Urolithiasis is a common disease and can reoccur at around 50% of patients within ten years, after an initial stone episode. Inflammation biomarkers including NLR, PLR, and CRP, CAR, and SIII and CAR are found to be independent indicators for the prediction of stones burden. Furthermore, there is strong association of elevated levels of NLR, derived NLR, PLR, and lymphocyte to monocyte ratio in patients with kidney stone.
A total of 399 population (patients, n = 358 and healthy controls, n = 41 patients) were include in this study. The key findings were i) Male predominance in both groups ii) The levels of lymphocyte and RDW were significantly higher in patients with kidney stones where neutrophil, PLR, NLR, SII, albumin, and CAR were comparatively higher in patients with kidney stones than the healthy controls iii) Microscopic hematuria was well-related to urinary stone disease iv) Univariate analysis and bivariate analysis showed that biochemical parameters such as neutrophil, lymphocyte, NLR and RDW were significantly associated with formation of urinary stone v) ROC analysis suggested that RDW may be useful prognostic factor for urolithiasis (P < 0.001).
Urolithiasis is most frequently seen in the adult population with a mean age of 47 (14.8) years at diagnosis [3]. Similarly, the retrospective investigation by Tang K, et al. reported prevalence of kidney stones in adult patients (52 years), which may be due to more clinical trials that have been designed exclusively for adult patients [5]. Other risk factors that attributed to the development of stones in adult patients were changes in eating habits, lifestyle, alcohol consumption, sedentary lifestyle, and obesity [10].
In a retrospective study of 513 patients with nephrolithiasis and 204 healthy controls, a significant difference was obtained in NLR, dNLR, and LMR between the patients with nephrolithiasis and healthy controls [(2.3 vs. 1.6; P < 0.001), (1.6 vs. 1.2; P < 0.001), (4.2 vs. 5.0; P < 0.001) respectively], whereas the PLR levels were comparable between both the groups (122.9 and 126.4). Significantly lowered levels of LMR was observed in patients with kidney stone [5]. In the present study, the lymphocyte level was significantly lower, while RDW level was significantly higher in patients with kidney stones. The CRP and WBC levels were comparable between patients with and without kidney stones. Neutrophil, PLR, NLR, SII, albumin, and CAR were comparatively higher in patients with kidney stones than the healthy control. A previous cross-sectional study of 11,033 patients with kidney stone from Continuous National Health and Nutrition Examination Survey (NHANES) database provided useful insights into significant association of higher CRP with a probability of having kidney stone. On the contrary, the relationship between CRP and kidney stone prevalence was not observed in the older age group patients (40 to 59 and ≥ 60 years) [11]. Oda E. investigated correlation of association of CRP and kidney stone formation (P = 0.026) [12]. However, some authors have observed that significant difference between WBC count and stone prevalence [13]. The NLR levels were significantly higher in patients with stone disease (P = 0.009). These results indicate that the presence of elevated biomarkers may have clinical importance, because the inflammatory component may contribute to developing urolithiasis.
It has been reported that elevated neutrophil increases the secretion of inflammatory biomarker mediators and thus accelerate stone formation. Moreover, elevated neutrophils provide an adequate environment for the development of kidney stones. Secondly, lower lymphocyte percentage played another significant role in stone. The presence of cytokines is generally involved in inflammatory pathways. Thus, indicates a close relationship between kidney stone and inflammatory cytokines [5]. Demiray et al. reported the association of elevated RDW with several inflammatory diseases. Higher RDW levels resulted in an increased risk of urinary stone disease due to inflammation of the uroepithelium [14]. In accordance with this, present study revealed the association of higher RDW and lower lymphocyte with stone prognosis. These findings support the conclusion that elevated levels of neutrophil, cytokine, NLR, and lower levels of lymphocyte could predict poor survival in patients with kidney stones, thus suggesting that such biomarker could play a significant role in the formation and progression of kidney stone. These observations suggest the importance of close monitoring of inflammatory biomarkers levels in patients with kidney stone. Multivariate analysis yielded a significant association of ureteral stone and microscopic hematuria. The present study also found that microscopic hematuria was well-related to urinary stone disease which is in accordance with previous study [15]. A univariate and bivariate analysis showed that biochemical parameters such as NLR and RDW were statistically related to urinary stone disease. These results are in line with a previous investigational study which showed a positive association of RDW, mean platelet volume and WBC with urinary stone disease prediction [14]. Another noteworthy literature alluded that NLR appeared to be a potentially independent useful inflammatory biomarker in patients with kidney stones, and could be useful parameter as a new inflammatory marker for monitoring disease.
Previous literature demonstrated that AUC values of NLR, dNLR, and LMR were 0.648 [95% CI: 0.604–0.692; P < 0.001], 0.625 [95%CI: (0.58–0.67); P < 0.001], 0.662 [95%CI: (0.621–0.703); P < 0.001] respectively. The AUC values of PLR could not identify patients with kidney stone from healthy controls [5]. The AUC of RDW was 0.72 (95% CI: 0.65–0.78; P < 0.001) and of mean platelet was 0.64 (95% CI 0.57–0.71; P < 0.001) [14]. This suggests that RDW was useful to diagnose patients with urolithiasis. In the present study, ROC analysis of RDW suggested an AUC of 0.78, indicating that RDW may be useful prognostic factors for urolithiasis. The ROC curve analysis suggested that CRP, WBC, lymphocyte, neutrophil, PLR, NLR, SII, albumin, and CAR had limited utility for the identification of patients with kidney stones based on AUC values.
The current study has several limitations that should be taken into consideration. Firstly, our results were from a single-centered and thus the predictive significance of systematic inflammatory biomarkers in patients with kidney stones remains to be confirmed by multicenter clinical validation studies. On the other hand, further studies need to be carried out to identify the detailed mechanisms by which cancer cells mediate inflammatory cell responses and inflammatory mediators stimulated kidney stone formation and accumulation.