Urine Microscopy Revealing a Metabolic Disorder: a Case Report
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Abstract Background Primary hyperoxaluria type 3 is a rare autosomal recessive disorder caused by HOGA1 mutations, leading to recurrent calcium oxalate nephrolithiasis. Diagnosis is often delayed, and 24-hour urine oxalate measurements can be unreliable in patients with normal kidney function. Urine microscopy can detect high-density calcium oxalate monohydrate crystals, providing a rapid diagnostic clue. Case Presentation A 31-year-old woman with recurrent nephrolithiasis since age 9 had undergone prior percutaneous nephrolithotomy and ureteroscopy. Urine microscopy revealed abundant COM crystals (280/mm³), and stone analysis showed mixed calcium phosphate, oxalate dihydrate, and COM. Genetic testing confirmed homozygous HOGA1 mutation (c.700 + 5G > T). Conservative management with hydration, dietary calcium, and potassium citrate normalized citrate but not crystalluria. Adjunctive phytate therapy led to disappearance of calcium oxalate monohydrate crystals within weeks. Renal function and residual stones remained stable over 24 months. Conclusion Detection of > 200 calcium oxalate monohydratecrystals/mm³ is highly suggestive of PH3. Urine microscopy is rapid, inexpensive, and complements genetic testing. Conservative therapy remains central, and adjunctive measures like phytate may help reduce crystallization risk.
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Urine Microscopy Revealing a Metabolic Disorder: a Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Urine Microscopy Revealing a Metabolic Disorder: a Case Report Diana Santos, Miguel Brito Lança, David Navarro, Pedro Baltazar, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8468051/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Mar, 2026 Read the published version in BMC Nephrology → Version 1 posted 18 You are reading this latest preprint version Abstract Background Primary hyperoxaluria type 3 is a rare autosomal recessive disorder caused by HOGA1 mutations, leading to recurrent calcium oxalate nephrolithiasis. Diagnosis is often delayed, and 24-hour urine oxalate measurements can be unreliable in patients with normal kidney function. Urine microscopy can detect high-density calcium oxalate monohydrate crystals, providing a rapid diagnostic clue. Case Presentation A 31-year-old woman with recurrent nephrolithiasis since age 9 had undergone prior percutaneous nephrolithotomy and ureteroscopy. Urine microscopy revealed abundant COM crystals (280/mm³), and stone analysis showed mixed calcium phosphate, oxalate dihydrate, and COM. Genetic testing confirmed homozygous HOGA1 mutation (c.700 + 5G > T). Conservative management with hydration, dietary calcium, and potassium citrate normalized citrate but not crystalluria. Adjunctive phytate therapy led to disappearance of calcium oxalate monohydrate crystals within weeks. Renal function and residual stones remained stable over 24 months. Conclusion Detection of > 200 calcium oxalate monohydratecrystals/mm³ is highly suggestive of PH3. Urine microscopy is rapid, inexpensive, and complements genetic testing. Conservative therapy remains central, and adjunctive measures like phytate may help reduce crystallization risk. Primary hyperoxaluria Urine microscopy crystalluria Nephrolithiasis case report Figures Figure 1 Introduction Primary hyperoxaluria type 3 (PH3) is an autosomal recessive disorder caused by HOGA1 mutations, resulting in overproduction of oxalate and recurrent calcium oxalate nephrolithiasis. 1 Diagnosis is often delayed due to nonspecific clinical presentation. While 24-hour urine oxalate measurements are standard, they can be unreliable in patients with normal kidney function due to incomplete acidification, crystal precipitation, or dietary influences. 1 Urine microscopy can detect high-density calcium oxalate monohydrate (COM) crystals, providing a sensitive and immediate clue for rare metabolic stone disorders. 