Introduction

Urolithiasis refers to stones or calculi that occur in the urinary system, such as in the kidneys, ureters, bladder or urethra, which is one of the most frequent lifetime diseases in urology.1–3 During the last few decades, the prevalence of urolithiasis has been steadily increasing worldwide and in China, and approximately 5.9% of Chinese adults suffer from it.4 Moreover, its relapse rate is high, about 50% within 5–10 years and 75% within 20 years.5 In addition to the alarming recurrent rate, the presence of urinary stones could lead to various complications, including urinary tract infection, urinary tract obstruction, chronic kidney impairment and renal failure.6–8 As one of the global health problems, urolithiasis negatively influences patients’ quality of life and imposes a substantial economic burden on families and governments.9

The aetiology of urolithiasis is complicated,8 10 and urinary stone composition is influenced by geographical location, lifestyle factors, socioeconomic conditions, anatomical deformity and some diseases.1 Clinically, exact compositional stone analysis is of significance for determining appropriate individualised treatment, understanding the underlying aetiology and conducting recurrence prevention of lithiasis.11–13 Thereby, defining stone composition should be strongly recommended for patients with urolithiasis, especially for those with a high risk of relapse.1 The guidelines of European Association of Urology (EAU) and American Urological Association likewise report that at least one analysis of stone composition should be conducted to help classify the patients and guide prevention.14 15

By literature review, there are some recent regional reports of urinary stone composition in China.1 2 8 16 However, most studies did not provide detailed data or outcomes about the influence of participants’ clinical and laboratory characteristics on stone composition, such as comorbidities, urinalysis and haematological indexes,1 8 16 preventing us from making further interpretations between stone analysis and possible predictive factors.17 Only one research evaluated the association of stone composition with patients’ sociodemographic, clinical, laboratory and environmental characteristics, which was undertaken in Tianjin city, northern region of China.2 As discussed above, geographical location is regarded as important in the influence of stone composition.1 Considering the apparent region-related variation, it is necessary to explore further the new development of stone composition among the urolithiasis population in the southern region of China, which has a high incidence of lithiasis.16 The regional focus and updated data provide valuable confirmation and potentially enhance the accuracy of understanding kidney stone composition in this particular area. Therefore, this research presented the most recent data on urinary calculi characteristics in the southern region of China and explored the effects of sociodemographic, clinical and laboratory characteristics on stone composition to fill the research gap. The research findings are estimated to supply significant evidence for understanding the underlying aetiology of urolithiasis and offer a conceptual framework for preventing and treating urinary calculi.

MethodsStudy design

A retrospective observational study was performed at the Department of Urology in one hospital in Shenzhen city, southern region of China, between December 2019 and August 2022 and was approved by the ethics committee of the institute. Records from patients over 18 years who experienced their episode of urolithiasis were collected, and those with incomplete data regarding age or gender were excluded. Finally, 858 urinary stone samples were included in the present study. All specimens were collected via spontaneous passage, shockwave lithotripsy or surgery.

All patients’ sociodemographic and clinical data were collected, including age, gender, body mass index, stone anatomical location, stone constituents, history of urolithiasis and family history of urolithiasis. The information of comorbidities comprised whether individuals were with prostatic hyperplasia, dyslipidaemia, diabetes, hypertension, kidney disease, cardiovascular disease (CVD) or cancer. The laboratory indexes included white blood cells (WBC), red blood cells (RBC), haemoglobin (HGB), platelet-to-lymphocyte count ratio (PLR), uric acid (UA), blood urea nitrogen (BUN), creatinine (Cr), albumin (ALB), total cholesterol (TC), triglyceride (TG), gamma-glutamyltransferase (GGT), nitrite, urine pondus hydrogenii (UPH, assessed by 24-hour urine samples) and urinary leucocytes (U-LEU).

Stone preparation and analysis

In line with international standards, each stone was washed with demineralised water, dried and stored in a controlled environment at 20–22°C to keep out direct sunlight and then crashed into a fine homogenised powder.2 18 The urinary stone composition was analysed by Fourier transform infrared spectroscopy (SUN-3G; Dingshun Medical Instrument Co., Ltd.; Jinan, China). Currently, this technique is regarded as the gold standard for routine calculi analysis in clinical settings because it can provide a straightforward interpretation of stone constitutes with an economical cost.19 20 Each assessment was examined by well-trained professionals and double-checked to ensure the stone analysis’s accuracy.

