Stesura Seveso Archivio Italiano di Urologia e Andrologia 2023; 95(3):11361 1 ORIGINAL PAPER INTRODUCTION Worldwide, nephrolithiasis is one of the commonest uro- logic diseases. In the last decades, the prevalence of nephrolithiasis has changed, with prevalence ranges from 7% to 13%, 5% to 9%, and 1% to 5% in North America, Europe, and Asia, respectively (1). The wide prevalence ranges among countries reflect several multifactorial condi- tions including age, sex, race, climate, occupation, dietary habits, fluid intake, genetic and metabolic diseases (2). In Asia, the prevalence and incidence of urolithiasis have increased in most of the countries specifically more in the south Asian countries than in the north Asian countries (5.5% to 11.6% compared to 2.6% to 7.2%, respectively) (3). This is because of the higher temperature and exces- sive sunshine exposure in the south countries than that in the north countries. Saudi Arabia is located in the west Asian region and due to its high temperature and semi- arid climate the prevalence of urinary tract stones was documented to be rising. During the period from 1989 through 2008, the prevalence rate of urolithiasis has been increased from 6.8% (4) to 19.1% (5). Renal stone recurrence is a devastating health problem, which affects the patients’ health-related quality of life (6), as well as represents an extra economic burden for its management (7). In a prospective study, Trinchieri et al. studied the stone recurrence rate and risk after a first stone episode and found that 27% of patients developed symptomatic stone recurrence at mean follow-up of 7.5 years. In addition, age at onset of the disease was signifi- cantly lower for patients with ≥ 2 recurrence than those who had only 1 or no recurrence (8). Among Asian coun- tries, the reported recurrence rate of urolithiasis in the first year was about 6% to 17%, and at 5 years reaching up to 53%, while the lifetime risk of urinary stones recur- rence is estimated to be 60% to 80% (9). In Saudi Arabia, Abdel-Halim et al. reported a recurrence rate of renal stone ranging from 38.6% to 53.2% (4). Studies evaluating the risk factors of renal stone recur- rence are not common. Our study aimed to explore the demographic characteristics of primary renal stones for- Objectives: We evaluated the baseline char- acteristics, and risk factors of renal stone recurrence among Saudi Arabian patients after successful pri- mary stone treatment. Materials and methods: In this cross-sectional comparative study, we reviewed the medical records of patients who present- ed consecutively with a first renal stone episode from 2015 to 2021 and were followed-up by mail questionnaire, telephone interviews, and/or outpatient clinic visit. We included patients who achieved stone-free status after primary treatment. Patients were divided into two groups: group I (patients with first episode renal stone) and group Ⅱ (patients who developed renal stone recurrence). The study outcomes were to compare the demo- graphics of both groups and to evaluate the risk factors of renal stone recurrence after successful primary treatment. We used Student’s t-test, Mann Whitney test or chi-square (𝝌2) to com- pare variables between groups. Cox regression analyses were used to examine the predictors. Results: We investigated 1260 participants (820 males and 440 females). Of this number, 877 (69.6%) didn’t develop renal stone recurrence and 383 (30.4%) had recurrence. Primary treatments were percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), extracorporeal shock wave lithotripsy (ESWL), surgery and medical treatment in 22.5%, 34.7%, 26.5%, 10.3%, and 6%, respectively. After