2 We report a case in which urine microscopy images led to the diagnosis of PH3, highlighting its educational value for nephrologists. Case Report A 31-year-old woman presented with intermittent flank discomfort and a history of recurrent nephrolithiasis since age 9. She had undergone left percutaneous nephrolithotomy at 18 and flexible ureteroscopy at 28. Serum creatinine was 0.8 mg/dL, and estimated glomerular filtration rate was > 90 mL/min/1.73 m². Urine microscopy of first-morning specimens revealed abundant large COM crystals: 280/mm³ (Fig. 1 ). Fourier Transform Infrared spectroscopy of stones showed calcium phosphate (40%), calcium oxalate dihydrate (30%), and COM (30%). Two consecutive 24-hour urine collections showed isolated hyperoxaluria (45 and 72 mg/24 h, normal T), consistent with PH3. Table 1 Results of 24-hour urine collections of the patient’s initial evaluation Date Volume mL/24h Protein mg/24h Urea mmol/24h Creatinine mg/24h Uric acid mmol/24h Calcium mmol/24h Magnesium mmol/24h Citrate mg/24h Sodium mmol/24h Oxalate mg/24h Oxalate mg/L Nov 2022 2700 108 347 1289 2.87 3.40 55.4 577 97 45 16 Dec 2022 1900 78 290 1294 3.18 4.75 90.4 601 133 72 37.7 Initial conservative management included increased hydration (> 2 L/day), dietary calcium (1 g/day), and potassium citrate supplementation, which normalized urinary citrate, but crystalluria persisted after 14 months. Adjunctive phytate therapy (Lit-Control® pH Balance, 255 mg every 12 h) was introduced. Within several weeks, urine microscopy showed progressive reduction and eventual disappearance of COM crystals (Table 2 ). During 24 months of follow-up, renal function remained stable, residual stones were unchanged, and no adverse effects were observed. Table 2 . Patient’s follow up and treatment 24h urine CItrate mg/24h 24h urine Oxalate mg/24 Potassium citrate Lit Control pH Balance Urine Sediment Crystalluria Month 0 577 45 + 2 + 6 546 46 ✓ + 8 1066 74 ✓ + 13 1063 69 ✓ + 20 586 50 ✓ ✓ + 25 968 69 ✓ ✓ - 26 ✓ ✓ - Discussion Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism, characterized by excessive endogenous oxalate production, recurrent nephrolithiasis, and progressive risk of renal impairment. 1 Three genetically distinct forms are recognized: PH1, PH2, and PH3. PH1 is the most common and carries the poorest prognosis, whereas PH2 and PH3 are less frequent and typically follow a milder course. PH3 results from biallelic mutations in HOGA1, which encodes 4-hydroxy-2-oxoglutarate aldolase, a mitochondrial enzyme expressed in the liver and kidney. 1 Loss-of-function mutations in HOGA1 lead to glyoxylate accumulation and subsequent oxalate overproduction. Our patient presented with childhood-onset, recurrent nephrolithiasis and was diagnosed with PH3 after genetic confirmation of the homozygous splice-site mutation c.700 + 5G > T, one of the most frequently reported HOGA1 variants in Europe. 1 Although stone analysis revealed a mixed calcium oxalate and calcium phosphate composition, such findings are nonspecific and cannot differentiate PH3 from idiopathic stone disease, as mixed stones are common in PH2 and may occur in other conditions, including medullary sponge kidney, infection, or hyperparathyroidism. 2 Urine microscopy played a critical role in diagnosis. Detection of > 200 calcium oxalate monohydrate (COM) crystals/mm³ is highly suggestive of primary hyperoxaluria and was particularly important when only one of two 24-hour urine oxalate measurements was elevated. 1 , 3 Urine sediment microscopy not only aids diagnosis but also provides real-time feedback on lithogenic activity, allowing clinicians to assess the impact of therapeutic interventions before new stones are detectable by imaging. Persistent crystalluria indicates ongoing stone formation, whereas its resolution signals successful suppression of lithogenesis, as observed in this patient. Calcium oxalate crystallization is the most frequent form of crystalluria in human urine due to the very low solubility of calcium oxalate. The type of crystal depends mainly on the urinary calcium-to-oxalate molar ratio. 4 In hyperoxaluric conditions with normal or low calcium, the monohydrate form predominates, serving as a specific marker of hyperoxaluria, while the dihydrate form is less diagnostic. Urine oxalate measurements are prone to pre-analytical variability, and plasma oxalate is informative only in kidney failure, rarely available, and not useful in this patient. 1 While genetic testing provides a definitive diagnosis, it is costly, time-consuming, and not universally accessible; by contrast, urine microscopy is rapid, cost-effective, and widely available. 3 Management emphasizes urine dilution, citrate supplementation, and dietary calcium to reduce lithogenic risk . 1,5,6 In this patient, adjunctive phytate therapy coincided with disappearance of COM crystals, suggesting a potential role for crystallization inhibitors, though evidence remains limited, and phytate should not be considered primary therapy. 5 – 7 Phytate (inositol hexakisphosphate, InsP6) is a naturally occurring polyphosphate abundant in whole grains, legumes, nuts, and seeds. 