A fresh look at oral chemolysis for non symptomatic kidney stones. Potassium citrate and Allopurinol combination. A Prospective Comparative Analysis

A fresh look at oral chemolysis for non symptomatic kidney stones. Potassium citrate and Allopurinol combination. 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Potassium citrate and Allopurinol combination. A Prospective Comparative Analysis Alper Coşkun, Utku CAN, Cengiz ÇANAKÇI, Bilal ERYILDIRIM This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3804014/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract PURPOSE: To compare the results of oral chemolysis of nonopaque and semi-opaque kidney stones using potassium citrate (PS) and allopurinol + potassium citrate (ALPS) prospectively without advanced metabolic analysis. MATERIAL and METHODS: Between 2020 and 2022, 47 patients aged 19-60 years with non-obstructive, semi-opaque, and nonopaque kidney stones of 8-13 mm in size detected by non-contrast tomography were prospectively investigated, and oral chemolysis (potassium citrate 10 mEq 2x2, allopurinol 10 mEq 2x2) was initiated. Patients were divided into two groups: potassium citrate (PS) and allopurinol + potassium citrate (ALPS), according to the treatment to be received. The essential characteristics of the groups, monthly laboratory values throughout the process, and the stone size measured by non-contrast tomography at the initial presentation and the control visit were recorded and compared. RESULTS: The most common stone localization was in the inferior calyx. There were no statistically significant differences between the groups regarding age, gender, size, location, or stone side The mean stone size was 11.01±2.27 mm in the PS group and 11.1±2.03 mm in the ALPSS group before treatment. After treatment, a significant change was observed in these values in both groups; however, there was no statistical difference between the groups. (p: <0.001), (p: 0.115) There was a meaningful range in the mean urine pH of all patients after treatment. (p: <0.001), Urea (BUN), creatinine, and glomerular filtration rate (GFR) values did not change significantly in either group. CONCLUSION: Potassium citrate-based urinary alkalisation can be started for nonopaque and semi-opaque kidney stones without metabolic analysis if the urine pH is appropriate. Allopurinol, in combination with potassium citrate, has no therapeutic advantage. Allopurinol lowe calyx oral chemolysis potassium citrate stone analysis Figures Figure 1 Introduction The primary treatment modalities for kidney stones are extracorporeal shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PCNL). [ 1 , 2 ] Despite the fact that these procedures have been in use for a long time, developing a non-invasive treatment modality has always been a priority. Both ureteral stenting and chemolysis via percutaneous nephrostomy were attempted many years ago, but because minimally invasive methods are always on the agenda, these methods are no longer used. [ 3 ] Urinary alkalisation is now the most commonly choiced non-invasive treatment for urinary tract stone disease. Potassium citrate (PS), sodium bicarbonate, and magnesium bicarbonate have been the most popular molecules in this treatment.[ 3 ] In today's urological practice, the most commonly used oral chemolysis molecule in cases of urinary calculi with hypocitraturia, hypercalciuria, hyperoxaluria, and hyperuricosuria is PS. It has been suggested that this molecule can be used without urometabolic analyses due to its wide range of indications.[ 4 , 5 ] Aside from the molecules used in oral chemolysis, allopurinol, a xanthine oxidase inhibitor, has long been used in the treatment of uric acid stones. Allopurinol has been shown to protect against uric acid stones and to reduce the size of the stones.[ 6 , 7 ] The status of follow-up and invasive treatment for non-symptomatic kidney stones less than 1 cm in diameter is still debatable, and metabolic analysis is not always possible. Considering this situation, we started potassium citrate and allopurinol + potassium citrate treatment in some of the patients with urinary pH below seven who were admitted to our outpatient clinic and who were found to have kidney stones with an average size of 10 mm as a result of imaging, and we tried to obtain prospective data by comparing the results of these treatments prospectively. Material and Methods Between March 2020 and February 2022, 76 patients aged 19–60 years who were admitted to the urology outpatient clinic of Kartal Dr. Lutfi Kirdar City Hospital between March 2020 and February 2022 and who were diagnosed with nonobstructive, semi and nonopaque 8–13 mm kidney stones below with a mean Hounsfeld Units (HU) 600 by non-contrast tomography were included in the study. Eight of these patients were excluded due to treatment refusal due to recurrent pain, five due to comorbidities, four due to low glomerular filtration rate (GFR), and two due to solitary kidney. In the remaining 57, the informed consent form was completed. Patients were divided into two groups as: potassium citrate (PS) and allopurinol + potassium citrate (ALPS). PS was started at a dose of 10 mEq 2x2 and allopurinol 300 mg 1x1. Age, gender, stone size (mm), location and side (right/left), HU, stone skin distance, body mass index (BMI), duration of treatment, urine pH, urea and creatinine values before and after treatment, and whether there is spontaneous passage during treatment were recorded. Six patients from the PS group and four from the PSAL group were excluded from the study due to insufficient follow-up. Thus, 47 patients were included in the study.