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Review

Unveiling the Burden of Nephrolithiasis in Low- and Lower-Middle Income Countries: A Review on Its Presentation, Risk Factors, Treatment Practices, and Future Directions

by
Murtadha Almusafer
1,2,
Hussein Issa
3,
Margarita Eleni Paraskevopoulou
4,
Evangelos N Symeonidis
5,
Kamran Hassan Bhatti
2,6,
Mohamad Moussa
3,
Athanasios Papatsoris
2,7 and
Georgios Tsampoukas
2,8,*
1
Department of Surgery, College of Medicine, University of Basrah, Basrah 61004, Iraq
2
U-Merge Ltd. (Urology for Emerging Countries), London 14561, UK
3
Department of Urology, Al Zahraa Hospital, University Medical Center, Lebanese University, Beirut 2067 7201, Lebanon
4
Medical School, Queen Mary University of London, London E1 2AD, UK
5
Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
6
Urology Department, Hamad Medical Corporation, Doha 3050, Qatar
7
Department of Urology, University Hospital of Athens, 151 26 Athens, Greece
8
Department of Urology, Homerton Healthcare NHS Foundation Trust, London E9 6SR, UK
*
Author to whom correspondence should be addressed.
Soc. Int. Urol. J. 2024, 5(5), 361-370; https://doi.org/10.3390/siuj5050055
Submission received: 2 June 2024 / Revised: 26 September 2024 / Accepted: 30 September 2024 / Published: 18 October 2024

Abstract

:
Background: Nephrolithiasis, or kidney stone disease, presents a significant global health burden, with global incidence rates and treatment practices varying widely. This study aims to discuss the epidemiology, risk factors, treatment modalities, and challenges for nephrolithiasis in the lower half of the World Bank rankings; that is, in low- and lower-middle-income countries. Methods: A comprehensive literature review was conducted using PubMed for each country on the list, focusing on studies published from January 2000 onwards and reporting data on prevalence, risk factors, treatment practices, and economic implications. Results: Nephrolithiasis represents a significant burden for healthcare systems, with noteworthy geographical variability in prevalence possibly dependent on socioeconomic status and gender. Risk factors include dietary habits, climate, pollution, and infectious diseases. Treatment practices in some regions still rely on open surgery due to limited access to advanced endourological techniques, while other regions demonstrate high proactivity in research. The burden is exacerbated by inadequate healthcare infrastructure and training. Conclusions: Addressing nephrolithiasis in challenging economic circumstances requires targeted interventions, including improved access to modern treatment methods, enhanced training for healthcare professionals, and better socioeconomic and environmental conditions. Future research should focus on region-specific strategies and the development of sustainable healthcare solutions.

1. Introduction

Nephrolithiasis, or kidney stone disease, demonstrates significant geographical diversity and varying rates in its occurrence across different continents. Since 1990, global incidence trends have been mixed, with Eastern Europe, Central Europe, and Southeast Asia experiencing declines, while the Caribbean and Central Asia have seen increases [1]. Despite the declining rates in some regions, the number of new cases, recurrence rates, and the number of emergency and outpatient visits highlight its impact on healthcare. In economies like the U.S., the management of nephrolithiasis incurs substantial costs, estimated to be USD billions [2]. Moreover, factors such as low income, education level, insurance coverage, mental health, and gender disparities further restrict access to optimal care [3]. Current social and economic settings may exacerbate disparities, as access to modern technology, research capabilities, and training varies globally. A survey of over 100 urologists from 27 low- and middle-income countries revealed that only 19% believe that there are sufficient professionals to meet patient needs and to provide standard care in their countries [4]. Additionally, a recent Cochrane review identified gaps in health equity in nephrolithiasis research, particularly the under-representation of low-income countries in systematic reviews; thus, examining socioeconomic status alongside traditional factors is necessary to fully understand the burden of kidney stone disease [5]. In Sub-Saharan Africa, despite a shift toward minimally invasive procedures like external shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and ureteroscopy (URS), many regions still depend on open surgery [6]. This situation underscores the need for investment in medical infrastructure and training. Last, but not least, some regions have geographic burdens, as changes in climate, rainfall, and temperature correlate with lithogenesis [7]. The need for development in urological care within emerging economies is supported by organisations like U-Merge, which promotes knowledge transfer and research (U-merge—Home). In this paper, we aim to discuss the challenges of urolithiasis in the lower half of the World Bank rankings, namely the low- and lower-middle-income countries, discussing its presentation and the practices and particular risk factors associated with nephrolithiasis, and we comment on areas where further action and initiatives appear necessary.