8 It inhibits nucleation, growth, and aggregation of calcium oxalate and phosphate crystals, a mechanism supported by experimental and clinical data. 9 , 10 In our patient, supplementation with Lit-Control® pH Balance resulted in resolution of crystalluria, stabilization of stone burden, and preserved renal function over two years, highlighting its translational potential as an adjunctive therapy in PH3, where disease-specific treatments such as RNA interference are not established. 1 Stone removal should follow standard guidelines. Percutaneous nephrolithotomy is preferred for larger or complex stones, while extracorporeal shock wave lithotripsy may be considered selectively for smaller stones. 5 Conclusion Urine microscopy provided the critical visual clue leading to the diagnosis of a rare metabolic disorder. High-density COM crystalluria complements urinary oxalate measurements and offers a rapid, inexpensive diagnostic approach, particularly in patients with normal kidney function. Conservative therapy with hydration, citrate, and dietary calcium remains the mainstay of management, and adjunctive measures such as phytate may further reduce lithogenic risk. This case highlights the importance of integrating urine microscopy into routine evaluation of patients with recurrent nephrolithiasis. Declarations Consent for publication Written informed consent for publication of this case report and accompanying images was obtained from the patient. The authors confirm responsibility for the integrity and accuracy of the data and for the decision to submit the manuscript for publication. Author Contribution ContributionsDS – literature search, clinical data acquisition, data analysis, and manuscript drafting, editing, and review.MBL– clinical data acquisition and manuscript preparation, editing, and review.DN – manuscript review.PB – manuscript review.CJ – manuscript review.LCP – manuscript review.NMF – concept, study design, definition of intellectual content, manuscript editing, and critical manuscript review.All authors read and approved the final manuscript. Data Availability All data generated or analyzed during this study are included in this published article. Additional data are available from the corresponding author on reasonable request. References Groothoff JW, Metry E, Deesker L, Garrelfs S, Acquaviva C, Almardini R, Beck BB, Boyer O, Cerkauskiene R, Ferraro PM, Groen LA, Gupta A, Knebelmann B, Mandrile G, Moochhala SS, Prytula A, Putnik J, Rumsby G, Soliman NA, Somani B, Bacchetta J. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023;19(3):194–211. 10.1038/s41581-022-00661-1 . Epub 2023 Jan 5. PMID: 36604599. Daudon M, Bouzidi H, Bazin D. Composition and morphology of phosphate stones and their relation with etiology. Urol Res. 2010;38(6):459–67. Daudon M, Crystalluria. A marker for diagnosis and prognosis of crystallogenic pathologies and nephrolithiasis. Rev Fr Lab. 2013;455:67–73. Daudon M, Letavernier E, Frochot V, Haymann JP, Bazin D, Jungers P. Respective influence of calcium and oxalate urine concentration on the formation of calcium oxalate monohydrate or dihydrate crystals. C R Chim. 2016;19(11–12):1504–13. Skolarikos A, Somani B, Neisius A, Jung H, Petřík A, Tailly T, Davis N, Tzelves L, Geraghty R, Lombardo R, Bezuidenhout C, Gambaro G. Metabolic Evaluation and Recurrence Prevention for Urinary Stone Patients: An EAU Guidelines Update. Eur Urol. 2024;86(4):343–63. Epub 2024 Jul 27. PMID: 39069389. Demoulin N, Aydin S, Gillion V, Morelle J, Jadoul M. Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review. Am J Kidney Dis. 2022;79(5):717–27. 10.1053/j.ajkd.2021.07.018 . Epub 2021 Sep 9. PMID: 34508834. Hoppe B, Martin-Higueras C. Improving Treatment Options for Primary Hyperoxaluria. Drugs. 2022;82(10):1077–94. 10.1007/s40265-022-01735-x . Epub 2022 Jul 2. PMID: 35779234; PMCID: PMC9329168. Buades Fuster JM, Sanchís Cortés P, Perelló Bestard J, Grases Freixedas F. Plant phosphates, phytate and pathological calcifications in chronic kidney disease. Nefrologia 2017 Jan-Feb;37(1):20–8. 10.1016/j.nefro.2016.07.001 . Epub 2016 Sep 30. PMID: 27697413. Calvó P, Costa-Bauza A, Grases F. Effect of Phytate (InsP6) and Other Inositol-Phosphates (InsP5, InsP4, InsP3, InsP2) on Crystallization of Calcium Oxalate, Brushite, and Hydroxyapatite. Biomolecules. 2023;13(7):1061. 10.3390/biom13071061 . PMID: 37509097; PMCID: PMC10377479. Grases F, March JG, Prieto RM, Simonet BM, Costa-Bauzá A, García-Raja A, Conte A. Urinary phytate in calcium oxalate stone formers and healthy people–dietary effects on phytate excretion. Scand J Urol Nephrol. 2000;34(3):162-4. 10.1080/003655900750016526 . PMID: 10961468. Additional Declarations No competing interests reported. 