Understanding the influence of demographic and clinical factors on urinary stone composition: A retrospective multivariate study in a diverse population

Abstract

Background: Demographic and clinical factors significantly influence urinary stone composition; however, data from other Arabian Gulf countries still lack further exploration of these variables with the aid of multivariate analyses. This study aims to address this gap by conducting an in-depth multivariate analysis of the demographic and clinical variables associated with different urinary stone compositions.

Methods: A retrospective analysis of data from 1193 patients' charts between January 2017 and February 2019. Demographic, clinical data, and stone characteristics were recorded. Statistical analyses included one-way analysis of variance, Pearson's chi-square, and multinomial logistic regression to identify factors associated with different stone compositions.

Results: A total of 1193 patients were analyzed (male:female ratio = 8:1, mean age = 42.53 ± 11.31 years, mean body mass index (BMI) = 28.22 ± 5.23 kg/m²). Calcium oxalate (CaOx) was the most common stone type (87.7%), followed by uric acid (UA) stones (9.13%). CaOx was predominant across all ethnicities. Patients with CaOx stone were younger than patients with UA and other stone types. BMI was significantly higher in the UA group. UA stone formers were more likely to have hypertension, chronic kidney disease (CKD), and recurrent urolithiasis than CaOx patients. Multinomial logistic regression identified UA stones as significantly associated with older East Asians, higher BMI, recurrent stone formation, and lower baseline glomerular filtration rate compared to CaOx.

Conclusion: CaOx was the most prevalent stone type, whereas UA stones were more commonly observed in patients with higher BMI, CKD, older age, and a history of recurrent urolithiasis. These differences highlight the importance of targeted prevention and personalized management strategies.

Keywords

nephrolithiasis / Qatar / stone composition / urinary stone

1 INTRODUCTION

Urolithiasis affects 1%–13% of the global population, with rising incidence due to improved diagnostics[1,2]. The European Society of Urology classifies stones into calcium oxalate (CaOx), uric acid (UA), and other less common types[3]. Identifying stone composition and its correlates is crucial for effective prevention and management[4,5]. Demographic, clinical, and environmental factors play a role in stone formation. Epidemiological studies have shown that age, sex, some systemic diseases, body mass index (BMI), and ethnicity are correlated with the composition of the stones[6].

Patient demographics significantly influence stone composition. Although CaOx is the most common stone type across all age groups, young females have a higher prevalence of infection stones, and UA stone prevalence increases with age in both sexes[7]. Ethnicity also plays a role, as studies in the United States and the United Kingdom have reported associations between ethnicity and stone composition[8,9], though findings in South Africa did not confirm this correlation[10]. Geographic factors further influence stone risk, with variations in urine calcium, phosphate, and urate levels observed across different regions of the United States, independently of temperature[11]. Similarly, a high prevalence of urolithiasis with CaOx predominance has been reported across the Arabian Gulf States[12].

Systemic diseases such as type 2 diabetes mellitus (T2DM), hypertension (HTN), metabolic syndrome, and chronic kidney disease (CKD) are strongly linked to nephrolithiasis. Diabetics have a twofold increased risk, with UA and CaOx stones being the most common types, particularly UA, due to its lower urinary pH [13,14]. HTN has a bidirectional relationship with nephrolithiasis, with stone formers at higher risk of HTN and vice versa[15]. Although some studies associate HTN with UA stones[16], others suggest a higher risk of CaOx stones[17]. Obesity is another independent risk factor, increasing stone formation and recurrence rates[18]. Though the link between BMI and CaOx stones remains inconsistent, obesity is associated with hyperuricosuria and a higher risk of UA stones, likely due to high carbohydrate and protein intake[19].

Our study is a countrywide analysis of all stones submitted to Qatar's specialized stone analysis laboratory, aiming to evaluate demographic and clinical factors independently associated with different urinary stone compositions. We assess the relationships between stone composition and variables such as age, BMI, ethnicity, and comorbidities, employing regression analysis to identify independent predictors of stone composition.

2 METHODS

2.1 Settings

Our institution is the largest referral tertiary care facility in the country, with a state-of-the-art Stone Centre, and receives almost all cases of urolithiasis across the country. Qatar's considerable expat populations provide an excellent opportunity to appraise the relationships between ethnicity and stone composition.

2.2 Ethics

The retrospective chart review was approved by our institute's ethics committee (MRC-01-19-319), and a waiver of signed informed consent was obtained. Using the databases of the Stone Centre, the chart review was conducted at the Department of Urology of Hamad Medical Corporation between January 2017 and February 2019.