2. Material and Methods

According to the World Bank database for 2024, the income status of countries is determined using their Gross National Income (GNI) per capita. Countries with a GNI of USD 1135 or less are classified as low-income countries. Countries with a GNI between USD 1136 and USD 4465 are classified as lower-middle-income countries. Countries with a GNI ranging between USD 4465 and USD 13.845 are categorised as upper-middle-income countries and those exceeding the latter are considered high-income economies (World Bank Country and Lending Groups—World Bank Data Help Desk). Taking into consideration that over 3 billion of people live in lower-middle-income countries, the exploration of healthcare burden in these regions is topical (Population, total—Lower middle income | Data (worldbank.org)). In our research, both lower-middle-income countries (LMICs) and low-income countries (LICs) were included to capture a broader range of economic and healthcare conditions, which reflects the diversity within the lower half of the World Bank rankings. The countries are presented in Table 1.
Then, a literature review was conducted using the PubMed database. The following search string was used in the PubMed Advanced Search Builder: (nephrolithiasis OR “Kidney stones” OR urolithiasis OR “Renal stones” [Title/Abstract]) AND (country). Studies published from January 2000 to the present were evaluated in order to focus on recent trends and data. Articles that report on the prevalence, risk factors, economic burden, research landscape or management strategies of nephrolithiasis which pose challenges were evaluated. Conference abstracts, editorials, opinion pieces, and non-peer-reviewed literature were excluded but searched for crossover references.

3. Prevalence and Presentation

Understanding the prevalence and presentation of urolithiasis across various continents and subcontinents reveals critical insights into the regional differences and commonalities in this significant health issue.

3.1. Asia

In Iran, the estimated national lifetime prevalence of urolithiasis is 6.6%; the prevalence is higher in men than in women (7.9% vs. 5.3%), urban men had no increased risk compared with rural men, and the Baluch ethnicity showed the highest prevalence at 18%. The authors advised that socioeconomic factors, including dietary habits, healthcare access, and environmental exposures, may have influenced these variations [8]. The same authors reported a prevalence rate of recurrent urolithiasis at 2.6%, whereas residence in urban areas increased the risk, indicating that effects of urbanisation on diet, occupation, and income may complicate kidney stone disease and recurrence [9]. A survey from India, using the Ballabgarh health information system, showed a lifetime prevalence of 7.9%, with a mean diagnosis age of 37.6 years, indicating a high prevalence in the working-age group [10]. In Manipur, an equal gender distribution was observed, but aging was associated with more stones, and 68.4% of the patients were overweight. Stones were more common among students, housewives, office workers, and business people, and less common among retirees and farmers, indicating a modern lifestyle’s adverse effects [11]. In Pakistan, kidney stone prevalence ranges from 1% to 5%, with a recent study finding that 2.8% of individuals undergoing routine CT scans had asymptomatic stones [12,13]. In Northern Vietnam, 231 patients with urinary stones showed a male predominance, with a male-to-female ratio of 1.96:1. Seasonal trends indicated fewer stones during the Lunar New Year (February) and Ghost Month (August) [14].

3.2. Africa

A study in Kenya on 67 patients, with a median age of 42, with urolithiasis over 17 months showed that 46% of the stones were in the ureter and that there was a male majority of 79.1% [15]. In regional Nigeria, upper tract calculi were the third most commonly urological diagnosis, affecting 10.3% of new patients, though this was lower compared with the northern region [16]. A study from Cameroon found that nephrolithiasis caused obstructive uropathy in 35% of cases, with stents used urgently in 19% of patients [17]. Examining paediatric renal diseases in resource-poor settings, a study in Sudan analysed a population of 150 hospitalised children, the majority of whom (83%) were from low socioeconomic backgrounds. Urolithiasis was found in 15.5% of cases, whereas the site of renal calculi in these patients included one or both kidneys and/or ureters in 67.7% of cases and the bladder in 32.3% [18]. Another interesting aspect is presented by a study in Western Algeria. During 2012–2019, authors analysed data from 1104 stone formers, reporting a male dominance, overweight in 57% of cases, 53.1% having a poor education level, and males also experiencing more recurrences than female [19]. A study in Tunisia (2003–2010) of 310 children (ages 3 months to 19 years) found a male predominance, with 70.7% of stones in the upper urinary tract. Calcium oxalate stones were the most common (52.6%) and increased with age, while struvite stones were more frequent in boys aged 2–9 years [20].