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pH=6).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8468051/v1/f0d3f30a0a7e67418e68eb24.png"},{"id":106343403,"identity":"975dab3c-9968-47fb-a4f3-45e7ef9d267e","added_by":"auto","created_at":"2026-04-07 16:05:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1303641,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8468051/v1/36491256-7ee4-40df-bfca-addc0ec2a927.pdf"},{"id":100362024,"identity":"eac15df2-c637-4d39-8c2a-4ef94094a839","added_by":"auto","created_at":"2026-01-16 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While 24-hour urine oxalate measurements are standard, they can be unreliable in patients with normal kidney function due to incomplete acidification, crystal precipitation, or dietary influences.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Urine microscopy can detect high-density calcium oxalate monohydrate (COM) crystals, providing a sensitive and immediate clue for rare metabolic stone disorders.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e We report a case in which urine microscopy images led to the diagnosis of PH3, highlighting its educational value for nephrologists.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 31-year-old woman presented with intermittent flank discomfort and a history of recurrent nephrolithiasis since age 9. She had undergone left percutaneous nephrolithotomy at 18 and flexible ureteroscopy at 28. Serum creatinine was 0.8 mg/dL, and estimated glomerular filtration rate was \u0026gt;\u0026thinsp;90 mL/min/1.73 m\u0026sup2;.\u003c/p\u003e\n\u003cp\u003eUrine microscopy of first-morning specimens revealed abundant large COM crystals: 280/mm\u0026sup3; (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Fourier Transform Infrared spectroscopy of stones showed calcium phosphate (40%), calcium oxalate dihydrate (30%), and COM (30%). Two consecutive 24-hour urine collections showed isolated hyperoxaluria (45 and 72 mg/24 h, normal\u0026thinsp;\u0026lt;\u0026thinsp;45 mg/24 h) with normal calcium, citrate, and pH (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Genetic testing confirmed a homozygous HOGA1 splice-site mutation (c.700\u0026thinsp;+\u0026thinsp;5G\u0026thinsp;\u0026gt;\u0026thinsp;T), consistent with PH3.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eResults of 24-hour urine collections of the patient\u0026rsquo;s initial evaluation\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVolume mL/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eProtein mg/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUrea mmol/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCreatinine mg/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUric acid mmol/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCalcium mmol/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMagnesium mmol/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCitrate mg/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSodium mmol/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOxalate mg/24h\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOxalate mg/L\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNov\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDec\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1294\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e601\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eInitial conservative management included increased hydration (\u0026gt;\u0026thinsp;2 L/day), dietary calcium (1 g/day), and potassium citrate supplementation, which normalized urinary citrate, but crystalluria persisted after 14 months. Adjunctive phytate therapy (Lit-Control\u0026reg; pH Balance, 255 mg every 12 h) was introduced. Within several weeks, urine microscopy showed progressive reduction and eventual disappearance of COM crystals (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). During 24 months of follow-up, renal function remained stable, residual stones were unchanged, and no adverse effects were observed.