2.3 Population

The data were collected from stone analysis results and charts. These stones were collected from patients who spontaneously passed stones and brought them during their clinic appointments, patients who passed stones after extracorporeal shock wave lithotripsy and handed the stones in their follow-up appointments, stones extracted surgically during ureteroscopy, retrograde intrarenal surgery, or percutaneous nephrolithotomy. Patients with urolithiasis without stone analysis were excluded. A total of 1193 patients' records met the inclusion criteria.

2.4 Procedures and data collection

Patients' electronic medical records were screened for clinical and demographic information including age, sex, BMI, ethnicity, comorbidities (T2DM, HTN, and CKD), glomerular filtration rate (GFR), plasma UA level, and history of urolithiasis to identify recurrent stone formers. Stone characteristics including stone composition and Hounsfield unit (HU) were also retrieved. T2DM was defined based on a prior diagnosis or documented use of antidiabetic medication[20]. HTN was recorded if patients had a history of HTN or were on antihypertensive therapy[21]. CKD was classified according to the kidney disease: Improving Global Outcomes guidelines, with CKD defined as an estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m² (Stages 3–5)[22].

2.5 Stone analysis

Stones were analyzed in a specialized stone laboratory at our facility using Fourier-transform infrared spectroscopy. Each stone was weighted, then a representative sample of the stone was crushed into powder, and an infrared spectrum was obtained. The spectrum was compared to a reference spectrum of a known stone chemical component, such as calcium, oxalate, UA, or cystine, allowing precise analysis of the mixed crystals[23]. Stones were classified according to the European Urology Association into CaOx monohydrate or dihydrate; calcium phosphate (if > 50% was carbapatite, or amorphous calcium phosphate); UA; and mixed UA stones (if UA component is > 30%)[3,24]. All other types were categorized as other stones including struvite stone, matrix stone, cystine, and xanthine.

2.6 Statistical analysis

Statistical analyses were undertaken using the statistical package SPSS 20.0. Differences in descriptive continuous variables between groups were tested by a one-way analysis of variance (ANOVA). Tukey's post hoc testing for ANOVA was undertaken for continuous variables. Homogeneity of variance was tested using Levene's test. In cases where Levene's test was significant, the results of Welch ANOVA (robust test of equality of means) and post hoc Games–Howell were reported instead. Differences in descriptive categorical variables between groups were tested using Pearson chi-square, and post hoc testing was undertaken by transforming the adjusted residuals for each cell from the crosstabulation table and comparing to a Bonferroni corrected alpha[25,26].

For the analyses, stones were classified into CaOx (included CaOx mono and dehydrate); UA (including mixed UA stones); and “other” stones that included cystine, matrix, xanthin, struvite, brushite, and hydroxyapatite. Because of the multinational expatriate population of Qatar, the observed nationalities were grouped geographically into six categories (Qatari + Gulf Cooperation Council (GCC) states, Arab (non-GCC), Indian subcontinent, East Asia, Europe + North America, and Africa).

A multivariable multinomial logistic regression model identified significant associations of the variables under examination with either UA or other stones compared to CaOx as the reference group. The model used a backward elimination approach, which included all variables up front into one model, then eliminated nonsignificant variables from the model to result in the final model of significant predictor variables. Backward elimination was chosen to avoid the unintentional elimination of important predictor variables that may not be initially significant using a forward selection or stepwise approach.

3 RESULTS

3.1 Demographic characteristics

Table 1 presents the demographic characteristics stratified by stone composition. The overall mean age of the cohort was 42.53 ± 11.31 years. When analyzed by stone type, the mean ages were 41.98 ± 11.10 years for CaOx, 48.89 ± 10.64 years for UA, and 38.16 ± 14.10 years for other stone types.

Pertaining to sex, the overall male-to-female ratio was 8:1, although CaOx was the most common stone type encountered among both sexes. Post hoc testing of demographic characteristics found significantly less females and more males in the CaOx group and significantly more females and less males in the “other” stones group (data not presented).

Regarding ethnicity, almost half the sample were Indian subcontinent patients, followed by non-Qatari Arab nationalities, and Qataris (49.79%, 31.07%, and 12.17%, respectively). CaOx was a predominant composition among all ethnicities. Post hoc testing found significantly less East Asians represented in the CaOx group, and significantly more East Asians represented in the “other” stones group compared to other ethnicities (data not presented).

Mean BMI was 28.22 ± 5.23 kg/m² and was significantly higher among patients presenting with UA compared to those with CaOx stones.

3.2 Characteristics of stone composition

A total of 1193 patients had urinary stone analysis during the study period and were included. Table 2 depicts the distribution of their stone composition. CaOx was predominant, comprising 87.7% of the stones, among which CaOx monohydrate was more common (41%) than dihydrate (34.2%). UA stones were the second most common type with a prevalence of 9.13%. All other stone types accounted for < 1% each.