(Fig. 1 ) Patients were invited to monthly controls throughout their treatment, and satisfaction with treatment, symptomatic status, and spontaneous passage were questioned. Participants in the PSAL group were also informed that they should be fed a purine-poor diet. In addition, every month, complete urinalysis, urea, and creatinine levels were measured. Treatment was typically continued for 6–7 months. Non-contrast tomography was used to determine the size of the stone after treatment. Statistical Analysis; all qualitative and quantitative data were transferred to SPSS 22.0 (IBM® SPSS® Statistics V22.0, 2013, USA). Statistical results were obtained by comparing the groups within and between each other. Independent Samples t-test, Paired sample t-test, and Pearson Chi-Square test were used for statistical analysis, and p < 0.05 was considered statistically significant. Results Nineteen of the 47 patients were female, with 21 in the potassium citrate (PS) group and 26 in the potassium citrate + allopurinol (PSAL) group. The average age was 45 years, and 24 stones were in the right kidney. There were no patients with bilateral kidney stones. When the patients were classified according to the calyceal localization of the stone, the most common case was in the lower calyx with 29 patients. Of all stones, 63% were nonopaque, and 17% were semi-opaque. There was no statistically significant difference between the groups in terms of age, stone size, Hounsfield unit (HU) values, and stone opacity. (Table 1 ) Table 1 Characteristics of the groups and their comparison with each other Potassium citrate (PS) (n:21) Allopurinol + Potassium citrate (ALPS) (n:26) p Age (years) median (IQR) 45,5 ± 10,7 41 ± 10,1 49 ± 10,1 0,936** Gender 0,266* Female n:19 6 12 Male n: 28 14 14 BMI (kg/m2), median (IQR) 30,07 ± 3,9 28,1 ± 2,15 31,6 ± 4,21 0,009** Stone location (kidney) 0,894* Upper calyx n:0 Middle calyx n:4 1 3 Renal pelvis n:13 5 8 Lower calyx n:29 13 14 Side of the stone 0,456* Right n:24 12 16 Left n:22 8 10 Hounsfield units (HU), median (IQR) 667,3 ± 194,4 634,8 ± 162,7 692,4 ± 215,5 0,111** Opacity status 0,509* Non-opaque 29(63,1) 12 17 Semi opaque 17(36,9) 8 9 Stone skin distance (mm) 10,22 ± 1,89 9,67 ± 1,9 10,65 ± 1,79 0,551** Duration of treatment (month) 6,54 ± 2,23 5,75 ± 1,86 7,15 ± 2,34 0,192** * Chi-Square, ** Independent Samples t Test, BUN: Blood Urea Nitrogen, IQR: Interquartile range In the post-treatment controls of the patients, a significant change was observed in the stone size, and the mean urine pH was measured monthly.(p < 0.001) However, no patient was found to have a urine pH above 7. Before treatment, the mean urea (BUN) value was 25.5, while the mean urea value measured monthly was 27.6.(p:0.026) No significant difference was observed in creatinine and glomerular filtration rate (GFR) values before and after treatment. (Table 2 ) Table 2 Comparison of all patients before and after oral chemolysis All Patients (n)Mean ± SD. Potassium citrate (PS) (n:21) Allopurinol + Potassium citrate (ALPS) (n:26) p** Stone size before treatment (mm) 11,08 ± 2,11 11,01 ± 2,27 11,1 ± 2,03 0,816** Stone size after treatment (mm) 8,43 ± 3,42 9,34 ± 2,27 7,73 ± 3,99 0,115** p* < 0,001* < 0,001* < 0,001* Urea (BUN) Before Treatment 25,51 ± 6,26 24,68 ± 5,51 26,15 ± 6,81 0,435** Urea(BUN) After Treatment 27,6 ± 5,96 26,44 ± 4,0 28,5 ± 7,05 0,235** p* 0,026* 0,259* 0,049* Pre-Treatment Creatinine 0,76 ± 0,15 0,74 ± 0,13 0,78 0,351** After Treatment Creatinine 0,82 ± 0,18 0,80 ± 0,17 0,83 0,654** p* 0,014* 0,058* 0,123* Pre-Treatment GFR 100,65 ± 15,05 103,39 ± 15,26 98,54 0,283** Post-Treatment GFR 96,2 ± 19,84 99,1 ± 20,72 94,06 0,398** p* 0,001* 0,040* 0,01* Pre-Treatment urine ph 5,89 ± 0,37 5,97 ± 0,37 5,83 ± 0,36 0,224 Post-Treatment urine ph 6,34 ± 0,31 6,42 ± 0,37 6,27 ± 0,24 0,114 p* < 0,001 < 0,001 < 0,001 * Paired sample t test, ** Independent Samples t Test, BUN: Blood urea nitrogen GFR: Glomeruler filtration rate Both groups showed a significant decrease in stone size after treatment; however, there was no significant difference in the change in stone size when the groups were compared with each other (p:0.115) (Table 2 ). Discussion Urolithiasis is one of the most often diagnosed conditions in urology with a worldwide prevalence ranging from 5 to 10%. The main determinants in the surgical and medical treatment of kidney stones are the size, location, obstruction status, and type of stone.[ 1 ] Surgical modalities are independent of the biochemical structure of the stone; however, the success of treatment in chemolysis was directly related to urine pH and stone analysis. Urinary alkalisation is the purpose goal of treatment and has been used for a long time. The best-known chemolysis has been described for uric acid stones. [ 8 – 11 ] The American Urological Association and European Association of Urology guidelines recommend offering potassium citrate (PC) therapy to patients with recurrent calcium stones and low (or relatively low) urinary citrate levels.