\u003c/p\u003e\n\u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;margin-top:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003eTable 2\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e. Patient\u0026rsquo;s follow up and treatment\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"float: ;border: none;border-collapse: collapse;margin-left: 4.8pt;margin-right: 4.8pt;width: 551px;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.25pt;border-top: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);border-bottom: 1pt solid rgb(67, 67, 67);border-image: initial;border-left: none;padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e24h urine\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003eCItrate mg/24h\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84.75pt;border-top: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);border-bottom: 1pt solid rgb(67, 67, 67);border-image: initial;border-left: none;padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e24h urine\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003eOxalate mg/24\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.75pt;border-top: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);border-bottom: 1pt solid rgb(67, 67, 67);border-image: initial;border-left: none;padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003ePotassium citrate\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);border-bottom: 1pt solid rgb(67, 67, 67);border-image: initial;border-left: none;padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003eLit Control pH Balance\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89.25pt;border-top: 1pt solid rgb(67, 67, 67);border-right: 1pt solid rgb(67, 67, 67);border-bottom: 1pt solid rgb(67, 67, 67);border-image: initial;border-left: none;padding: 2pt;height: 26.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003eUrine Sediment Crystalluria\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.5pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;color:black;'\u003eMonth\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(243, 243, 243);padding: 2pt;height: 23.25pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.5pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e0\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e577\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e45\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan 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style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e69\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(217, 234, 211);padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;font-family:\"Segoe UI Symbol\",sans-serif;color:#EEF0FF;background:#1F1F1F;'\u003e✓\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp 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style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e20\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e586\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e50\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(217, 234, 211);padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;font-family:\"Segoe UI Symbol\",sans-serif;color:#EEF0FF;background:#1F1F1F;'\u003e✓\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;background: rgb(180, 198, 231);padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;font-family:\"Segoe UI Symbol\",sans-serif;color:#EEF0FF;background:#1F1F1F;'\u003e✓\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e+\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.5pt;border-right: 1pt solid black;border-bottom: 1pt solid black;border-left: 1pt solid black;border-image: initial;border-top: none;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-family:\"Calibri\",sans-serif;'\u003e25\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.25pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;line-height:normal;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:11px;font-family:\"Calibri\",sans-serif;'\u003e968\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84.75pt;border-top: none;border-left: none;border-bottom: 1pt solid black;border-right: 1pt solid black;padding: 2pt;height: 15.75pt;vertical-align: bottom;\"\u003e\n \u003cp 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style='font-family:\"Calibri\",sans-serif;'\u003e \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism, characterized by excessive endogenous oxalate production, recurrent nephrolithiasis, and progressive risk of renal impairment.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Three genetically distinct forms are recognized: PH1, PH2, and PH3. PH1 is the most common and carries the poorest prognosis, whereas PH2 and PH3 are less frequent and typically follow a milder course. PH3 results from biallelic mutations in HOGA1, which encodes 4-hydroxy-2-oxoglutarate aldolase, a mitochondrial enzyme expressed in the liver and kidney.