3.3 Clinical characteristics

Table 3 shows the baseline clinical characteristics by stone composition. CKD (16.43%) was the most common comorbidity, followed by HTN (13.59%) and T2DM (7.55%). There were no significant differences in the prevalence of T2DM by stone type; however, post hoc testing found more patients with HTN and CKD in the UA stones group.

Patients with UA stones displayed significantly higher baseline creatinine compared to those with CaOx or “other” stone types (89.80 ± 29.21, 79.52 ± 17.71, 68.33 ± 22.75 µmol/L, respectively). This was also reflected in the significantly lower GFR among the UA group (p = 0.019) compared to the CaOx and “other” stone groups. Recurrence was significantly higher among patients with UA stones (p < 0.001) and significantly lower among those with CaOx stones, as patients with CaOx stones generally had a single urolithiasis episode.

3.4 Demographic and clinical characteristics independently associated with stone composition

Table 4 shows the regression of demographic and clinical characteristics on stone composition, while controlling for the other variables under examination. Patients with UA stones were significantly more likely (i.e., higher odds) than those with CaOx to be older, have a higher BMI, be of East Asian descent, and have had recurrent stone episodes. Additionally, they were also significantly more likely to have lower baseline GFR. There was no sex difference between patients with UA versus CaOx stones.

On the other hand, patients with “other” stone compositions, compared to those with CaOx stones, were significantly more likely (higher odds) to be females and East Asian. There were no differences in age, BMI, T2DM, recurrence episodes, or GFR between patients with “other” stone compositions versus those with CaOx.

Through the backward elimination process of the regression, baseline creatinine, HTN, CKD, and ethnicity variables (Qatari, Indian subcontinent, and non-Qatari Arab) were removed as being not significant to stone composition.

4 DISCUSSION

The etiology and pathogenesis of urolithiasis are multifactorial, as multiple elements contribute to the process of stone formation[27]. Studies have reported possible associations between the environmental, geographical, and clinical factors and urolithiasis in the Gulf and Middle East regions[12,28–33]. Nevertheless, most of these studies suffered limitations. To improve our understanding of the range of factors associated with different stone compositions in locations with a high prevalence of urolithiasis, for example, the Arabian Gulf Region, we retrieved data on the stones from the main Stone Referral Centre in Qatar and evaluated these associations using multivariate methods.

Ethnicity is closely linked to geography, yet most research has focused on stone incidence rather than composition, with findings on ethnicity–stone composition relationships remaining inconsistent. Although studies in the United States and United Kingdom have reported associations between ethnicity and stone composition[8,9], research in South Africa failed to establish a direct correlation[10]. Geographic location has also been shown to influence urinary biochemical parameters, such as calcium, phosphate, and urate levels, independent of climate[11]. Across the Arabian Gulf States, a high prevalence of urolithiasis with CaOx predominance has been documented[12].

Urolithiasis is widespread in the Arabian Gulf, attributed to the region's multiethnic population, hot climate, and high humidity[12]. However, studies examining stone composition in these countries have several limitations, including limited geographical distribution (mostly from Saudi Arabia)[28–33], small sample sizes[31,34], and a lack of nationally representative data[29,30,32]. Furthermore, only one study explored the ethnicity–stone composition relationship, categorizing patients into a crude Saudi/non-Saudi classification[29]. Most studies relied on descriptive or correlation analyses without adjusting for confounders, and regression analysis for independent predictors of stone composition remains largely unexamined[28].

Qatar's uniquely diverse expatriate population provides a valuable opportunity to study ethnic differences in stone composition. Our study found that urolithiasis was most prevalent among patients from the Indian subcontinent, followed by Arabs (p < 0.001), consistent with findings in London, where South Asian immigrants exhibited higher stone prevalence[35]. Given that South Asians already have the highest urolithiasis rates in Asia[19], the similar patterns observed in Qatar and London[35] raise questions about whether immigrants retain their native predisposition for stone disease. However, this conclusion cannot be reached in a retrospective design, considerating the dietary, occupational, and environmental alterations in their current locations, in addition to the missing information on the mean duration of stay of these expatriates. All of these factors necessitate a prospective exploration.

The higher prevalence among South Asians and Arabs is likely multifactorial, influenced by dietary habits, with high-protein diets linked to stone formation in both India[36] and the Middle East[12]. Additionally, occupational factors may contribute, as many South Asian and Arab males in Qatar are engaged in manual labor, which exposes them to heat stress and dehydration, the key risk factors for stone formation[37,38].

