health care system worldwide. Calcium oxalate (CaOx) alone or a mixture of CaOx and calcium phosphate stones accounting for more than 80 % of cases. However, beyond surgical removal, the prevention and reduction of recurrence of CaOx kidney stones have always been a challenge. Given that macrophages are traditional innate immune cells that play critical roles in the clearance of pathogens and the maintenance of tissue homeostasis, which have gained more and more interests in nephrolithiasis. Several studies recently clearly demonstrated that M2-macrophage could reduce the renal calcium oxalate (CaOx) crystal acumination, and provide premise insights and therapeutic options for KSD by modulating the macrophage phenotypes. However, the mechanism of macrophage-polarization regulation and that effects on kidney stone prevention and treatments are far from clear. Here, we comprehensively reviewed the literatures related to cytokines, epigenetic modifications and metabolic reprograming of macrophage in CaOx kidney stone disease, aimed to provide better understandings on macrophage polarization regulation as well as its potential clinical applications in CaOx kidney stone disease treatments and prevention., Competing Interests: Declaration of Competing Interest The authors declare that the results as reported in this manuscript are original and have not been published previously or accepted for publication elsewhere, and also not under consideration for publication elsewhere. All authors have seen and approved its publication. We also declare that there is no financial conflict of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function., Methods: Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group., Results: Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups., Conclusions: Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore., (© 2024. The Author(s).)

Purpose: Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis., Methods: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results., Results: After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93-0.98, p-value = 7.20 × 10 - 4 , q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05., Conclusions: Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies., (© 2024. The Author(s).)