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Loss-of-function mutations in HOGA1 lead to glyoxylate accumulation and subsequent oxalate overproduction. Our patient presented with childhood-onset, recurrent nephrolithiasis and was diagnosed with PH3 after genetic confirmation of the homozygous splice-site mutation c.700\u0026thinsp;+\u0026thinsp;5G\u0026thinsp;\u0026gt;\u0026thinsp;T, one of the most frequently reported HOGA1 variants in Europe.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough stone analysis revealed a mixed calcium oxalate and calcium phosphate composition, such findings are nonspecific and cannot differentiate PH3 from idiopathic stone disease, as mixed stones are common in PH2 and may occur in other conditions, including medullary sponge kidney, infection, or hyperparathyroidism.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eUrine microscopy played a critical role in diagnosis. Detection of \u0026gt;\u0026thinsp;200 calcium oxalate monohydrate (COM) crystals/mm\u0026sup3; is highly suggestive of primary hyperoxaluria and was particularly important when only one of two 24-hour urine oxalate measurements was elevated.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Urine sediment microscopy not only aids diagnosis but also provides real-time feedback on lithogenic activity, allowing clinicians to assess the impact of therapeutic interventions before new stones are detectable by imaging. Persistent crystalluria indicates ongoing stone formation, whereas its resolution signals successful suppression of lithogenesis, as observed in this patient. Calcium oxalate crystallization is the most frequent form of crystalluria in human urine due to the very low solubility of calcium oxalate. The type of crystal depends mainly on the urinary calcium-to-oxalate molar ratio.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e In hyperoxaluric conditions with normal or low calcium, the monohydrate form predominates, serving as a specific marker of hyperoxaluria, while the dihydrate form is less diagnostic.\u003c/p\u003e \u003cp\u003eUrine oxalate measurements are prone to pre-analytical variability, and plasma oxalate is informative only in kidney failure, rarely available, and not useful in this patient.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e While genetic testing provides a definitive diagnosis, it is costly, time-consuming, and not universally accessible; by contrast, urine microscopy is rapid, cost-effective, and widely available.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eManagement emphasizes urine dilution, citrate supplementation, and dietary calcium to reduce lithogenic risk .\u003csup\u003e1,5,6\u003c/sup\u003e In this patient, adjunctive phytate therapy coincided with disappearance of COM crystals, suggesting a potential role for crystallization inhibitors, though evidence remains limited, and phytate should not be considered primary therapy.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Phytate (inositol hexakisphosphate, InsP6) is a naturally occurring polyphosphate abundant in whole grains, legumes, nuts, and seeds.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e It inhibits nucleation, growth, and aggregation of calcium oxalate and phosphate crystals, a mechanism supported by experimental and clinical data.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e In our patient, supplementation with Lit-Control\u0026reg; pH Balance resulted in resolution of crystalluria, stabilization of stone burden, and preserved renal function over two years, highlighting its translational potential as an adjunctive therapy in PH3, where disease-specific treatments such as RNA interference are not established.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eStone removal should follow standard guidelines. Percutaneous nephrolithotomy is preferred for larger or complex stones, while extracorporeal shock wave lithotripsy may be considered selectively for smaller stones.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eUrine microscopy provided the critical visual clue leading to the diagnosis of a rare metabolic disorder. High-density COM crystalluria complements urinary oxalate measurements and offers a rapid, inexpensive diagnostic approach, particularly in patients with normal kidney function. Conservative therapy with hydration, citrate, and dietary calcium remains the mainstay of management, and adjunctive measures such as phytate may further reduce lithogenic risk. This case highlights the importance of integrating urine microscopy into routine evaluation of patients with recurrent nephrolithiasis.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eWritten informed consent for publication of this case report and accompanying images was obtained from the patient. The authors confirm responsibility for the integrity and accuracy of the data and for the decision to submit the manuscript for publication.