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The Causes of Uric Acid Stones and Preventative Treatment





Accurate diagnosis is crucial for identifying the underlying cause of uric acid stones, which is essential for effective treatment and prevention. Uric acid stones are broadly classified into three categories: idiopathic, secondary, and congenital.¹ ²



Idiopathic Uric Acid Stones (Most Common Form)


This category represents the majority of uric acid stone cases, where the exact cause is often difficult to pinpoint. However, two primary factors are commonly associated:


  • Persistent Aciduria (Low Urine pH): Aciduria, characterized by consistently low urine pH, plays a central role in uric acid stone formation. This can arise from two primary mechanisms:

    • Increased Endogenous Acid Production: The body produces an excessive amount of acid, overwhelming its buffering capacity. This can be influenced by dietary factors, metabolic conditions, or inherent variations in acid production.

    • Inadequate Buffering Capacity: The kidneys' ability to neutralize acid in the urine is compromised. This may be due to reduced production or excretion of buffers like bicarbonate, phosphate, or citrate.³ ⁴

  • Insulin Resistance: This metabolic derangement, often linked to obesity, metabolic syndrome, and type 2 diabetes mellitus, significantly increases the risk of uric acid stone formation. Insulin resistance promotes acid production, reduces urinary pH, and may increase urate excretion.⁵ ⁶ ⁷



Secondary Uric Acid Stones

These stones form as a consequence of other underlying medical conditions or external factors:


  • High Purine Intake: Diets rich in purines, found abundantly in red meat, organ meats, and certain seafood, can lead to overproduction of uric acid, exceeding the kidneys' capacity to excrete it.

  • Gout: This inflammatory arthritis is characterized by hyperuricemia (elevated uric acid levels in the blood). The excess uric acid can precipitate in the joints, causing painful inflammation, and can also lead to increased uric acid excretion in the urine.

  • Gastrointestinal (GI) Losses: Significant fluid and alkali losses from the GI tract can concentrate the urine and lower its pH. This can occur in several situations:

    • Chronic Diarrhea: Conditions causing persistent diarrhea, such as irritable bowel syndrome (IBS), ileostomies, colostomies, short bowel syndrome (often after surgical resection), and certain malabsorptive disorders, can lead to substantial fluid and bicarbonate losses.⁸ ⁹ ¹⁰

    • Malabsorption Syndromes: Any condition causing fat malabsorption, including pancreatic insufficiency and bile acid disorders, can indirectly contribute to uric acid and oxalate stone formation.¹¹

  • High Cell Turnover: Rapid breakdown of cells, as seen in certain medical conditions, releases large amounts of purines into the bloodstream. These purines are metabolized into uric acid, potentially overwhelming the kidneys' excretory capacity. Examples include:

    • Hematologic Malignancies: Leukemia, lymphoma, and other cancers with rapid cell proliferation.

    • Chemotherapy: Treatment of cancers can cause massive tumor cell lysis, releasing large amounts of uric acid.

    • Hemolytic Anemias: Conditions causing excessive destruction of red blood cells.

    • Necrotizing Diseases: Severe tissue injury leading to cell death.

  • Certain Medications: Some medications can increase uric acid production or decrease its excretion, increasing the risk of stone formation.¹² Examples include:

    • Loop Diuretics: These diuretics, such as furosemide, can increase uric acid reabsorption in the kidneys.

    • Low-Dose Aspirin: While high-dose aspirin promotes uric acid excretion, low doses can have the opposite effect.

    • Certain Chemotherapy Drugs: Some chemotherapy agents can lead to tumor lysis syndrome and subsequent uric acid nephropathy.

    • Calcineurin Inhibitors: Cyclosporine and tacrolimus, used as immunosuppressants, can increase uric acid levels.

    • Important Note: Patients should never discontinue any prescribed medication without consulting their physician.



Congenital Causes of Uric Acid Stones


These are rare, inherited genetic disorders that disrupt uric acid metabolism:

  • Inborn Errors of Metabolism: Several genetic conditions can lead to overproduction or underexcretion of uric acid, including:¹²

    • Lesch-Nyhan Syndrome: A rare X-linked disorder characterized by severe hyperuricemia, gout, neurological problems, and self-injurious behavior.

    • Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) Deficiency: A less severe variant of Lesch-Nyhan syndrome.