4. Risk Factors

The role of the environment was highlighted in several studies. A study in Vietnam analysed 58,330 hospital admissions from 2003 to 2015 and found that each 1 °C increase in daily mean temperature over a week significantly raised the odds of hospitalisation for kidney diseases, including urolithiasis (OR: 1.09) [21]. In Sri Lanka’s Central Highlands, a study linked high kidney stone incidence to drinking water geochemistry, finding significant differences in pH, hardness, and mineral levels between patient and non-patient areas, with water composition being influenced by rock–water interactions and mineral weathering being a key factor in stone formation, highlighting the environmental impact on health [22]. During Operation Serval in Mali, 11.7% of repatriated French soldiers had renal colic, with 29% having a history of kidney stones. Dehydration and high temperatures were key contributors, suggesting the need for targeted preventive measures and further research [23].
A possible link between stones and metabolic factors was reported in a few regions. In Jordan, among 8346 patients, 68.1% were categorised as obese or overweight, suggesting that higher body weight may contribute to urinary stone development, emphasising the need for weight management in prevention [24]. A study in Ghana found that crystalluria was common in type 2 diabetes mellitus patients, with a prevalence of 17.5% compared with 5.0% in non-diabetics, mostly consisting of calcium oxalate (12.7%), with higher fasting blood glucose levels and lower urine pH being significant factors [25]. A study in Pakistan found that key risk factors for nephrolithiasis included an age of 15–30, male gender, illiteracy, low socioeconomic status, inadequate water intake, use of tap water, high vegetable consumption, sedentary lifestyle, family history of renal stones, and high BMI, indicating that socioeconomic factors and lifestyle choices significantly impact its prevalence [26]. A study of 9932 participants from Iran identified key risk factors for kidney stones as male gender, hypertension, obesity, diabetes, alcohol consumption, opium use, hookah smoking, higher socioeconomic status, and lower purified water consumption, highlighting the multifactorial nature of kidney stone formation and the need for comprehensive prevention strategies [27]. In Lebanon, where calcium oxalate stones are most common, risk factors include male gender, smoking, hypertension, and diabetes, with incidence peaking in July [28].
Dietary factors and water consumption have also been linked to kidney stone formation. A study in Iran found that the daily consumption of tea, soft drinks, coffee, bread, meat, liver, fish, and canned foods significantly increased kidney stone risk, highlighting the crucial role of dietary modifications [29]. In southwest Iran, a study of over 10,000 participants found an 18.7% prevalence of stones, with higher intake of carbohydrates and copper as associated factors, suggesting the need for further evaluation [30]. In India, a study of 1266 kidney stone formers found that over 50% drank less than 3 litres of water daily, but the acidity, hardness, solutes, electrical conductivity, and salinity of the water did not differ compared to areas with zero prevalence, implying that other elements of the water may be responsible for stone formation [31]. Finally, chewing betel quid in the Indian subcontinent, which encompasses 20–40% of the population, has been linked to hypercalciuria, alkaline urine, and low urinary citrate, all of which increase calcium oxalate stone formation [32].
In Tajikistan, a study of 1180 patients aged 14–76 found higher urolithiasis rates in areas with poor environmental conditions, high pollution, natural mineralisation, water hardness, and elevated chloride and sulphate levels, highlighting the crucial impact of water quality and pollution on health [33]. Groundwater contamination with cadmium in India may disturb calcium metabolism, linking it to urolithiasis [34]. A 2011 study in Telangana State, India, found increased fluoride in drinking water, making it unsuitable and increasing the risk of toxicities, including stone formation [35].
In Burkina Faso, a retrospective study linked schistosomiasis with urolithiasis, highlighting infectious agents as critical risk factors in endemic areas [36]. In Mali, a study of 23 patients with urinary bilharziasis-related stones found pain and fever in over 50% of cases, with 91.3% requiring surgical treatment [37]. The pathophysiology of stone formation in schistosomiasis follows a distinct pathway of chronic inflammation leading to tissue damage and calcifications that serve as nuclei for urinary stone formation; therefore, a history of infection should be considered a possible risk factor for urolithiasis in endemic areas.
Last, but not least, a study in Somalia on 204 patients with renal stones found a significant correlation between dental calculi grade and renal stone size, suggesting a link between dental health and kidney stones due to socioeconomic status [38].