[ 1 , 12 ] With this knowledge, it has been proposed that HU parameters will also be useful in predicting stone composition when selecting patients for oral chemolysis [ 16 ] Chemolysis without stone analysis has always been contentious, as have the stones that should be included in this group. In a recent study by Tsaturyan et al., potassium citrate, sodium bicarbonate, and magnesium bicarbonate were started in patients thought to have uric acid stones and significant results were obtained. [ 17 ] Diri et al. also reported that urine pH measurement and X-ray features could provide information about the metabolic type of the stone and that for possible uric acid stones, oral hemolysin can be started. [ 18 ] It has long been debated whether allopurinol, a xanthine oxidase inhibitor used in the medical treatment of uric acid stones, has an effect on calcium-dominant kidney stones. [ 6 , 19 , 20 ] Generally, it has been supported that it prevents calcium oxalate stone formation secondary to hyperuricosuria.[ 21 , 22 ] With this assumption, we aimed to predict whether the combined use of PS/PSAL makes a difference in treatment by including non/semi-opaque kidney stone patients in our study. We should note that our results provide a preliminary conclusion that the addition of allopurinol is not significantly superior to standard treatment. The significant reduction in stone size in both treatments is attributed primarily to urinary alkalization caused by the use of potassium citrate. Another fundamental test in the metabolic investigation of kidney stones is the 24-hour urine specimen. In general, 24-hour urine supersaturation levels are suggested as the standard for forecasting the likelihood of stone development, particularly of calcium-dominant stones. [ 1 , 12 ] However, in a recent survey, it was reported that large centers dealing with stones routinely perform 24-hour urine analysis, but they do not agree that this analysis is the best method and there is uncertainty about how urine analysis should be performed and how the data should be interpreted. In addition, it has recently come to the fore that urine analysis at certain times of the day may be more informative than 24-hour urine analysis. [ 23 , 24 ] We agree that the lack of 24-hour urine analysis is one of the most open-to-interpretation points of our study. However, we believe that checking the urine pH in our patients' monthly comprehensive urinalysis before and during treatment is sufficient. We should also add that there are issues with patient compliance when it comes to collecting 24-hour urine samples. The small number of patients is another limitation of our study. We attribute this to the fact that the number of patients presenting with non or semi-opaque kidney stones was generally insufficient, and our patients preferred a more definitive treatment. Another criticism could be directed towards the fact that the average length of treatment was six months. Our opinion on this subject is that more significant stone-free rates can be obtained with more prolonged treatment. Conclusion For nonopaque or semi-opaque nonobstructive kidney stones, oral chemolysis based on urine alkalization is a safe and efficient treatment that, in the right individuals, can be administered without the need for stone analysis. The use of allopurinol in combination with potassium citrate is not significantly superior. Even without 24-hour urine analysis, urine analysis at regular intervals may be sufficient. Again, different results can be obtained with prospective and multicentric long-term studies involving more patients. Declarations Acknowledgment: For his critical review and valuable contributions, thank you to Prof. Dr. Kemal SARICA. Conflict of Interest: No conflict of interest was declared by the authors . Financial Disclosure: The authors declared that this study has received no financial support . Author Contributions Conceptualization : Prof. Dr.Bilal ERYILDIRIM Methodology: Dr.Alper COŞKUN, Dr.Utku CAN Formal analysis and investigation: Dr.Alper COŞKUN Writing - original draft preparation: Dr.Alper COŞKUN, Dr.Cengiz ÇANAKÇI Resources: Dr.Alper COŞKUN, Dr.Utku CAN, Dr.Cengiz ÇANAKÇI Supervision: Dr.Alper COŞKUN, Prof. Dr.Bilal ERYILDIRIM Acknowledgment: For his critical review and valuable contributions, thank you to Prof. Dr. Kemal SARICA. Conflict of Interest: No conflict of interest was declared by the authors . Financial Disclosure: The authors declared that this study has received no financial support . Ethics committee approval: 30.06.2022 IRB number: 2022/514/228/38 References Türk C, Petřík A, Sarica K, Seitz C, Skolarikos A, Straub M et al (2016) EAU Guidelines on Diagnosis and Conservative Management of Urolithiasis. Eur Urol 69(3):468–474. 10.1016/j.eururo.2015.07.040 Geraghty RM, Davis NF, Tzelves L, Lombardo R, Yuan C, Thomas K et al (2023) Best Practice in Interventional Management of Urolithiasis: An Update from the European Association of Urology Guidelines Panel for Urolithiasis 2022. Eur Urol Focus 9(1):199–208. 10.1016/j.euf.2022.06.014 Bernardo NO, Smith AD (2000) Chemolysis of urinarycalculi. 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Urolithiasis 48(6):501–507. 10.1007/s00240-020-01204-8 Diri A, Diri B (2018) Management of staghorn renal stones. Ren Fail 40(1):357–362. 10.1080/0886022X.2018.1459306 Fellström B, Backman U, Danielson BG, Holmgren K, Johansson G, Lindsjö M et al (1985) Allopurinol treatment of renal calcium stone disease. Br J Urol 57(4):375–379. 10.1111/j.1464-410x.1985.tb06291.x Coe FL, Raisen L (1973) Allopurinol treatment of uric-acid disorders in calcium-stone formers. Lancet 20(1):129–131. 10.1016/s0140-6736(73)90197-9 Xu H, Zisman AL, Coe FL, Worcester EM (2013) Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother 14(4):435–447. 10.1517/14656566.2013.775250 Moe OW, Xu LHR (2018) Hyperuricosuric calcium urolithiasis. J Nephrol 31(2):189–196. 