Hipocytraturia – znaczenie w rozwoju kamicy układu moczowego

• Authors: Piotr Skrzypczyk , Małgorzata Pańczyk-Tomaszewska

Title variants

EN

Hypocitraturia: its importance as a factor in the development of urolithiasis

• Languages of publication: PL EN

Abstracts

PL

Anion cytrynianowy to endogenny inhibitor powstawania złogów wapniowych w drogach moczowych. Ponadto przez alkalizację moczu cytryniany zwiększają rozpuszczalność kwasu moczowego i cystyny. Hipocytraturia definiowana jest u dorosłych jako wydalanie cytrynianów z moczem poniżej 320 mg/24 h. Najczęściej stosowane definicje hipocytraturii u dzieci to wydalanie cytrynianów w dobowej zbiórce moczu <365 mg/1,73 m2/24 h u chłopców i <310 mg/1,73 m2/24 h u dziewczynek; używa się też wskaźnika cytrynianowo-kreatyninowego z porcji moczu: dla dzieci w wieku 0–5 lat <0,42 mg/mg, a powyżej 5. roku życia: <0,25 mg/mg. Hipocytraturia to częsta nieprawidłowość metaboliczna – stwierdza się ją u około 20–60% dorosłych i 10–68% dzieci z kamicą. Na wydalanie cytrynianów z moczem wpływ ma wiele czynników, z których najważniejszym jest wartość pH (krwi, moczu oraz wewnątrzkomórkowe). Większość pacjentów ma tzw. idiopatyczną hipocytraturię, choć występuje ona także w stanach kwasicy, w tym kwasicy kanalikowej dystalnej, hipokaliemii, diecie bogatobiałkowej oraz przy stosowaniu niektórych leków (inhibitory anhydrazy węglanowej, inhibitory konwertazy angiotensyny, diuretyki tiazydowe). U pacjentów z hipocytraturią w pierwszej kolejności należy podjąć modyfikacje dietetyczne, polegające na zwiększeniu ilości przyjmowanych płynów i owoców cytrusowych oraz ograniczeniu spożycia soli i białka. U pacjentów z nawrotową kamicą zastosowanie znajdują preparaty cytrynianów, z których najczęściej stosuje się cytrynian potasu. Alternatywnie można stosować soki cytrusowe, jednak ich korzystne działanie nie jest tak silne i jednoznaczne jak w przypadku komercyjnie dostępnych preparatów cytrynianów.

EN

The citrate anion is an endogenous inhibitor of calcium deposits in the urinary tract. Moreover, by urine alkalisation, citrates enhance uric acid and cystine solubility. Hypocitraturia in adults is defined as excretion of citrates with urine below 320 mg/24 h. The most common definitions in children involve citrate excretion in 24 hour urine collection at a level <365 mg/1.73 m2/24 h in boys and <310 mg/1.73 m2/24 h in girls. Moreover, the urine citrate/creatinine ratio is also considered: for children aged 0–5 years <0.42 mg/mg and for children older than 5 years of age <0.25 mg/mg. Hypocitraturia is a common metabolic disturbance; such a diagnosis is made in approximately 20–60% of adults and 10–68% of children with urolithiasis. Various factors may affect citrate excretion with urine, the most significant of which is the pH value (of blood, urine or intracellular fluid). Most patients are diagnosed with so-called idiopathic hypocitraturia, although it also accompanies acidosis, including distal tubular acidosis, hypokalaemia, high-protein diet and treatment with certain medications (carbonic anhydrase inhibitors, angiotensin-converting enzyme inhibitors, thiazide diuretics). Patients with hypocitraturia should first and of foremost have dietary modifications introduced. This involves an increase in the dietary amount of fluids and citrus fruit as well as salt and protein restriction. Patients with recurring urolithiasis may also be recommended citrate products, the most common of which is potassium citrate. Citrus juices may be an alternative, but their effect is not as potent and unambiguous as in the case of commercially available citrate products.

Keywords

EN

cytryniany; dzieci; hipocytraturia; kamica moczowa

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Pediatria i Medycyna Rodzinna
• Year: 2019
• Volume: 15
• Issue: 1
• Pages: 26–32

Contributors

author

Piotr Skrzypczyk

• Katedra i Klinika Pediatrii i Nefrologii, Warszawski Uniwersytet Medyczny, Warszawa, Polska

author

Małgorzata Pańczyk-Tomaszewska

• Katedra i Klinika Pediatrii i Nefrologii, Warszawski Uniwersytet Medyczny, Warszawa, Polska