5. Stone Composition

A multicentric study from U-merge reported that in Egypt, India, and Pakistan, calcium-containing stones were most common, but uric acid stones were surprisingly high at 30%, 34%, and 25%, respectively, and were higher than in upper- and high-income countries (except Bulgaria and Poland), which could potentially be linked to diet, water quality, or environmental influences regulated by income [39]. In neighbouring Nepal, calcium stones were most common (>70%) followed by uric acid, struvite, and cystine stones [40,41]. In Algeria, stone composition appears similar to industrialised countries, with calcium oxalate being the most common (up to 75%) followed by calcium phosphate and uric acid stones [19]. Similar stone composition was reported also in Morocco, where a population of 123 samples showed calcium oxalate as the most common at 61%, followed by uric acid stones at 15% [42]. In a study from Congo, although calcium oxalate stones remained the most common, the prevalence of anhydrous uric acid stones (22.7%) was higher than that typically observed in high-income countries [43]. Furthermore, a study of 100 kidney stones in Burkina Faso showed that while 65% of the stones primarily contained calcium oxalate, a notable 18% had opaline silica as the second main component. This pattern suggests a unique factor influencing stone formation that is potentially linked to the regular consumption of clay (geophagy), a behaviour believed to contribute to this anomaly [44]. Nevertheless, in the area of Maiduguri in Nigeria, calcium-containing stones account for the vast majority of cases, followed by uric acid stones [45].

6. Treatment and Research Landscape

Focusing on surgical norms, a recent study from Ethiopia observed that while 51.5% of patients were treated initially with endoscopic procedures, 43.6% still underwent open stone surgery, whereas endoscopy was significantly associated with incomplete stone clearance, particularly in patients with multiple stones [46]. In a survey study published in 2024 involving 46 centres across 27 African countries, only 34 centres have access to endourological equipment, but only 30 perform endourology, and these began practising endourology less than 10 years ago. Notably, open surgery is still employed to treat kidney stones in 20 centres [47]. Governance challenges have also been highlighted. In Yemen, a study of the retention of encrusted ureteral stents was enlightening; the study found poor patient compliance (47.5%), an inability to return to the hospital due to financial reasons (30%), delayed referral after ESWL to the endourology department for timely stent replacement or removal (12.5%), and poor communication between patients and physicians (10%) [48]. Despite the increasing popularity of endoscopic techniques, surgeons in some regions remain mindful of cost constraints. In Ghana, semi-rigid ureteroscopy (URS) was the most common modality (53%), followed by PCNL (37.4%), and flexible URS (5%); however, the flexible ureteroscope was reserved for exceptional cases—for example, if the rigid scope was unable to reach stones in the pelvis and calyces—a pragmatic approach balancing surgical options with economic realities [49]. Finally, a study from Cameroon reveals that metabolic screening for nephrolithiasis is rarely conducted, and blood tests for calcium, phosphorus, and uric acid were performed in only 15.8%, 0.8%, and 12.5% of cases, respectively. The authors advised that financial constraints may deprive patients of necessary medical tests [50].
In the research landscape, our review indicates that the majority of countries in the low-income group have not demonstrated high levels of evidence-based research in the field of urology. This lack of research achievements can be attributed to several factors, including limited resources, insufficient funding, and inadequate infrastructure for conducting high-quality studies. Additionally, challenges such as political instability, lack of access to advanced medical technologies, and brain drain, where skilled professionals migrate to higher-income countries, further hinder research progress in these regions. On the other hand, countries such as Egypt, India, Pakistan, and Jordan have made remarkable efforts in urological research, particularly in endourology and percutaneous stone surgery [51,52,53,54,55,56]. These nations have conducted high-quality studies focusing on post-operative pain management and the handling of complex stone cases, including randomised studies, which have been pivotal in enhancing the evidence base and advancing training in PCNL and URS.