10.1007/s40620-018-0469-3 Ferraro PM, Arrabal-Polo MÁ, Capasso G, Croppi E, Cupisti A, Ernandez T et al (2019) A preliminary survey of practice pattern sacrossseveral European kidney stone centers and a call for action in developing shared practice. Urolithiasis 47(3):219–224. 10.1007/s00240-019-01119-z Williams JC Jr, Gambaro G, Rodgers A, Asplin J, Bonny O, Costa-Bauzá A et al (2021) Urine and stone analysis for the investigation of the renal stone former: a consensus conference. Urolithiasis. ; 49 (1): 1–16. 10.1007/s00240-020-01217-3 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3804014","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":263449817,"identity":"827ea069-bee8-4631-8ef4-c197e37f1e0b","order_by":0,"name":"Alper Coşkun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDCCA0D8AIjZ5A+DmBIyxGlJAGJ+CTYQJcFDvBbJGTwGID5hLXy3DzB+SNxhk29wu+fzqxs1FjwM7IePbsCnRfJcArNE4pk0yw13zm6zzjkGdBhPWtoNfFoMzgDdn9h22MDgQO424xw2oBYJHjNCWph/JLb9B2rJeWac8484LWxAWw4YSM7IYX6c20aEFskzjG0WiWeSDfh5jpkx5/ZJ8LAR8gvfGebDNz7usDNgY29+/DnnW50cP/vhY3i1MDAwNoAQCLBJgEn8yhG6QID5A1GqR8EoGAWjYMQBAPozSWAxmXCqAAAAAElFTkSuQmCC","orcid":"","institution":"Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi","correspondingAuthor":true,"prefix":"","firstName":"Alper","middleName":"","lastName":"Coşkun","suffix":""},{"id":263449819,"identity":"add159a8-503e-43a3-baef-b8dca1fc8154","order_by":1,"name":"Utku CAN","email":"","orcid":"","institution":"Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Utku","middleName":"","lastName":"CAN","suffix":""},{"id":263449820,"identity":"b00d5082-78ff-44de-bf15-c53fb904603a","order_by":2,"name":"Cengiz ÇANAKÇI","email":"","orcid":"","institution":"Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Cengiz","middleName":"","lastName":"ÇANAKÇI","suffix":""},{"id":263449823,"identity":"a2fc8da2-721b-4b59-9900-3b89ba997222","order_by":3,"name":"Bilal ERYILDIRIM","email":"","orcid":"","institution":"Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Bilal","middleName":"","lastName":"ERYILDIRIM","suffix":""}],"badges":[],"createdAt":"2023-12-25 10:14:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3804014/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3804014/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49077903,"identity":"a5d5318a-1509-40bd-945b-9cba4fbfd029","added_by":"auto","created_at":"2024-01-02 19:12:12","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":220065,"visible":true,"origin":"","legend":"\u003cp\u003eGroups and exclusion criteria\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3804014/v1/273321c8c177a35cd5924c70.jpeg"},{"id":50741591,"identity":"31f312c8-d8af-4738-8d95-8733a0f8b1d8","added_by":"auto","created_at":"2024-02-06 16:00:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":402111,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3804014/v1/3625cfbd-507f-4199-9d6e-16e28b58e550.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A fresh look at oral chemolysis for non symptomatic kidney stones. Potassium citrate and Allopurinol combination. A Prospective Comparative Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe primary treatment modalities for kidney stones are extracorporeal shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PCNL). [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Despite the fact that these procedures have been in use for a long time, developing a non-invasive treatment modality has always been a priority. Both ureteral stenting and chemolysis via percutaneous nephrostomy were attempted many years ago, but because minimally invasive methods are always on the agenda, these methods are no longer used. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eUrinary alkalisation is now the most commonly choiced non-invasive treatment for urinary tract stone disease. Potassium citrate (PS), sodium bicarbonate, and magnesium bicarbonate have been the most popular molecules in this treatment.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In today's urological practice, the most commonly used oral chemolysis molecule in cases of urinary calculi with hypocitraturia, hypercalciuria, hyperoxaluria, and hyperuricosuria is PS. It has been suggested that this molecule can be used without urometabolic analyses due to its wide range of indications.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Aside from the molecules used in oral chemolysis, allopurinol, a xanthine oxidase inhibitor, has long been used in the treatment of uric acid stones. Allopurinol has been shown to protect against uric acid stones and to reduce the size of the stones.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe status of follow-up and invasive treatment for non-symptomatic kidney stones less than 1 cm in diameter is still debatable, and metabolic analysis is not always possible. Considering this situation, we started potassium citrate and allopurinol\u0026thinsp;+\u0026thinsp;potassium citrate treatment in some of the patients with urinary pH below seven who were admitted to our outpatient clinic and who were found to have kidney stones with an average size of 10 mm as a result of imaging, and we tried to obtain prospective data by comparing the results of these treatments prospectively.