    • Phosphoribosylpyrophosphate Synthetase (PRPS) Superactivity: Leads to overproduction of purines and uric acid.

    • Familial Renal Uric Acid Leak: Impaired reabsorption of uric acid in the kidneys, leading to excessive uric acid excretion and increased risk of stone formation. ¹²


Preventative Medical Interventions


Effective management of uric acid stones relies on identifying the underlying cause and tailoring treatment accordingly.

  • Idiopathic Cases: Treatment primarily focuses on:

    • Urine Alkalinization: Increasing urine pH to dissolve existing uric acid stones and prevent new ones from forming. This is typically achieved with oral potassium citrate or sodium bicarbonate.

    • Management of Insulin Resistance: Lifestyle modifications, including weight loss, regular exercise, and dietary changes, are crucial. Medications to improve insulin sensitivity may also be effective.¹⁵

  • Secondary Cases: Treatment addresses the underlying condition contributing to uric acid stone formation. This may involve dietary modifications, medication adjustments, management of gout, treatment of GI disorders, or other interventions.

  • Congenital Cases: Management focuses on reducing uric acid levels through medication (e.g., allopurinol) and supportive care.



Preventative Dietary Interventions


Dietary modifications play a significant role in both preventing and treating uric acid stones:

  • Increase Fluid Intake: Adequate hydration dilutes the urine, reducing the concentration of uric acid and other minerals, thus lowering the risk of stone formation.

  • Limit Purine Intake: Reduce consumption of high-purine foods, such as red meat, organ meats, and certain seafood.

  • Increase Consumption of Fruits and Vegetables: These foods are generally low in purines and can help to alkalinize the urine.¹³ ¹⁴

  • Moderate Protein Intake: Excessive protein intake can increase urine pH.¹³ ¹⁴

  • Limit Alcohol Consumption: Alcohol can interfere with uric acid excretion and promote dehydration.

  • Maintain a Healthy Weight: Weight loss can improve insulin sensitivity and reduce the risk of uric acid stones.


References:

 

1.      Ma Q, Fang L, Su R, Ma L, Xie G, Cheng Y. Uric acid stones, clinical manifestations and therapeutic considerations. Postgrad Med J. 2018 Aug;94(1114):458-462. 

2.      Shen X, Pan Q, Huang Y, You J, Chen Y, Ding X. Metabolic Syndrome Predicts Uric Acid Stones in the Upper Urinary Tract: Development and Validation of a Nomogram Model. Arch Esp Urol. 2023 Jun;76(4):255-263. 

3.      Tran TVM, Maalouf NM. Uric acid stone disease: lessons from recent human physiologic studies. Curr Opin Nephrol Hypertens. 2020 Jul;29(4):407-413.

4.      Maalouf NM, Cameron MA, Moe OW, et al. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens 2004; 13: 181.

5.      Abate N, Chandalia M, Cabo-Chan AV Jr, Moe OW, Sakhaee K. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int. 2004;65(2):386–92. 

6.      Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Metabolic basis for low urine pH in type 2 diabetes. Clin J Am Soc Nephrol. 2010 Jul;5(7):1277–81.

7.      Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422–8.

8.      Sakhaee K, Williams RH, Oh MS, Padalino P, Adams-Huet B, Whitson P, Pak CY. Alkali absorption and citrate excretion in calcium nephrolithiasis. J Bone Miner Res. 1993 Jul;8(7):789-94

9.      7. Rudman D, Dedonis JL, Fountain MT, et al. Hypocitraturia in patients with gastrointestinal malabsorption. N Engl J Med. 1980;303:657–661.

10. Usui Y, Matsuzaki S, Matsushita K, Shima M. Urinary citrate in kidney stone disease. Tokai J Exp Clin Med. 2003;28:65–70.

11. Moe OW, Xu LHR. Hyperuricosuric calcium urolithiasis. J Nephrol. 2018 Apr;31(2):189-196. 

12. Manish KC, Leslie SW. Uric acid nephrolithiasis. 2023 Oct 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan

13. Wiederkehr MR, Moe OW. Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder. Clin Rev Bone Miner Metab. 2011 Dec;9(3-4):207-217.

14.  Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA Guideline. J Urology. 2014; 192;316-324.

15. Maalouf NM, Poindexter JR, Adams-Huet B, Moe OW, Sakhaee K. Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone. Kidney Int. 2019 May;95(5):1262-1268.

 
 
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