Stone classification

The stone was classified by the EAU guideline and the Mayo Clinic stone classification practices,19 21 such as calcium oxalate (CaOx), carbonate apatite (CA), UA, magnesium ammonium phosphate (MAP), sodium acid urate monohydrate (SA), calcium phosphate, ammonium urate (AUU), brushite and cysteine. Of which, CaOx was categorised as either CaOx dihydrate (COD) or CaOx monohydrate (COM); CA, MAP and AUU stones were belonging to infection stones.22 In the current research, calculi with a majority of >50% of a single constituent were regarded as such.23 For instance, stones were classified as CaOx or UA stones if they contained >50% of calcium oxalate, anhydrous UA or UA dihydrate. Meanwhile, stones without a main component of >50% were regarded as mixed.23 If containing any brushite or cysteine, calculi were placed in the corresponding named groups.

Statistical analysis

Numbers, percentages (%), mean, SD, median and IQR were used to describe categorical variables, continuous data with normally distributed and continuous data with non-normally distributed, respectively. Shapiro-Wilk test was used to test the normality of variables. Analysis of variance test, Kruskal-Wallis rank sum test, χ2 test and Fisher’s exact test were performed to compare sociodemographic, clinical and laboratory characteristics among different stone composition groups. Multivariate logistic regression models were conducted to evaluate the association between different characteristics and urinary stone composition and presented as OR and 95% CI. These models included known potential factors influencing stone composition, as well as significant variables in univariate analysis (P<0.05). All statistical analyses were completed by R 4.3.3 software (R Foundation, Vienna, Austria), and the level of significance was set at P<0.05 (two-sided).

Patient and public involvement

It was not appropriate or possible to involve patients or the public in the design, conduct, reporting or dissemination plans of our research.

ResultsPatients’ characteristics and stone composition

In total, 858 calculi samples from patients with urolithiasis were analysed in the study. The sociodemographic characteristics of these patients and their discrepancy among different stone composition groups are shown in table 1. The median age of these patients was 42.0 (33.0, 53.8) years, and the majority was under 60. Of these, 669 (78.0%) were collected from males, with a male-to-female ratio of 3.54:1. Comparisons of stone anatomical localisation in patients with different stone compositions are described in table 2. As shown, the majority of calculi localisation was in the upper urinary tract (815 patients, 95.0%), with 608 (70.9%) in the ureter and 207 (24.1%) in the kidney. By contrast, calculi were in the lower urinary tract in 43 patients (5.0%), with 25 (2.9%) in the bladder and 18 (2.1%) in the urethra.

Table 1

Sociodemographic characteristics of patients stratified by different stone composition groups

Table 2

Comparisons of stone anatomical localisation in patients with different stone compositions

Figure 1

The main urinary stone composition according to age (A), gender (B) and anatomical location (C). Others refer to the mixed stone, SA and brushite. CA, carbonate apatite; CaOx, calcium oxalate; MAP, magnesium ammonium phosphate; SA, sodium acid urate monohydrate; UA, uric acid.

In terms of the stone composition, almost half of the samples (424, 49.4%) were stones with a majority of >50% of a single constituent, 38.0% (316) were composed of two constitutes, and 12.6% (108) consisted of three or more components (table 1). In the present study, calculi containing CaOx dominated in the whole series, with a proportion of 80.0% (686), including 61.8% of COM (530) and 18.2% of COD (156); followed by infection stones (86, 10.0%) consisting of CA (79, 9.2%) and MAP (7, 0.8%); UA (42, 4.9%); mixed stone (42, 4.9%); SA (1, 0.1%); and brushite (1, 0.1%) (table 2).

These stone components were divided into four groups: CaOx, infection stones (CA and MAP), UA and others (mixed stone, SA and brushite). As described in table 1, table 2 and figure 1, there were significant age-, gender-, and anatomical location–related differences among the four stone composition groups (P<0.05). For instance, patients with infection stones were the youngest, with a median age of 35 years, while the ones with UA stones were the oldest, with a median age of 57. Male patients were more likely to suffer from CaOx (79.7%), while female patients were more prone to encounter other stones (36.4%). A higher proportion of CaOx (96.4%) was found in the upper urinary tract, but a higher proportion of UA stones (28.6%) was found in the lower urinary tract.