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eBetween March 2020 and February 2022, 76 patients aged 19\u0026ndash;60 years who were admitted to the urology outpatient clinic of Kartal Dr. Lutfi Kirdar City Hospital between March 2020 and February 2022 and who were diagnosed with nonobstructive, semi and nonopaque 8\u0026ndash;13 mm kidney stones below with a mean Hounsfeld Units (HU) 600 by non-contrast tomography were included in the study. Eight of these patients were excluded due to treatment refusal due to recurrent pain, five due to comorbidities, four due to low glomerular filtration rate (GFR), and two due to solitary kidney. In the remaining 57, the informed consent form was completed. Patients were divided into two groups as: potassium citrate (PS) and allopurinol\u0026thinsp;+\u0026thinsp;potassium citrate (ALPS). PS was started at a dose of 10 mEq 2x2 and allopurinol 300 mg 1x1. Age, gender, stone size (mm), location and side (right/left), HU, stone skin distance, body mass index (BMI), duration of treatment, urine pH, urea and creatinine values before and after treatment, and whether there is spontaneous passage during treatment were recorded. Six patients from the PS group and four from the PSAL group were excluded from the study due to insufficient follow-up. Thus, 47 patients were included in the study.(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients were invited to monthly controls throughout their treatment, and satisfaction with treatment, symptomatic status, and spontaneous passage were questioned. Participants in the PSAL group were also informed that they should be fed a purine-poor diet. In addition, every month, complete urinalysis, urea, and creatinine levels were measured. Treatment was typically continued for 6\u0026ndash;7 months. Non-contrast tomography was used to determine the size of the stone after treatment.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical Analysis;\u003c/b\u003e all qualitative and quantitative data were transferred to SPSS 22.0 (IBM\u0026reg; SPSS\u0026reg; Statistics V22.0, 2013, USA). Statistical results were obtained by comparing the groups within and between each other. Independent Samples t-test, Paired sample t-test, and Pearson Chi-Square test were used for statistical analysis, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eNineteen of the 47 patients were female, with 21 in the potassium citrate (PS) group and 26 in the potassium citrate\u0026thinsp;+\u0026thinsp;allopurinol (PSAL) group. The average age was 45 years, and 24 stones were in the right kidney. There were no patients with bilateral kidney stones. When the patients were classified according to the calyceal localization of the stone, the most common case was in the lower calyx with 29 patients. Of all stones, 63% were nonopaque, and 17% were semi-opaque. There was no statistically significant difference between the groups in terms of age, stone size, Hounsfield unit (HU) values, and stone opacity. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the groups and their comparison with each other\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePotassium citrate (PS) (n:21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAllopurinol\u0026thinsp;+\u0026thinsp;Potassium citrate (ALPS) (n:26)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years) median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45,5\u0026thinsp;\u0026plusmn;\u0026thinsp;10,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;10,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;10,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,936**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0,266*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e n:19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e n: 28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30,07\u0026thinsp;\u0026plusmn;\u0026thinsp;3,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28,1\u0026thinsp;\u0026plusmn;\u0026thinsp;2,15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31,6\u0026thinsp;\u0026plusmn;\u0026thinsp;4,21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,009**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eStone location (kidney)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0,894*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUpper calyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMiddle calyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRenal pelvis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLower calyx\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSide of the stone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0,456*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRight\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLeft\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHounsfield units (HU), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e667,3\u0026thinsp;\u0026plusmn;\u0026thinsp;194,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e634,8\u0026thinsp;\u0026plusmn;\u0026thinsp;162,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e692,4\u0026thinsp;\u0026plusmn;\u0026thinsp;215,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,111**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOpacity status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0,509*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNon-opaque\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(63,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSemi opaque\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(36,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStone skin distance (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10,22\u0026thinsp;\u0026plusmn;\u0026thinsp;1,89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9,67\u0026thinsp;\u0026plusmn;\u0026thinsp;1,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,65\u0026thinsp;\u0026plusmn;\u0026thinsp;1,79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,551**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of