References

• Rudman D, Kutner MH, Redd SC 2nd et al.: Hypocitraturia in calcium nephrolithiasis. J Clin Endocrinol Metab 1982; 55: 1052–1057.
• Pak CY: Etiology and treatment of urolithiasis. Am J Kidney Dis 1991; 18: 624–637.
• Miller LA, Stapleton FB: Urinary citrate excretion in children with hypercalciuria. J Pediatr 1985; 107: 263–266.
• Gouru VR, Pogula VR, Vaddi SP et al.: Metabolic evaluation of children with urolithiasis. Urol Ann 2018; 10: 94–99.
• Bevill M, Kattula A, Cooper CS et al.: The modern metabolic stone evaluation in children. Urology 2017; 101: 15–20.
• Spivacow FR, Del Valle EE, Rey PG: Metabolic risk factors in children with asymptomatic hematuria. Pediatr Nephrol 2016; 31: 1101–1106.
• Kovacevic L, Wolfe-Christensen C, Edwards L et al.: From hypercalciuria to hypocitraturia – a shifting trend in pediatric urolithiasis? J Urol 2012; 188 (Suppl): 1623–1627.
• Hoppe B, Kemper MJ: Diagnostic examination of the child with urolithiasis or nephrocalcinosis. Pediatr Nephrol 2010; 25: 403–413.
• Sikora P, Roth B, Kribs A et al.: Hypocitraturia is one of the major risk factors for nephrocalcinosis in very low birth weight (VLBW) infants. Kidney Int 2003; 63: 2194–2199.
• López M, Hoppe B: History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol 2010; 25: 49–59.
• Chow K, Dixon J, Gilpin S et al.: Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones. Kidney Int 2004; 65: 1724–1730.
• Curhan GC, Taylor EN: 24-h uric acid excretion and the risk of kidney stones. Kidney Int 2008; 73: 489–496.
• Kirejczyk JK, Porowski T, Konstantynowicz J et al.: Urinary citrate excretion in healthy children depends on age and gender. Pediatr Nephrol 2014; 29: 1575–1582.
• DeFoor W, Jackson E, Schulte M et al.: Calcium-to-citrate ratio distinguishes solitary and recurrent urinary stone forming children. J Urol 2017; 198: 416–421.
• Turudic D, Batinic D, Golubic AT et al.: Calcium oxalate urolithiasis in children: urinary promoters/inhibitors and role of their ratios. Eur J Pediatr 2016; 175: 1959–1965.
• Krebs HA, Salvin E, Johnson WA: The formation of citric and alpha-ketoglutaric acids in the mammalian body. Biochem J 1983; 32: 113–117.
• Costello LC, Franklin RB: Plasma citrate homeostasis: how it is regulated; and its physiological and clinical implications. An important, but neglected, relationship in medicine. HSOA J Hum Endocrinol 2016; 1: 1–19.
• Brennan TS, Klahr S, Hamm LL: Citrate transport in rabbit nephron. Am J Physiol 1986; 251: 683–689.
• Simpson DP: Citrate excretion: a window on renal metabolism. Am J Physiol 1983; 244: 223–234.
• Melnick JZ, Srere PA, Elshourbagy NA et al.: Adenosine triphosphate citrate lyase mediates hypocitraturia in rats. J Clin Invest 1996; 98: 2381–2387.
• Dedmon RE, Wrong O: The excretion of organic anion in renal tubular acidosis with particular reference to citrate. Clin Sci 1962; 22: 19–32.
• Kok DJ, Papapoulos SE, Bijvoet OL: Crystal agglomeration is a major element in calcium oxalate urinary stone formation. Kidney Int 1990; 37: 51–56.
• Sheng X, Jung T, Wesson JA et al.: Adhesion at calcium oxalate crystal surfaces and the effect of urinary constituents. Proc Natl Acad Sci U S A 2005; 102: 267–272.
• Hess B, Zipperle L, Jaeger P: Citrate and calcium effects on Tamm–Horsfall glycoprotein as a modifier of calcium oxalate crystal aggregation. Am J Physiol 1993; 265: 784–791.
• Habbig S, Beck BB, Hoppe B: Nephrocalcinosis and urolithiasis in children. Kidney Int 2011; 80: 1278–1291.
• Mandel EI, Taylor EN, Curhan GC: Dietary and lifestyle factors and medical conditions associated with urinary citrate excretion. Clin J Am Soc Nephrol 2013; 8: 901–908.
• Reddy ST, Wang CY, Sakhaee K et al.: Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 2002; 40: 265–274.
• Domrongkitchaiporn S, Stitchantrakul W, Kochakarn W: Causes of hypocitraturia in recurrent calcium stone formers: focusing on urinary potassium excretion. Am J Kidney Dis 2006; 48: 546–554.
• Sakhaee K, Harvey JA, Padalino PK et al.: The potential role of salt abuse on the risk for kidney stone formation. J Urol 1993; 150: 310–312.