7. Comment

Nephrolithiasis appears to represent a substantial burden for all low- and lower-middle-income countries. Environmental factors like climate, water quality, pollution, and dehydration significantly contribute to this burden due to the geographical terrain and socioeconomic conditions prevalent in most of these countries. Addressing these issues through improving water infrastructure, controlling pollution, and promoting hydration and heat mitigation may help to reduce the incidence and impact of kidney stone disease in these regions. As secondary prevention, utilising properly selected metaphylaxis in resource-strained healthcare systems, may provide a cost-effective solution particularly for urate or infectious stones, by urine pH modification and phytotherapy [57,58,59]. Moreover, economic restraints possibly impact the management of nephrolithiasis by limiting access to necessary treatment services. Solutions such as increasing healthcare funding, subsidising treatment costs, and seeking international aid may improve healthcare accessibility and reduce the burden of kidney stone disease in these areas. It is notable that although some LMICs, like Egypt, Pakistan, and India, appear to perform well and lead in managing nephrolithiasis, not all countries in this group enjoy such advancements. Enhancing training programs and fellowships, fostering regular international collaboration, and further developing local training facilities may help empower urolithiasis care in areas needing development. Countries like Egypt, Pakistan, and India could take a leading role in setting examples and providing support. Potential areas for development and suggestions are presented in Table 2.
Our paper has several limitations. It is not a systematic review, and the data collected are heterogeneous, so the reader must be cautious in drawing definitive conclusions. Additionally, the classification of countries by income does not fully explain the differences observed in healthcare practices and outcomes, necessitating a critical interpretation of our findings. Furthermore, some regions are under-represented due to a lack of available research or data, leading to potential gaps in our analysis. Last but not least, the suggestions provided are based on general insights and not on a detailed review of specific measures to address these challenges. While associations between certain factors and nephrolithiasis have been discussed, these do not imply causation, and further research is needed to establish definitive causal links. Despite these limitations, our findings underscore the need for more comprehensive and systematic research to better understand and address nephrolithiasis in the lower half of the World Bank rankings.

8. Conclusions

Nephrolithiasis represents a significant health burden in low- and lower-middle-income countries, driven by environmental, economic, and healthcare infrastructure challenges. Factors such as climate, water quality, pollution, and dehydration play crucial roles, compounded by limited access to advanced medical technologies and training. Addressing these issues requires enhancing healthcare funding, improving infrastructure, promoting public health education, and fostering international collaborations. Despite the limitations of our paper, including heterogeneous data and non-systematic review methods, our findings highlight the urgent need for targeted interventions and further research to better manage and reduce the incidence of kidney stone disease in these vulnerable regions.

Author Contributions

Conceptualization, M.A. and G.T.; methodology, G.T.; validation, M.A. and A.P. and G.T.; formal analysis, M.A., H.I., M.E.P., E.N.S., K.H.B., M.M., A.P. and G.T.; investigation, M.A., H.I., M.E.P., E.N.S., K.H.B., M.M., A.P. and G.T.; resources, M.A., H.I., M.E.P., E.N.S., K.H.B., M.M., A.P. and G.T.; data curation, G.T.; writing—original draft preparation, M.A., H.I., M.E.P., E.N.S., K.H.B., M.M., A.P. and G.T.; writing—review and editing, M.A., H.I., M.E.P., E.N.S., K.H.B., M.M., A.P. and G.T.; visualization, G.T.; supervision, A.P. and G.T.; project administration, G.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