Regarding stone composition, CaOx was the most common type across all ethnicities. However, CaOx stones were significantly more frequent among African and Indian subcontinent patients compared to East Asians (100%, 90.2%, and 68%, respectively; p < 0.001). Conversely, UA stones were more prevalent among East Asian and European populations (18.5% and 15.8%, respectively; p < 0.001). These findings align with reports from London, where CaOx stones were predominant among Asians and Africans, whereas British and European patients exhibited a higher prevalence of UA stones[9]. This suggests that ethnic and regional factors play a crucial role in stone composition, reinforcing the need for tailored prevention strategies based on demographic and lifestyle factors.

Systemic diseases such as T2DM, HTN, metabolic syndrome, and CKD are strongly associated with nephrolithiasis. Diabetics have a twofold increased risk, correlated with disease severity, and are more prone to UA and CaOx stones, particularly UA due to lower urinary pH [13,14,39]. HTN has a bidirectional relationship with nephrolithiasis, increasing the risk of stone formation and vice versa[15]. Although some studies associate HTN with UA stones[16], others suggest a higher risk of CaOx stones[17]. Obesity is an independent risk factor, increasing stone formation and recurrence rates[18], with hyperuricosuria and a higher risk of UA stones linked to high carbohydrate and protein intake[19].

In our study, post hoc analysis revealed a higher prevalence of HTN and CKD in UA stone formers, consistent with evidence linking these conditions to nephrolithiasis and metabolic syndrome[13,16,40,41]. Regression analysis confirmed that UA stone patients had significantly lower GFR than those with CaOx stones, supporting prior findings that UA supersaturation increases with declining renal function, whereas calcium-containing stones exhibit reduced supersaturation at lower GFR levels[42].

Similarly, obesity (higher BMI) was more common in UA stone formers. Regression analysis confirms a significant association between obesity and UA stone formations, which aligns with the literature attributing this to urine biochemical alterations, lower pH, and higher UA levels[13,43–46]. However, we found no significant association between diabetes and UA stones, despite previous reports[47], likely due to the relatively low prevalence of diabetes (7.55%) in our study population.

Stone recurrence in relation to stone composition was noted in the literature, albeit with conflicting results. Although some authors view that stone type alone is insufficient to determine the recurrence potential, and that stone morphology is an important factor[48], a systematic review found that UA stones are associated with a higher recurrence rate[49]. We are in agreement, as we noted that recurrence was significantly higher than expected among patients with UA stones (p < 0.001) and significantly lower than expected among those with CaOx stones. This indicates that those with CaOx stones generally had a single episode of urolithiasis.

This study has several limitations. As a retrospective analysis, it is subject to inherent biases, including potential inconsistencies in data collection and missing information. Additionally, the small representation of certain ethnic groups, such as Africans and Europeans, limits the generalizability of our findings to these populations. Although our regression model identified significant predictors of stone composition, the relatively small number of cases in the “other stones” category may have reduced the statistical power to detect meaningful associations within this group.

Furthermore, despite our study's broad inclusion criteria, the expatriate-dominated population structure in Qatar may not fully represent global urolithiasis patterns. Environmental and lifestyle factors, such as dietary habits and occupational exposure, could differ across regions and may not be entirely accounted for in our analysis. Future studies should consider larger, multicenter cohorts with more balanced ethnic representation to validate our findings and further investigate the complex interplay among ethnicity, clinical factors, and stone composition. Prospective studies with standardized data collection and long-term follow-up could also help establish causal relationships and refine preventive strategies tailored to diverse populations.

To our knowledge, this is one of the few studies to undertake an in-depth multivariate analysis of the demographic and clinical variables independently associated with the different compositions of urinary tract stones across the Arabian Gulf region. Such findings would be important to guide the prevention of urolithiasis. When combined with other clinical diagnostic modalities, they will help in the diagnosis and treatment of urinary tract stones, leading to more favorable patient outcomes and quality of life.

5 CONCLUSION

The multiethnic composition of Qatar's population contributes to variations in stone composition, recurrence rates, and associated risk factors. Our findings emphasize the influence of demographic and clinical variables, including age, BMI, comorbidities, and ethnicity, on stone formation. Given these differences, targeted public health initiatives, such as media campaigns and community education, are essential to raise awareness about nephrolithiasis. Additionally, personalized counseling for stone formers is recommended to address variations in dietary habits, educational backgrounds, and genetic predisposition. This study provides the first comprehensive analysis of urinary stone composition and associated risk factors in Qatar, offering valuable insights into urolithiasis patterns in a diverse population. Future prospective studies with larger and more balanced ethnic representation are needed to refine prevention strategies and optimize patient management.

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