primary treatment, 970 (77%) and 1011 (80.2%) of patients didn’t have either stone chemical analysis or metabolic work-up, respectively. Multivariate logistic regression analysis revealed that male gender (OR: 1.686; 95% CI, 1.216-2.337), hypertension (OR: 2.342; 95% CI, 1.439-3.812), primary hyperparathy- roidism (OR: 2.806; 95% CI, 1.510-5.215), low fluid intake (OR: 28.398; 95% CI, 18.158-44.403) and high daily protein intake (OR: 10.058; 95% CI, 6.400-15.807) were predictors of renal stone recurrence. Conclusions: Male gender, hypertension, primary hyperparathy- roidism, low fluid intake and high daily protein intake increase the risk of renal stone recurrence among Saudi Arabian patients. KEY WORDS: Renal stone; Risk factors; Recurrence; Saudi Arabia. Submitted 5 April 2023; Accepted 28 May 2023 Evaluation of risk factors for recurrent renal stone formation among Saudi Arabian patients: Comparison with first renal stone episode Mohammed Alshehri1, Hind Alsaeed2, Malath Alrowili 2, Faisal Alhoshan3, Ali Abdel Raheem4, 5, Ayman Hagras5, 6 1 Department of Urology, King Abdullah bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 2 Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; 3 Prince Sultan Military Hospital, Taif, Saudi Arabia; 4 Department of Urology, King Saud Medical City, Riyadh, Saudi Arabia; 5 Department of Urology, Tanta University Hospital, Tanta, Egypt; 6 Division of Urology, Surgery Department, Sharurah Armed Forces Hospital, Sharurah, Saudi Arabia. DOI: 10.4081/aiua.2023.11361 Summary Archivio Italiano di Urologia e Andrologia 2023; 95(3):11361 M. Alshehri, H. Alsaeed, M. Alrowili, F. Alhoshan, A. Abdel Raheem, A. Hagras 2 mer, as well as the risk factors of renal stone recurrence after successful primary treatment in Saudi Arabia. We believe that the results of this study may provide an insight into ways that can help us to prevent the recur- rence of renal stones. MATERIALS AND METHODS Study design and ethical statement A prospective cross-sectional comparative study was car- ried out at four Saudi Arabia's tertiary centers in Riyadh, Taif and Sharurah cities. The study was approved by the institutional review boards and ethical committee of Princess Nourah bint Abdulrahman University and was performed in accordance with the ethical standards and the Helsinki declaration (Institutional review board “IRB” registration number: H-01-R-059). All patients included in our study signed a written informed consent. We reviewed the medical records of patients who present- ed consecutively with a first renal stone episode from 2015 to 2021 at urology departments of the participating centers. From March 2020 through March 2021, patients were interviewed either during their follow-up visits in the clinic or by telephone interviews to fill out a question- naire. A total of 1260 patients completed the question- naires successfully. Patients were divided into two groups: group I (patients with first episode renal stone) and group II (patients who developed renal stone recurrence). Inclusion and exclusion criteria Patients aged ≥ 18 years old with history of successful pri- mary renal stone treatments (i.e., medical or surgical) were included in the current study. We excluded patients with remaining stones after the initial stone episode, patient who had urinary tract malformation, urinary tract obstructive disease, history of pyeloplasty or ureteric reimplantation surgery, renal failure, chronic gastric dis- eases, and incomplete questionnaire data. Patients' characteristics Demographic and baseline patients' characteristics were retrieved from our database including age, gender, body mass index (BMI), medical comorbidities such as diabetes mellitus (DM), hypertension (HTN), cardiac diseases…etc, city of residency, nationality, family history of urolithia- sis, and history of recurrent urinary tract infection (UTI). Moreover, data regarding renal stone were gathered such as primary or recurrent renal stone, time to first recur- rence, frequency of recurrence, previous treatment meth- ods (either surgical or medical), chemical analysis of the stone, and routine metabolic work-up after successful primary treatment. Follow-up All patients were followed-up after treatment at 6 weeks, 3 months then yearly until the last visit. Routine postop- erative imaging study included Kidney-Ureter-Bladder (KUB) X-ray, urinary ultrasound (UUS), or computed tomography (CT) scan that were performed according to the surgeon preference and/or stone radiopacity. Stone- free status was defined as non-obstructing residual stone fragments of ≤ 2 mm in size detected at 3 months post- operatively on postoperative imaging studies (10). Recurrent renal stone was defined as new stone formation and/or stone growth during routine follow-up that was diagnosed radiologically (11). Patients' lifestyle information regarding the level of phys- ical activity per week and dietary habits were obtained through asking the patients to complete a previously published (12, 13) non-validated self-administered questionnaire including selected items (1 question for physical activity and 5 questions for dietary habit). Questionnaires were disseminated among patients either in the clinic during follow up visits and/or through tele- phone calls. The commonest dietary habits that are asso- ciated with increased risk of stone formation and recur- rence include; low fluid intake (< 1 liter/day), high salt diet (> 10 g/day), high protein intake (> 100 g/day), low- calcium diet (≤ 400 mg/day), and high intake of oxalate containing foods (14). Outcome measurement The primary outcome was to compare groups in order to evaluate the predictors of renal stone recurrence after suc- cessful primary treatment. The secondary outcome was to assess demographic characteristics of stone formers in Saudi Arabia. Statistical analysis Continuous variables were illustrated as mean ± standard deviation (SD) or median and interquartile range (IQR), whereas categorical variables were illustrated as frequency and percentages (%). To compare variables of group I and group II, we used the Student’s t-test, Mann Whitney test or chi-square (𝝌2) test to examine the statistical signifi- cance of normally distributed data, nonparametric data, or categorical data, respectively. A univariable and multivari- able Cox regression analyses were used to examine the predictors of renal stone recurrence. All tests were two- sided and P value of less than 0.05 was considered statis- tically significant. All tests used the SPSS version 23 software (IBM SPSS Statistics, IBM Corp., Armonk, NY, USA). RESULTS A total of 1260 participants (820 males and 440 females) with history of successful renal stone primary treatment completed the questionnaire and were included in our study. Baseline patients’ clinical and demographic data are summarized in (Table I). Median patients’ age was 29 years (IQR: 23-41), and median BMI was 25.3 kg/m2 (IQR: 21.8-29). The incidence of HTN was 10.2% and PHPT was 5.8%. Most of patients 811 (64.4%) are living in the central region of the country. Previous primary treatments were PCNL, RIRS, ESWL, surgery and medical treatment in 283 patients (22.5%), 437 patients (34.7%), 334 patients (26.5%), 130 patients (10.3%), and 76 patients (6%), respectively. Among the participants, 383 patients (30.4%) had recurrent renal stone and 877 patients (69.6%) didn’t develop recurrence after primary stone treatment. The median follow-up period from the onset of primary stone treatment was 32 Archivio Italiano di Urologia e Andrologia 2023; 95(3):11361 3 Predictors of renal stone recurrence months (IQR: 24-41). The median time to first recurrence of renal stone was 29 months (IQR: 14-35). After suc- cessful primary treatment, 970 (77%) and 1011 (80.2%) of patients didn’t have either stone chemical analysis or metabolic work-up, respectively. The comparison of patients with primary and recurrent renal stones is showed in (Table 2). No significant differ- Table 1. Baseline characteristic of patients with renal stone in Saudi Arabia (n = 1260). Age (yr): mean ± SD 32.5 ± 12.4 median (IQR) 29 (23-41) BMI (kg/m2): mean ± SD 25.9 ± 6.1 median (IQR) 25.3 (21.8-29) BMI classification, n (%) Underweight (< 18.5) 82 (6.5%) Normal (18.5-24.9) 525 (41.7%) Overweight and obese (> 25) 653 (51.8%) Gender, n (%) Female 440 (34.9%) Male 820 (65.1%) Chronic diseases, n (%) HTN 129 (10.2%) DM 98 (7.8%) Asthma 106 (8.1%) Hypercholesterolemia 101 (8%) PHPT 73 (5.8%) Gout 27 (2.1%) Residency, n (%) Central region 811 (64.4%) Eastern region 225 (17.9%) Western region 125 (9.9%) Southern region 55 (4.4%) Northern region 44 (3.5%) Nationality, n (%) Saudi 1191 (94.5%) Other 69 (5.5%) Physical activity, n (%) Low (≤ 1 day/week) 504 (40%) Moderate (2-4 days/week) 548 (43.5%) High (≥ 5 days/week) 208 (16.5%) Recurrence of kidney stones, n (%) First time 877 (69.6%) Recurrent ≥ 2 times 383 (30.4%) Family history of renal stone, n (%) No 854 (67.8%) Yes 406 (32.2%) History of UTI, n (%) No 721 (57.2%) Yes 539 (42.8%) Dietary habits, n (%) High salt diet (> 2 gm/day) 256 (20.3%) Low fluid intake (< 1 L/day) 459 (36.4%) High protein intake (≥ 3 times/week) 763 (60.6%) Low calcium intake (≤ 400 mg/day) 205 (16.3%) High oxalate containing foods 158 (12.5%) Stone chemical analysis, n (%) Yes 290 (23%) No 251 (19.9%) Nobody asked 719 (57.1%) Stone type, n (%) Calcium oxalate 120 (9.5%) Calcium phosphate 44 (3.5%) Cystine 54 (4.3%) Struvite 72 (5.7%) Unknown 970 (77%) Metabolic workup, n (%) Yes 249 (19.8%) No 294 (23.3%) Nobody asked 717 (56.9%) Previous treatment, n (%) PCNL 283 (22.5%) RIRS 437 (34.7%) ESWL 334 (26.5%) Surgery 130 (10.3%) Controlled diet + medical ttt 76 (6%) UUS: ultrasound scan, CTU; computed tompgraphy; HTN: hypertension; DM: diabetes mellitus; BMI: body mass index; PHPT: primary hyperparathyroidism; UTI: urinary tract infection; PCNL: percutaneous nephrostomy; RIRS: retrograde intrarenal surgery; ESWL: extracorporeal shockwave lithotripsy. Table 2. Comparing characteristic of patients with first time and recurrent renal stones. Primary stone Recurrent stone P-value Variables (Group I, n = 877) (Group II, n = 383) Age (yr), mean ± SD 31.3 ± 12.1 35.1 ± 12.6 0.000 BMI (kg/m2), mean ± SD 25.9 ± 6.1 26.2 ± 6.3 0.421 BMI classification, n (%) Underweight 56 (6.4%) 26 (6.8%) 0.492 Normal 375 (42.8%) 150 (39.2%) Overweight and obese 446 (50.9%) 207 (54%) Gender, n (%) Female 340 (38.8%) 100 (26.1%) 0.000 Male 607 (61.2%) 283 (73.9%) Hypertension (HTN), n (%) 73 (8.3%) 56 (14.6%) 0.001 Diabetes (DM), n (%) 63 (7.2%) 35 (9.1%) 0.253 Asthma, n (%) 71 (8.1%) 35 (9.1%) 0.581 Hypercholesterolemia, n (%) 62 (7.1%) 39 (10.2%) 0.071 Hyperparathyroidism, n (%) 41 (4.7%) 32 (8.4%) 0.013 Gout, n (%) 15 (1.7%) 12 (3.1%) 0.137 Residency, n (%) Central region 580 (66.1%) 231 (60.3%) 0.133 Eastern region 156 (17.8%) 69 (18%) Western region 82 (9.4%) 43 (11.2%) Southern region 33 (3.8%) 22 (5.7%) Northern region 26 (3%) 18 (4.7%) Nationality, n (%) Saudi 