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eContributionsDS \u0026ndash; literature search, clinical data acquisition, data analysis, and manuscript drafting, editing, and review.MBL\u0026ndash; clinical data acquisition and manuscript preparation, editing, and review.DN \u0026ndash; manuscript review.PB \u0026ndash; manuscript review.CJ \u0026ndash; manuscript review.LCP \u0026ndash; manuscript review.NMF \u0026ndash; concept, study design, definition of intellectual content, manuscript editing, and critical manuscript review.All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this published article. Additional data are available from the corresponding author on reasonable request.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGroothoff JW, Metry E, Deesker L, Garrelfs S, Acquaviva C, Almardini R, Beck BB, Boyer O, Cerkauskiene R, Ferraro PM, Groen LA, Gupta A, Knebelmann B, Mandrile G, Moochhala SS, Prytula A, Putnik J, Rumsby G, Soliman NA, Somani B, Bacchetta J. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023;19(3):194\u0026ndash;211. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41581-022-00661-1\u003c/span\u003e\u003cspan address=\"10.1038/s41581-022-00661-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2023 Jan 5. PMID: 36604599.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaudon M, Bouzidi H, Bazin D. Composition and morphology of phosphate stones and their relation with etiology. Urol Res. 2010;38(6):459\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaudon M, Crystalluria. A marker for diagnosis and prognosis of crystallogenic pathologies and nephrolithiasis. Rev Fr Lab. 2013;455:67\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaudon M, Letavernier E, Frochot V, Haymann JP, Bazin D, Jungers P. Respective influence of calcium and oxalate urine concentration on the formation of calcium oxalate monohydrate or dihydrate crystals. C R Chim. 2016;19(11\u0026ndash;12):1504\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkolarikos A, Somani B, Neisius A, Jung H, Petř\u0026iacute;k A, Tailly T, Davis N, Tzelves L, Geraghty R, Lombardo R, Bezuidenhout C, Gambaro G. Metabolic Evaluation and Recurrence Prevention for Urinary Stone Patients: An EAU Guidelines Update. Eur Urol. 2024;86(4):343\u0026ndash;63. Epub 2024 Jul 27. PMID: 39069389.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemoulin N, Aydin S, Gillion V, Morelle J, Jadoul M. Pathophysiology and Management of Hyperoxaluria and Oxalate Nephropathy: A Review. Am J Kidney Dis. 2022;79(5):717\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.ajkd.2021.07.018\u003c/span\u003e\u003cspan address=\"10.1053/j.ajkd.2021.07.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Sep 9. PMID: 34508834.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoppe B, Martin-Higueras C. Improving Treatment Options for Primary Hyperoxaluria. Drugs. 2022;82(10):1077\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40265-022-01735-x\u003c/span\u003e\u003cspan address=\"10.1007/s40265-022-01735-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2022 Jul 2. PMID: 35779234; PMCID: PMC9329168.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuades Fuster JM, Sanch\u0026iacute;s Cort\u0026eacute;s P, Perell\u0026oacute; Bestard J, Grases Freixedas F. Plant phosphates, phytate and pathological calcifications in chronic kidney disease. Nefrologia 2017 Jan-Feb;37(1):20\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nefro.2016.07.001\u003c/span\u003e\u003cspan address=\"10.1016/j.nefro.2016.07.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Sep 30. PMID: 27697413.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalv\u0026oacute; P, Costa-Bauza A, Grases F. Effect of Phytate (InsP6) and Other Inositol-Phosphates (InsP5, InsP4, InsP3, InsP2) on Crystallization of Calcium Oxalate, Brushite, and Hydroxyapatite. Biomolecules. 2023;13(7):1061. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/biom13071061\u003c/span\u003e\u003cspan address=\"10.3390/biom13071061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 37509097; PMCID: PMC10377479.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrases F, March JG, Prieto RM, Simonet BM, Costa-Bauz\u0026aacute; A, Garc\u0026iacute;a-Raja A, Conte A. Urinary phytate in calcium oxalate stone formers and healthy people\u0026ndash;dietary effects on phytate excretion. Scand J Urol Nephrol. 