Dr Almusafer, Dr Bhatti, Dr Papatsoris and Dr Tsampoukas are member of U-merge. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Table 1. Low- and lower-middle-income countries.
Table 1. Low- and lower-middle-income countries.
ContinentIncome CategoryCountries
AfricaLow Burkina Faso, Burundi, Central African Republic, Chad, Congo (Dem. Rep.), Eritrea, Ethiopia, Gambia, Guinea-Bissau, Liberia, Madagascar, Malawi, Mali, Mozambique, Niger, Rwanda, Sierra Leone, Somalia, South Sudan, Sudan, Togo, Uganda
Lower-middle Algeria, Angola, Benin, Cabo Verde, Cameroon, Comoros, Congo (Rep.), Côte d’Ivoire, Djibouti, Eswatini, Ghana, Guinea, Kenya, Lesotho, Mauritania, Morocco, Nigeria, São Tomé and Principe, Senegal, Tanzania, Tunisia, Zambia, Zimbabwe
AsiaLow Afghanistan, Korea (Dem. People’s Rep.), Syrian Arab Republic, Yemen (Rep.)
Lower-middle Bangladesh, Bhutan, Cambodia, Egypt, India, Iran, Jordan, Kyrgyz Republic, Lao PDR, Lebanon, Micronesia, Mongolia, Myanmar, Nepal, Pakistan, Philippines, Sri Lanka, Syria, Tajikistan, Timor-Leste, Uzbekistan, Vietnam
AmericaLow Haiti
Lower-middle Bolivia, El Salvador, Guatemala, Honduras, Nicaragua
EuropeLow -
Lower-middle Ukraine
OceaniaLow -
Lower-middle Kiribati, Papua New Guinea, Samoa, Solomon Islands, Vanuatu
Table 2. Challenges in LIC and LMICs and possible areas of action.
Table 2. Challenges in LIC and LMICs and possible areas of action.
Challenges
Environmental Health campaigns (hydration, diet, special factors) and screening
Screening programs during peak seasons to manage kidney stones
Strict regulations to reduce pollution/management of industrial waste
Warning systems for heatwaves and guidelines for prevention
Economic restraints Increase funding for auditing and research
Invest in early detection and standardisation of diagnostic methods
Collaborations between governments and non-governmental organisations (NGOs) among clinicians worldwide
International aid and support
Training needsDeveloping international training and fellowship opportunities
Fostering partnerships and collaboration between urological societies
Invest in local facilities with up-to-date technology
GovernanceFormulate national health policies and guidelines
School health programs
Public awareness campaigns and community workshops
Healthcare provider training in guidelines, auditing, and research
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Almusafer, M.; Issa, H.; Paraskevopoulou, M.E.; Symeonidis, E.N.; Bhatti, K.H.; Moussa, M.; Papatsoris, A.; Tsampoukas, G. Unveiling the Burden of Nephrolithiasis in Low- and Lower-Middle Income Countries: A Review on Its Presentation, Risk Factors, Treatment Practices, and Future Directions. Soc. Int. Urol. J. 2024, 5, 361-370. https://doi.org/10.3390/siuj5050055

AMA Style

Almusafer M, Issa H, Paraskevopoulou ME, Symeonidis EN, Bhatti KH, Moussa M, Papatsoris A, Tsampoukas G. Unveiling the Burden of Nephrolithiasis in Low- and Lower-Middle Income Countries: A Review on Its Presentation, Risk Factors, Treatment Practices, and Future Directions. Société Internationale d’Urologie Journal. 2024; 5(5):361-370. https://doi.org/10.3390/siuj5050055

Chicago/Turabian Style

Almusafer, Murtadha, Hussein Issa, Margarita Eleni Paraskevopoulou, Evangelos N Symeonidis, Kamran Hassan Bhatti, Mohamad Moussa, Athanasios Papatsoris, and Georgios Tsampoukas. 2024. "Unveiling the Burden of Nephrolithiasis in Low- and Lower-Middle Income Countries: A Review on Its Presentation, Risk Factors, Treatment Practices, and Future Directions" Société Internationale d’Urologie Journal 5, no. 5: 361-370. https://doi.org/10.3390/siuj5050055

APA Style

Almusafer, M., Issa, H., Paraskevopoulou, M. E., Symeonidis, E. N., Bhatti, K. H., Moussa, M., Papatsoris, A., & Tsampoukas, G. (2024). Unveiling the Burden of Nephrolithiasis in Low- and Lower-Middle Income Countries: A Review on Its Presentation, Risk Factors, Treatment Practices, and Future Directions. Société Internationale d’Urologie Journal, 5(5), 361-370. https://doi.org/10.3390/siuj5050055

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