Comparisons of clinical and laboratory characteristics among patients with four stone composition groups are shown in table 3. Of the 858 patients in this study, 154 had missing or incomplete clinical or laboratory information. Thus, 704 patients were included in the analysis. According to table 3, patients with UA stones were more likely to suffer from prostatic hyperplasia, diabetes, hypertension, kidney disease and CVD; have a higher level of WBC, PLR, BUN, Cr, TG, positive nitrite and positive U-LEU; and have a lower level of RBC, ALB and urinary pH value. By contrast, individuals with CaOx were more prone to have a higher level of HGB and GGT and a lower level of PLR and positive nitrite. In addition, subjects with infection stones were more likely to have a lower level of TG and a higher level of urinary pH value. Pairwise comparisons were conducted to analyse the results further. We found that compared with the other three groups, patients with UA stone had a higher level of Cr (CaOx vs UA, P=0.004; infection vs UA, P=0.003; others vs UA, P=0.003) and BUN (CaOx vs UA, P<0.001; infection vs UA, P<0.001; others vs UA, P<0.001) and have a lower level of urinary pH value (CaOx vs UA, P=0.006; infection vs UA, P<0.001; others vs UA, P<0.001), ALB (CaOx vs UA, P=0.018; infection vs UA, P<0.011; others vs UA, P=0.007), HGB (CaOx vs UA, P=0.003; infection vs UA, P=0.032;) and RBC (CaOx vs UA, P=0.021; infection vs UA, P=0.034; others vs UA, P=0.024).

Table 3

Comparisons of clinical and laboratory characteristics among patients with different stone composition groups

Factors influencing urinary stone composition

The potential known sociodemographic, clinical and laboratory factors influencing stone composition, as well as significant variables in the univariate analysis (P<0.05), were included in the multivariate logistic analysis, and some significant factors affecting urinary stone composition are shown in table 4 (P<0.05). We found that the risk factors of patients with CaOx were increasing age (OR 1.02; 95% CI 1.01 to 1.04), male (OR 1.81; 95% CI 1.16 to 2.82), a lower level of urinary pH value (OR 0.75; 95% CI 0.58 to 0.95) and the anatomical location of upper urinary tract (OR 5.23; 95% 2.40 to 11.3), while the factors of younger age (OR 0.95; 95% CI 0.93 to 0.97), female (male OR 0.47; 95% CI 0.27 to 0.85), history of urolithiasis (OR 1.93; 95% CI 1.14 to 3.26) and a higher level of urinary pH value (OR 1.55; 95% CI 1.13 to 2.13) were identified to predict the development of infection stone significantly; and the factors of increasing age (OR 1.05; 95% CI 1.01 to 1.08), the anatomical location of lower urinary tract (upper urinary tract OR 0.12, 95% CI 0.05 to 0.34), kidney disease (OR 7.07; 95% CI 2.53 to 18.9) and a lower level of urinary pH value (OR 0.52; 95% CI 0.28 to 0.92) were evaluated to influence the development of UA stone significantly.

Table 4

Risk factors of urinary stone composition by multivariate analysis

Discussion

Owing to the high recurrent rate and various complications,4–8 urolithiasis has become one of the global public health issues, which detrimentally affects patients’ life quality and imposes a heavy burn on families and governments.9 Accurate calculi composition analysis is widely recommended and particularly critical as it can provide a basis for rational recurrence prevention, diagnosis and treatment strategies for patients with urolithiasis.14 15 China, particularly in the southern region, has a high prevalence of calculi disease.16 Thereby, the current research presents the most recent data on urinary calculi characteristics in the southern region of China and explores the effects of sociodemographic, clinical and laboratory characteristics on stone composition to fill the research gap.

First of all, we found that the majority of these patients with urolithiasis in both males and females were all under 60, which was consistent with previous studies in other areas of China1 2 and in different countries of Germany23 and the USA.18 24 The findings further identify that urolithiasis is a frequent medical disorder in the working-age population.22 25 Thus, effectively preventing urolithiasis is critical for these people in the workforce.2

Moreover, almost half of the stone samples (49.4%) in the present study were single constitute, and CaOx stone accounted for the highest proportion (80.0%), followed by infection stone (10.0%) and UA stone (4.9%). Similar studies likewise suggested that CaOx stone was the most common urinary stone component worldwide.1 16 23 26 However, we found that the prevalence of CaOx (80.0%) in Shenzhen city, the southern region of China, was higher than the incidence rate in the northern2 and central regions of China.16 The vegetarian diet and high carbohydrate intake typical in southern China may contribute to the larger proportion of CaOx stones.1 27 The possible explanation was that when these low-calcium diets were commonly used, CaOx stones could form as there was too little calcium in the intestine for oxalate to bind to. In addition, the hot climate (the average temperature of about 17.8°C) of the southern region of China could be related to a higher incidence of stones. In contrast, the cool weather (the average temperature of about 10.5°C) in the northern region of China might be associated with a low prevalence of stones.1