835 (95.2%) 356 (93%) 0.105 Other 42 (4.8%) 27 (7%) Physical activity, n (%) Low 363 (41.4%) 141 (36.8%) 0.300 Moderate 371 (42.3%) 177 (46.2%) High 143 (16.3%) 65 (17%) History of UTI, n (%) No 479 (54.6%) 242 (63.2%) 0.005 Yes 398 (45.4%) 141 (36.8%) Family history, n (%) No 607 (69.2%) 247 (64.5%) 0.101 Yes 270 (30.8%) 136 (35.5%) Dietary habits, n (%) High salt diet (yes) 180 (20.5%) 76 (19.8%) 0.782 Low fluid intake (yes) 191 (21.8%) 268 (70%) 0.000 High protein intake (yes) 507 (57.8%) 256 (66.8%) 003 Low calcium intake (yes) 151 (17.2%) 54 (14.1%) 0.168 High oxalate intake (yes) 105 (12%) 53 (13.8%) 0.358 Stone type, n (%) Calcium oxalate 49 (5.6%) 71 (18.5%) 0.000 Calcium phosphate 20 (2.3%) 24 (6.3%) Cystine 24 (2.7%) 30 (7.8%) Struvite 36 (4.1%) 36 (9.4%) Unknown 748 (85.3%) 222 (58%) Previous treatment, n (%) PCNL 203 (23.1%) 80 (20.9%) 0.654 RIRS 307 (35%) 130 (33.9%) ESWL 232 (26.5%) 102 (26.6%) Surgery 84 (9.6%) 46 (12%) Controlled diet + medical ttt 51 (5.8%) 25 (6.5%) UUS: ultrasound scan, CTU; computed tompgraphy; HTN: hypertension; DM: diabetes mellitus; BMI: body mass index; PHPT: primary hyperparathyroidism; UTI: urinary tract infection; PCNL: percutaneous nephrostomy; RIRS: retrograde intrarenal surgery; ESWL: extracorporeal shockwave lithotripsy. Archivio Italiano di Urologia e Andrologia 2023; 95(3):11361 M. Alshehri, H. Alsaeed, M. Alrowili, F. Alhoshan, A. Abdel Raheem, A. Hagras 4 ence was found in most variables (p > 0.05). Mean patients’ age was 35.1 ± 12.6 yr. in group I compared to 31.3 ± 12.1 yr. in group II (p = 0.000). More male patients were present in group II compared to group I (73.9% vs. 61.2%, p = 0.000, respectively). The rates of HTN, PHPT, low fluid intake, and high daily protein diet were significantly higher in group II (14.6% vs. 8.3% in group I, p = 0.001), (8.4% vs. 4.7% in group I, p = 0.013), (70% vs. 21.8 % in group I, p = 0.000) and (66.8% vs. 57.8% in group I, p = 0.003), respectively. Univariate logistic regression analysis showed that age, male patients, HTN, PHPT, history of UTI, low fluid intake, and high daily protein intake were associated with increased risk of renal stones recurrence (p < 0.05). Multivariate logistic regression analysis revealed that male patients (OR: 1.686; 95% CI, 1.216-2.337), HTN (OR: 2.342; 95% CI, 1.439-3.812), PHPT (OR: 2.806; 95% CI, 1.510-5.215), low fluid intake (OR: 28.398; 95% CI, 18.158-44.403) and high daily protein intake (OR: 10.058; 95% CI, 6.400-15.807) were predictors of renal stone recurrence. DISCUSSION In this prospective study, the risk factors and baseline characteristics of renal stone formers, as well as the pre- dictors of recurrent renal stone formations were investi- gated in Saudi Arabian. A total of 1260 patients (820 males and 440 females) were included in the analysis. The rate of kidney stone recurrence after successful pri- mary stone treatment was 30.4% among the participants. The results demonstrated that male gender, HTN, PHPT, low oral fluid intake and high daily protein intake were potential risk factors for recurrent kidney stone forma- tion. We believe that the result of our study may provide better insight into the prevention of kidney stones recur- rence through proper control and management of its risk factors. Renal stone recurrence is a common disease. Patients with renal stones have an increase chance of forming another stone in the future. Stones can recur as long as 10 years after the first episode (8). In our cohort, the overall renal stone recurrence rate was 30.4%. Among them, 11.3% of patients had two-time recurrences, 9.8% had three-time recurrences, and 9.4% had four-time recur- rences. Our