treatment (month)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,54\u0026thinsp;\u0026plusmn;\u0026thinsp;2,23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,75\u0026thinsp;\u0026plusmn;\u0026thinsp;1,86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,15\u0026thinsp;\u0026plusmn;\u0026thinsp;2,34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,192**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Chi-Square, ** Independent Samples t Test, BUN: Blood Urea Nitrogen,\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIQR: Interquartile range\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the post-treatment controls of the patients, a significant change was observed in the stone size, and the mean urine pH was measured monthly.(p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) However, no patient was found to have a urine pH above 7. Before treatment, the mean urea (BUN) value was 25.5, while the mean urea value measured monthly was 27.6.(p:0.026) No significant difference was observed in creatinine and glomerular filtration rate (GFR) values before and after treatment. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of all patients before and after oral chemolysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll Patients (n)Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePotassium citrate (PS) (n:21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAllopurinol\u0026thinsp;+\u0026thinsp;Potassium citrate (ALPS) (n:26)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep**\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStone size before treatment (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11,08\u0026thinsp;\u0026plusmn;\u0026thinsp;2,11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11,01\u0026thinsp;\u0026plusmn;\u0026thinsp;2,27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11,1\u0026thinsp;\u0026plusmn;\u0026thinsp;2,03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,816**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStone size after treatment (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8,43\u0026thinsp;\u0026plusmn;\u0026thinsp;3,42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9,34\u0026thinsp;\u0026plusmn;\u0026thinsp;2,27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,73\u0026thinsp;\u0026plusmn;\u0026thinsp;3,99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,115**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrea (BUN) Before Treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25,51\u0026thinsp;\u0026plusmn;\u0026thinsp;6,26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24,68\u0026thinsp;\u0026plusmn;\u0026thinsp;5,51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,15\u0026thinsp;\u0026plusmn;\u0026thinsp;6,81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,435**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUrea(BUN) After Treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27,6\u0026thinsp;\u0026plusmn;\u0026thinsp;5,96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26,44\u0026thinsp;\u0026plusmn;\u0026thinsp;4,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28,5\u0026thinsp;\u0026plusmn;\u0026thinsp;7,05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,235**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,026*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,259*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,049*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-Treatment Creatinine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,76\u0026thinsp;\u0026plusmn;\u0026thinsp;0,15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,74\u0026thinsp;\u0026plusmn;\u0026thinsp;0,13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,351**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAfter Treatment Creatinine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,82\u0026thinsp;\u0026plusmn;\u0026thinsp;0,18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,80\u0026thinsp;\u0026plusmn;\u0026thinsp;0,17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,654**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,014*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,058*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,123*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-Treatment GFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100,65\u0026thinsp;\u0026plusmn;\u0026thinsp;15,05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103,39\u0026thinsp;\u0026plusmn;\u0026thinsp;15,26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98,54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,283**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost-Treatment GFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96,2\u0026thinsp;\u0026plusmn;\u0026thinsp;19,84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99,1\u0026thinsp;\u0026plusmn;\u0026thinsp;20,72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94,06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,398**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,040*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,01*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-Treatment urine ph\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,89\u0026thinsp;\u0026plusmn;\u0026thinsp;0,37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,97\u0026thinsp;\u0026plusmn;\u0026thinsp;0,37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,83\u0026thinsp;\u0026plusmn;\u0026thinsp;0,36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost-Treatment