Some factors influencing the urinary stone composition in the current research, such as age, gender and the value of urinary pH, have been established in the previous studies. In terms of risk factors of CaOx stone, we found that CaOx increased with age (OR 1.02; 95% CI 1.01 to 1.04), which was well aligned with the prior research.8 24 In addition, males were found at higher risk of CaOx stone (OR 1.81; 95% CI 1.16 to 2.82), probably owing to a high protein diet of males that promotes a greater tendency for urine CaOx oversaturation and urinary excretion of calcium.27 Moreover, the higher androgen level of males is considered relevant, as it can stimulate urinary calcium oxalate stone formation. A lower level of urinary pH value was the other risk factor of CaOx stone (OR 0.75; 95% CI 0.58 to 0.95). A prior study suggested decreased pH may accelerate CaOx stone formation.28 Furthermore, CaOx stones were reported to occur more frequently in the anatomical location of the upper urinary tract (OR 5.23; 95% CI 2.40 to 11.3). For instance, 96.4% of CaOx stones in the study were collected from the upper urinary tract.

Regarding the factors predicting infection stones, the proportion of infection stones among females was significantly higher than that among males (male OR 0.47; 95% CI 0.27 to 0.85). Prior research also pointed out that the proportion of infection stones among women was 2–3 times that of men.16 29 It could be correlated with the anatomical characteristics of the female urethra, resulting in a higher percentage of urinary tract infections among women.30 In addition, high urine pH value (OR 1.55, 95% CI 1.13 to 2.13) and younger age (OR 0.95; 95% CI 0.93 to 0.97) were also the risk factors for infection stones, which was consistent with the previous study.2 In the current research, patients with infection stones had the highest level of urinary pH value (6.5) and had a median age of 35 years, which was the youngest (P<0.001). It needs to be noted that a history of urolithiasis was first reported as a risk factor for infection stones (OR 1.93; 95% CI 1.14 to 3.26). As described by researchers, about 20% of CaOx stone patients, when relapsed, could develop into infectious stones.2 Infection stone formation is the most severe perioperative complication for patients with urolithiasis.31 Thus, patients with a history of urolithiasis and other high-risk factors, such as females with younger age and higher urinary pH values, should be caused much more concern for appropriate individualised diagnosis and treatment strategies.

According to the multivariate longitudinal findings, we found that the incidence of UA stones improved with age (OR 1.05; 95% CI 1.01 to 1.08). The other three large calculi composition research also had similar reports.32–34 It could be due to the changes in renal function associated with ageing.35 Specifically, decreased kidney ammonia production and increased aciduria among the elderly population could lead to urine supersaturation of UA.8 It also found the anatomical location of the lower urinary tract (upper urinary tract OR 0.12, 95% 0.05 to 0.34) and kidney disease (OR 7.07; 95% CI 2.53 to 18.9) were the main risk factors for UA stones in the study. As shown in table 2, 40.0% of bladder stones were UA composition, much more frequently than other stone compositions, and bladder lithiasis was mainly caused by lower urinary tract obstruction and infection.36 The other study likewise reported that renal function was a significant factor in predicting UA stones, which are known to reflect metabolic status.34 Consistent with other research,2 16 37 a lower level of urinary pH value (OR 0.52; 95% CI 0.28 to 0.92) was evaluated to significantly promote the development of UA stone in the present study. For instance, the urinary pH value of these patients with UA stones was 5.50, which was the lowest (P<0.001). Urinary pH value is the critical determinant of UA crystallisation, as increased urine acidity can accelerate the formation of UA stone.38 Compared with other urinary stone groups, UA stones have unique treatment options, such as drug therapy; thereby, it is necessary to comprehensively analyse the characteristics of patients with UA stones.2 In the current research, these patients with UA stones exhibited apparent characteristics, such as increasing age, in the anatomical location of the lower urinary tract, having kidney disease, and a lower level of urinary pH value, which was very helpful for accurate treatment and prevention of UA stone in clinical practice.

Some limitations must be noted with the current research. First, it is a single-centre study located in Shenzhen city, and the generalisability of our findings could be diminished to the southern region of China. Future research could expand to include data from multiple cities within the region to gather a broader range of stone analysis information. Second, only patients with better financial status would be more prone to perform a calculi composition analysis; thus, our study results may be biased by patients’ socioeconomic conditions. Therefore, conducting comprehensive studies that include stone analysis for all patients with calculi in the future is deemed necessary. Third, due to the retrospective design, some factors potentially influencing stone composition, such as dietary habits, fluid intake, smoking and exercise, were not included, which were strongly recommended to explore in further research. Despite these limitations in study design, the analysis was conducted appropriately with a large amount of data.