2000;34(3):162-4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/003655900750016526\u003c/span\u003e\u003cspan address=\"10.1080/003655900750016526\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 10961468.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Primary hyperoxaluria, Urine microscopy, crystalluria, Nephrolithiasis, case report","lastPublishedDoi":"10.21203/rs.3.rs-8468051/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8468051/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePrimary hyperoxaluria type 3 is a rare autosomal recessive disorder caused by HOGA1 mutations, leading to recurrent calcium oxalate nephrolithiasis. Diagnosis is often delayed, and 24-hour urine oxalate measurements can be unreliable in patients with normal kidney function. Urine microscopy can detect high-density calcium oxalate monohydrate crystals, providing a rapid diagnostic clue.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCase Presentation\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA 31-year-old woman with recurrent nephrolithiasis since age 9 had undergone prior percutaneous nephrolithotomy and ureteroscopy. Urine microscopy revealed abundant COM crystals (280/mm\u0026sup3;), and stone analysis showed mixed calcium phosphate, oxalate dihydrate, and COM. Genetic testing confirmed homozygous HOGA1 mutation (c.700\u0026thinsp;+\u0026thinsp;5G\u0026thinsp;\u0026gt;\u0026thinsp;T). Conservative management with hydration, dietary calcium, and potassium citrate normalized citrate but not crystalluria. Adjunctive phytate therapy led to disappearance of calcium oxalate monohydrate crystals within weeks. Renal function and residual stones remained stable over 24 months.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDetection of \u0026gt;\u0026thinsp;200 calcium oxalate monohydratecrystals/mm\u0026sup3; is highly suggestive of PH3. Urine microscopy is rapid, inexpensive, and complements genetic testing. Conservative therapy remains central, and adjunctive measures like phytate may help reduce crystallization risk.\u003c/p\u003e","manuscriptTitle":"Urine Microscopy Revealing a Metabolic Disorder: a Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:23:45","doi":"10.21203/rs.3.rs-8468051/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-30T15:27:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-30T09:37:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158359633155640693791518687311346562519","date":"2026-01-29T18:50:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"83678406550666186512748638130895452610","date":"2026-01-29T08:14:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181890450578408716740224001844303642847","date":"2026-01-28T18:51:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108977460048363351328656465662776471374","date":"2026-01-28T18:19:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-28T15:35:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"33906901982900214282257206452051246354","date":"2026-01-28T09:56:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204052584148706481816226811665261381063","date":"2026-01-27T21:08:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-27T10:14:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"61244190041655569638046637226997976846","date":"2026-01-27T10:01:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124876365564581417302748364014930895547","date":"2026-01-26T16:34:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306655247304010628546778580561313852414","date":"2026-01-26T16:19:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"239826301067057424213210229933489838832","date":"2026-01-17T06:49:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-07T20:28:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T14:28:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-06T21:18:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-01-06T21:13:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5317ebd0-e811-4f89-89e3-90c5c078365f","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T16:02:06+00:00","versionOfRecord":{"articleIdentity":"rs-8468051","link":"https://doi.org/10.1186/s12882-026-04946-6","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2026-03-31 15:57:59","publishedOnDateReadable":"March 31st, 2026"},"versionCreatedAt":"2026-01-12 06:23:45","video":"","vorDoi":"10.1186/s12882-026-04946-6","vorDoiUrl":"https://doi.org/10.1186/s12882-026-04946-6","workflowStages":[]},"version":"v1","identity":"rs-8468051","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8468051","identity":"rs-8468051","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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