urine ph\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,34\u0026thinsp;\u0026plusmn;\u0026thinsp;0,31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6,42\u0026thinsp;\u0026plusmn;\u0026thinsp;0,37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,27\u0026thinsp;\u0026plusmn;\u0026thinsp;0,24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,114\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Paired sample t test, ** Independent Samples t Test, BUN: Blood urea nitrogen\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGFR: Glomeruler filtration rate\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBoth groups showed a significant decrease in stone size after treatment; however, there was no significant difference in the change in stone size when the groups were compared with each other (p:0.115) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eUrolithiasis is one of the most often diagnosed conditions in urology with a worldwide prevalence ranging from 5 to 10%. The main determinants in the surgical and medical treatment of kidney stones are the size, location, obstruction status, and type of stone.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Surgical modalities are independent of the biochemical structure of the stone; however, the success of treatment in chemolysis was directly related to urine pH and stone analysis. Urinary alkalisation is the purpose goal of treatment and has been used for a long time. The best-known chemolysis has been described for uric acid stones. [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The American Urological Association and European Association of Urology guidelines recommend offering potassium citrate (PC) therapy to patients with recurrent calcium stones and low (or relatively low) urinary citrate levels.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] With this knowledge, it has been proposed that HU parameters will also be useful in predicting stone composition when selecting patients for oral chemolysis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eChemolysis without stone analysis has always been contentious, as have the stones that should be included in this group. In a recent study by Tsaturyan et al., potassium citrate, sodium bicarbonate, and magnesium bicarbonate were started in patients thought to have uric acid stones and significant results were obtained. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Diri et al. also reported that urine pH measurement and X-ray features could provide information about the metabolic type of the stone and that for possible uric acid stones, oral hemolysin can be started. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIt has long been debated whether allopurinol, a xanthine oxidase inhibitor used in the medical treatment of uric acid stones, has an effect on calcium-dominant kidney stones. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Generally, it has been supported that it prevents calcium oxalate stone formation secondary to hyperuricosuria.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] With this assumption, we aimed to predict whether the combined use of PS/PSAL makes a difference in treatment by including non/semi-opaque kidney stone patients in our study.\u003c/p\u003e \u003cp\u003eWe should note that our results provide a preliminary conclusion that the addition of allopurinol is not significantly superior to standard treatment. The significant reduction in stone size in both treatments is attributed primarily to urinary alkalization caused by the use of potassium citrate.\u003c/p\u003e \u003cp\u003eAnother fundamental test in the metabolic investigation of kidney stones is the 24-hour urine specimen. In general, 24-hour urine supersaturation levels are suggested as the standard for forecasting the likelihood of stone development, particularly of calcium-dominant stones. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] However, in a recent survey, it was reported that large centers dealing with stones routinely perform 24-hour urine analysis, but they do not agree that this analysis is the best method and there is uncertainty about how urine analysis should be performed and how the data should be interpreted. In addition, it has recently come to the fore that urine analysis at certain times of the day may be more informative than 24-hour urine analysis. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] We agree that the lack of 24-hour urine analysis is one of the most open-to-interpretation points of our study. However, we believe that checking the urine pH in our patients' monthly comprehensive urinalysis before and during treatment is sufficient. We should also add that there are issues with patient compliance when it comes to collecting 24-hour urine samples.