With the change in living habits, and the improvement of imaging technology, the incidence and prevalence of urolithiasis are increasing. Particularly, bilateral urinary stones pose a considerable challenge to clinicians12. Bilateral urinary tract stones affect the urinary tract's patency, thereby affecting the change of the internal urine environment and the damage of kidney function11. Therefore, for patients with bilateral kidney stones, early detection will not only help clinicians formulate the best treatment plan, but also help patients prevent the recurrence of kidney stones.
In this study, 34.3% of all patients with kidney stones were diagnosed with bilateral kidney stones, which was higher than previous reports13. Such an increase may be attributed to the changes in people's living habits and the increasing incidence of metabolic diseases in recent years. Our research indicates that compared with patients with normal metabolism, patients with metabolic-related diseases have a higher incidence of bilateral kidney stones. The multivariate analysis results and univariate analysis indicated that BMI, history of kidney stones, history of diabetes, history of hypertension, history of gout, and the maximal stone diameter are independent risk factors for forming bilateral kidney stones. Among the patients with bilateral kidney stones, there were 1937 (25.5%) obese patients (BMI ≥ 24kg/m2), 795 (10.5%) patients with hypertension, and 470 (6.2%) patients with diabetes. According to previous research reports, the incidence of metabolic syndrome and urinary tract stones is significantly positively correlated8,14. Metabolic syndrome includes hypertension, insulin resistance, obesity, and dyslipidemia. The definition of metabolic syndrome varies according to different standards. The internationally recognized threshold value of the American Diabetes Association IDF standard (by race and gender) is that the three or more following terms are met: (1) Fasting triglyceride content is 150mg/dL and above; (2) Systolic blood pressure is 130mmHg and above, and or diastolic blood pressure is 85mmHg and above; (3) Fasting blood glucose content is 100mg/dL and above; (4) High-density lipoprotein (HDL) is 40mg/dL and below for men and 50mg/dL and below for women; (5) Waist circumference: 90cm and above for men and 80cm and above for women15. Although many studies have confirmed that metabolic syndrome can promote the onset of urinary calculi in recent years, this study initially confirmed that metabolic syndrome is significantly positively correlated with the onset of bilateral kidney stones. Besides, this study also explored the correlation between the affected side of kidney stones and the number of stones, and the study results showed that the two were not statistically significant.
BMI can well represent the relationship between weight and height, and BMI can also reflect the state of fat storage. Our research demonstrates that the average BMI of patients with bilateral kidney stones (26.23 ± 3.53kg/m2) is significantly higher than that of patients with unilateral kidney stones (25.82 ± 3.52kg/m2). This is consistent with reports written by Milicevic, S et al. and Scales CD Jr et al.1,7. That is, obesity, overweight, and kidney stones are related, and as BMI increases, urinary calcium and uric acid excretion increases, and the incidence and recurrence rate of urolithiasis are also rising. Antonelli, J A reported that compared with the average human, the incidence of urolithiasis in obese and overweight patients was as high as 75%16. This may be the same reason why patients with higher BMI often formulate bilateral kidney stones. Therefore, patients can reduce the incidence of urolithiasis by adjusting diet, strengthening exercise, and lowering BMI.
Kabeya, Y, and Weinberg, A E reported that kidney stones' incidence and recurrence rate were significantly higher in patients with than without DM17,18. The study by Devasia, D et al. reported that in patients with diabetes and urinary calculi, serum adiponectin levels and the content of calcium and phosphate in urine were significantly higher than those in patients with diabetes without urinary calculi19. Our research results show that compared with non-diabetic patients, diabetic patients are more likely to develop bilateral kidney stones. The reason may be related to two underlying mechanisms: one is that in insulin-resistant diabetic patients, due to the change of uric acid clearance rate, acid urine is often produced, and long-term changes in the internal environment of urine can promote the formation of uric acid stones20; The other is that diabetic patients are significantly higher than non-diabetic patients in terms of gastrointestinal absorption of oxalate and endogenous metabolism to produce oxalate21.