results are in accordance with previous study reporting the recurrence rate of nephrolithiasis recur- rence of 38.6% to 53.2% in Saudi Arabia (4). In the pres- ent study, the median time of renal stone recurrence was 29 months (IQR: 14-35). Generally, following the initial episode, nephrolithiasis carries a high recurrence rate of 3.4 per 100 person-years, 7.1 after the second episode, 12.1 after the third episode, and 17.6 after the fourth episode or higher (15). Moreover, the natural cumulative recurrence stone rate was estimated to be 6 to 17%, 35%, and 52% at one year, five years, and ten years, respec- tively (15). Our study showed that the recurrent kidney stone rate was found to be significantly higher in men (56.6%) than in women (44.4%). In addition, male gender was identi- fied as a predictor for nephrolithiasis recurrence. This may be attributed to the hormonal differences between men and women. In women, estrogen stimulates the secretion of citric acid in urine and regulates the synthe- sis of 1,25-dihydroxy-vitamin D which are considered protective factors against nephrolithiasis. On the other hand, men’s androgen induces the urinary accumulation of uric acid, calcium, and oxalate which increase the risk of kidney stone formation (16, 17). Of note, 10.2% of the cases in our study had HTN and the odds of recurrent renal stone in HTN cases was 2.34 compared with non-HTN cases. Sahng et al. found that the risk of renal stone formation was directly associated with the incidence of HTN (18). Interestingly, in a recent study 29.7% of patients with nephrolithiasis had HTN (19). In a recent systematic review and meta-analysis, HTN was found to be one of the risk factors for renal stone recurrence (20). It worth note that, the exact mech- anism of renal stone formation in patients with HTN remains unclear, and only few studies have examined it. Table 3. Univariate and multivariate analysis of predictors of recurrent renal stone ≥ 2 times in Saudi patients. Univariable analysis Multivariable analysis Variable OR (95% CI) P-value OR (95% CI) P-value Age 1.025 (1.015-1.035) 0.000 BMI 1.008 (0.989-1.028) 0.421 BMI classification: Underweight Ref Normal 0.862 (0.521-1.424) 0.561 Overweight and obese 1.000 (0.610-1.637) 0.999 Male patient 1.794 (1.401-2.298) 0.000 1.686 (1.216-2.337) 0.002 HTN 1.886 (1.301-2.734) 0.001 2.342 (1.439-3.812) 0.001 DM 1.299 (0.844-2.001) 0.234 Asthma 0.142 (0.747-1744) 0.540 Hypercholesterolemia 1.490 (0.979-2.268) 0.063 PHPT 1.859 (1.152-3.001) 0.011 2.806 (1.510-5.215) 0.001 Gout 1.859 (0.862-4.010) 0.114 Residency: Central region Ref Eastern region 1.111 (0.805-1.532) 0.523 Western region 1.738 (0.935-3.231) 0.081 Southern region 1.647 (0.956-2.932) 0.072 Northern region 1.317 (0.883-1.963) 0.177 Saudi patient 0.663 (0.403-1.092) 0.107 Physical activity: Low Ref Moderate 1.228 (0.943-1.600) 0.127 High 1.170 (0.823-1.664) 0.381 History of UTI 1.426 (1.114-1.825) 0.005 Renal stone Family history 1.238 (0.960-1.595) 0.099 Dietary habits: High salt diet 0.959 (0.710-1.294) 0.782 Low fluid intake 8.370 (6.383-10.976) 0.000 28.398 (18.158-44.403) 0.000 High protein intake 1.471 (1.144-1.892) 0.003 10.058 (6.400-15.807) 0.000 Low calcium intake 0.789 (0.563-1.105) 0.168 High oxalate intake 1.181 (0.828-1.683) 0.358 Previous treatment: PCNL Ref RIRS 1.075 (0.772-1.495) 0.670 ESWL 1.116 (0.788-1.580) 0.538 Surgery 1.390 (0.892-2.164) 0.145 Diet + medical ttt 1.244 (0.722-2.143) 0.432 UUS: ultrasound scan, CTU; computed tompgraphy; HTN: hypertension; DM: diabetes mellitus; BMI: body mass index; PHPT: primary hyperparathyroidism; UTI: urinary tract infection; PCNL: percutaneous nephrostomy; RIRS: retrograde intrarenal surgery; ESWL: extracorporeal shockwave lithotripsy. Archivio Italiano di Urologia e Andrologia 2023; 95(3):11361 5 Predictors of renal stone recurrence Frequent changes in the levels of blood pressure have a direct effect on the urinary microbiomes, which may stimulate nephrolithiasis (21). Dietary habits play an important role in the renal stone formation. Excessive meat consumption and low fluid intake were considered as main risk factors for nephrolithiasis. Our study showed that in patients with recurrent kidney stones high protein intake rate was sig- nificantly higher (66.8%) than in primary stone formers (57.8%), similarly low fluid intake was significantly high- er (70% vs. 21.8%). High protein intake leads to acidifi- cation of urine, which stimulate the formation of calcium oxalate stone (22). Xu et al. found that each 500 mL increase in water intake was significantly associated with a reduced risk of kidney stone formation (RR = 0.93; 95% CI: 0.87, 0.98; p < 0.01). Additionally, daily water intake > 2000 mL decreases the risk of first kidney stone forma- tion by at least 8% compared to 1500 mL (23). PHPT is one of the listed risk factors for renal stone for- mation. It has been estimated that 20% of patients with PHPT have nephrolithiasis, and approximately 5% of patients who presented with renal stones have PHPT (24). Our results are in agreement with the aforemen- tioned results. Notably, 73 patients (5.8%) have PHPT in our cohort analysis. Moreover, the rate of patients with recurrent renal stone and PHPT was significantly higher (8.4%) than those without PHPT (4.7%), in addition, the odds of recurrent renal stone in PHPT patients was 2.8 compared with non-PHTP patients. The current study has limitations and strengths. The strength points of our study are the following: a prospec- tive study, large sample size (n = 1260), and extensive data gathering for the factors of interest related to stone formation and recurrence (e.g., age, sex, BMI, medical comorbidities, dietary habits, area of residency etc.). However, our study does not devoid of limitations, and the results have to be interpreted with caution. For instance, the short median follow-up period (32 months) may be not enough to estimate the actual rate of renal stone recurrence. Non-recurrent stone formers in this study are “patients who formed a first stone” although they may develop stone recurrence after longer follow-up peri- od. Also, stone composition and metabolic work-up results are unknown in 77% and 80.2% of patients, respectively. Excluding those patients was not possible to complete the analysis. 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Correspondence Mohammed Alshehri, MD mohammedalshehri95@yahoo.com Department of Urology, King Abdullah bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia Hind Alsaeed, MD alsaeedhindx@gmail.com Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia Malath Alrowili, MD pc435000386@gmail.com Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia Faisal Alhoshan, MD fmialhoshan@gmail.com Prince Sultan Military Hospital, Taif, Saudi Arabia Ali Abdel Raheem, MD, PhD (Corresponding Author) aliraheem82@yahoo.com a-hassan@ksmc.med.sa Urology Consultant, Urology Department, King Saud Medical City, Riyadh, Saudi Arabia Lecturer of Urology, Urology Department, Tanta University Hospital, Tanta, Egypt Ayman Hagras, MD ahagras80@yahoo.com Department of Urology, Faculty of Medicine, Tanta University, Tanta, Egypt Division of Urology, Surgery Department, Sharurah Armed Forces Hospital, Sharurah, Saudi Arabia Conflict of interest: The authors declare no potential conflict of interest.