\u003c/p\u003e \u003cp\u003eThe small number of patients is another limitation of our study. We attribute this to the fact that the number of patients presenting with non or semi-opaque kidney stones was generally insufficient, and our patients preferred a more definitive treatment. Another criticism could be directed towards the fact that the average length of treatment was six months. Our opinion on this subject is that more significant stone-free rates can be obtained with more prolonged treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFor nonopaque or semi-opaque nonobstructive kidney stones, oral chemolysis based on urine alkalization is a safe and efficient treatment that, in the right individuals, can be administered without the need for stone analysis. The use of allopurinol in combination with potassium citrate is not significantly superior. Even without 24-hour urine analysis, urine analysis at regular intervals may be sufficient. Again, different results can be obtained with prospective and multicentric long-term studies involving more patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003eFor his critical review and valuable contributions, thank you to Prof. Dr. Kemal SARICA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e No conflict of interest was declared by the authors\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u003c/strong\u003e The authors declared that this study has received no financial support\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization\u003c/strong\u003e: Prof. Dr.Bilal ERYILDIRIM\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u0026nbsp;\u003c/strong\u003eDr.Alper COŞKUN, Dr.Utku CAN\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFormal analysis and investigation:\u0026nbsp;\u003c/strong\u003eDr.Alper COŞKUN\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting - original draft preparation:\u0026nbsp;\u003c/strong\u003eDr.Alper COŞKUN, Dr.Cengiz \u0026Ccedil;ANAK\u0026Ccedil;I\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResources:\u003c/strong\u003e Dr.Alper COŞKUN, Dr.Utku CAN, Dr.Cengiz \u0026Ccedil;ANAK\u0026Ccedil;I\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupervision:\u003c/strong\u003e Dr.Alper COŞKUN, Prof. Dr.Bilal ERYILDIRIM\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003eFor his critical review and valuable contributions, thank you to Prof. Dr. Kemal SARICA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e No conflict of interest was declared by the authors\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u003c/strong\u003e The authors declared that this study has received no financial support\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics committee approval:\u003c/strong\u003e 30.06.2022 IRB number: 2022/514/228/38\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eT\u0026uuml;rk C, Petř\u0026iacute;k A, Sarica K, Seitz C, Skolarikos A, Straub M et al (2016) EAU Guidelines on Diagnosis and Conservative Management of Urolithiasis. 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Urolithiasis. ; 49 (1): 1\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00240-020-01217-3\u003c/span\u003e\u003cspan address=\"10.1007/s00240-020-01217-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Allopurinol, lowe calyx, oral chemolysis, potassium citrate, stone analysis","lastPublishedDoi":"10.21203/rs.3.rs-3804014/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3804014/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePURPOSE: To compare the results of oral chemolysis of nonopaque and semi-opaque kidney stones using potassium citrate (PS) and allopurinol + potassium citrate (ALPS) prospectively without advanced metabolic analysis. MATERIAL and\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMETHODS: Between 2020 and 2022, 47 patients aged 19-60 years with non-obstructive, semi-opaque, and nonopaque kidney stones of 8-13 mm in size detected by non-contrast tomography were prospectively investigated, and oral chemolysis (potassium citrate 10 mEq 2x2, allopurinol 10 mEq 2x2) was initiated. Patients were divided into two groups: potassium citrate (PS) and allopurinol + potassium citrate (ALPS), according to the treatment to be received. The essential characteristics of the groups, monthly laboratory values throughout the process, and the stone size measured by non-contrast tomography at the initial presentation and the control visit were recorded and compared.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRESULTS: The most common stone localization was in the inferior calyx. There were no statistically significant differences between the groups regarding age, gender, size, location, or stone side The mean stone size was 11.01±2.27 mm in the PS group and 11.1±2.03 mm in the ALPSS group before treatment. After treatment, a significant change was observed in these values in both groups; however, there was no statistical difference between the groups. (p: \u0026lt;0.001), (p: 0.115) There was a meaningful range in the mean urine pH of all patients after treatment. (p: \u0026lt;0.001), Urea (BUN), creatinine, and glomerular filtration rate (GFR) values did not change significantly in either group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCONCLUSION: Potassium citrate-based urinary alkalisation can be started for nonopaque and semi-opaque kidney stones without metabolic analysis if the urine pH is appropriate. Allopurinol, in combination with potassium citrate, has no therapeutic advantage.\u003c/p\u003e","manuscriptTitle":"A fresh look at oral chemolysis for non symptomatic kidney stones. Potassium citrate and Allopurinol combination. A Prospective Comparative Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 19:12:07","doi":"10.21203/rs.3.rs-3804014/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a2376b74-e62c-4fcd-9ec9-322cefb7beff","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-06T15:52:34+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-02 19:12:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3804014","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3804014","identity":"rs-3804014","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}