Hypertension can increase the reabsorption of water, sodium, and calcium by the kidneys, leading to multiple atherosclerosis in the kidneys, which significantly increases the risk of calcium stones and uric acid stones. Our study results show that patients with a history of hypertension have a significantly higher incidence of bilateral kidney stones. This is consistent with the reports of Kohjimoto Y et al. and Cappuccio FP et al.: Compared with normal people, patients with hypertension have a significantly increased risk of kidney stones22,23. Therefore, patients can effectively control high blood pressure and prevent calcium stone formation through a low-sodium diet and eating more fruits and vegetables. Recent studies have reported that thiazide diuretics can effectively relieve hypertension and prevent stones' formation for patients with ineffective dietary adjustments24.
In summary, we speculate that metabolic-related diseases, especially metabolic syndrome, may be an independent risk factor for bilateral kidney stones, and the reason is related to changes in urine composition. Research by Cho, ST et al. reported: Compared with patients without MetS, urine PH, citrate, uric acid, and calcium in patients with MetS were significantly lower, while the content of uric acid in the blood was significantly increased. Patients with one characteristic of MetS have a risk of stones of 10.2%, and those with four characteristics of MetS have a risk of stones of 30.4%25. Although our study did not further clarify whether the superposition of various metabolic factors will further promote the onset of bilateral urinary tract stones, it preliminarily confirmed the correlation between MetS and bilateral urinary tract stones.
Gout is one of the important complications of hyperuricemia. Our results show that the proportion of bilateral kidney stones is 58.2% in all patients with gout and kidney stones. This is consistent with reports by Shimizu, T: About 34% of gout patients have urinary tract stones, and more than 50% of them have bilateral urinary tract stones11. Due to the low pH value of urine in patients with gout, the solubility of uric acid crystals in urine is low, and uric acid precipitates in the urinary tract to form stones26. Another generally accepted explanation is that in the urine of patients with gout, uric acid crystals are used as the core to form heterogeneous nucleation with uric acid crystals as the core, and the urate and oxalate crystals grow epitaxially, thereby forming mixed urinary tract stones27. We believe that these mechanisms may also promote the formation of bilateral urinary tract stones.
Regarding the correlation between the past history of kidney stones and bilateral kidney stones, our research results show that the first kidney stones found are more common in unilateral kidney stones, while patients with recurrent kidney stones are more common in bilateral kidney stones. The reasons may be related to lifestyle habits such as low water intake, a high purine diet, and taking particular drugs26,28. If these habits contributing to kidney stones' pathogenesis are not effectively corrected, it may lead to the formation of bilateral kidney stones.
Additionally, our research also found that the stones' diameter is positively correlated with the incidence of bilateral kidney stones. Previous studies by Wen JG et al. reported that the maximum diameter of stones is related to renal failure, resulting in decreased renal excretion of uric acid and calcium29. To a certain extent, this can explain our research results. Simultaneously, the maximal diameter of a stone is positively correlated with the stone's duration, and these factors may promote the formation of bilateral kidney stones. We also compared the relationship between the stone affected side (left/right) and the number of stones (single/multiple), but the study results showed no significant correlation between the two. At present, there are few reports on related studies between the two, and a large randomized controlled study is still needed for further demonstration.
The shortcomings of this study: First of all, as to whether the stone composition is related to the formation of bilateral kidney stones, relevant data collection and statistical analysis were not carried out; Secondly, because the content of uric acid and blood lipids is a dynamic process, and the content of both is also related to the patient's recent diet and drug control, it is impossible to obtain an optimal predictive value for the formation of bilateral kidney stones; Third, due to the diversity of Chinese people's dietary habits and the diversity of medications for chronic diseases, the data on dietary habits and medications have not been collected and included for analysis.