• Windus DW, Cohn DE, Heifets M: Effects of fasting on citrate transport by the brush-border membrane of rat kidney. Am J Physiol 1986; 251: 678–682.
• Mossetti G, Vuotto P, Rendina D et al.: Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis. J Intern Med 2003; 253: 194–200.
• Pajor AM, Sun N: Protein kinase C-mediated regulation of the renal Na+/dicarboxylate cotransporter, NaDC-1. Biochim Biophys Acta 1999; 1420: 223–230.
• Okamoto N, Aruga S, Matsuzaki S et al.: Associations between renal sodium-citrate cotransporter (hNaDC-1) gene polymorphism and urinary citrate excretion in recurrent renal calcium stone formers and normal controls. Int J Urol 2007; 14: 344–349.
• Medina-Escobedo M, González-Herrera L, Villanueva-Jorge S et al. Metabolic abnormalities and polymorphisms of the vitamin D receptor (VDR) and ZNF365 genes in children with urolithiasis. Urolithiasis 2014; 42: 395–400.
• Pak CY: Citrate and renal calculi: an update. Miner Electrolyte Metab 1994; 20: 371–377
• Welch BJ, Graybeal D, Moe OW et al.: Biochemical and stonerisk profiles with topiramate treatment. Am J Kidney Dis 2006; 48: 555–563.
• Hamm LL: Renal handling of citrate. Kidney Int 1990; 38: 728–735.
• Reungjui S, Prasongwatana V, Premgamone A et al.: Magnesium status of patients with renal stones and its effect on urinary citrate excretion. BJU Int 2002; 90: 635–639.
• Koff SG, Paquette EL, Cullen J et al.: Comparison between lemonade and potassium citrate and impact on urine pH and 24-hour urine parameters in patients with kidney stone formation. Urology 2007; 69: 1013–1016.
• Alvarez-Arroyo MV, Traba ML, Rapado A et al.: Role of citric acid in primary hyperparathyroidism with renal lithiasis. Urol Res 1992; 20: 88–90.
• Franklin R, Costello LC, Stacey R et al.: Calcitonin effects on plasma and urinary citrate levels in rats. Am J Physiol. 1973; 225: 1178–1180.
• Corbin Bush N, Twombley K, Ahn J et al.: Prevalence and spot urine risk factors for renal stones in children taking topiramate. J Pediatr Urol 2013; 9: 884–889.
• Melnick JZ, Preisig PA, Haynes S et al.: Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia. Kidney Int 1998; 54: 1670–1674.
• Pak CY, Peterson R, Sakhaee K et al.: Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis. Am J Med 1985; 79: 284–288.
• Zhang X, Aggarwal P, Li X et al.: The role of lithium carbonate and lithium citrate in regulating urinary citrate level and preventing nephrolithiasis. Int J Biomed Sci 2009; 5: 215–222.
• Marangella M, Vitale C, Manganaro M et al.: Renal handling of citrate in chronic renal insufficiency. Nephron 1991; 57: 439–443.
• Shey J, Cameron MA, Sakhaee K et al.: Recurrent calcium nephrolithiasis associated with primary aldosteronism. Am J Kidney Dis 2004; 44: 7–12.
• Cochat P, Pichault V, Bacchetta J et al.: Nephrolithiasis related to inborn metabolic diseases. Pediatr Nephrol 2010; 25: 415–424.
• Ekeruo WO, Tan YH, Young MD et al.: Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients. J Urol 2004; 172: 159–163.
• Sakhaee K, Nigam S, Snell P et al.: Assessment of the pathogenetic role of physical exercise in renal stone formation. J Clin Endocrinol Metab 1987; 65: 974–979.
• Meschi T, Maggiore U, Fiaccadori E et al.: The effect of fruits and vegetables on urinary stone risk factors. Kidney Int 2004; 66: 2402–2410.
• Pak CY, Fuller C: Idiopathic hypocitraturic calcium-oxalate nephrolithiasis successfully treated with potassium citrate. Ann Intern Med 1986; 104: 33–37.
• Cicerello E, Merlo F, Gambaro G et al.: Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J Urol 1994; 151: 5–9.
• Hofbauer J, Höbarth K, Szabo N et al.: Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis – a prospective randomized study. Br J Urol 1994; 73: 362–365.
• Soygür T, Akbay A, Küpeli S: Effect of potassium citrate therapy on stone recurrence and residual fragments after shockwave lithotripsy in lower caliceal calcium oxalate urolithiasis: a randomized controlled trial. J Endourol 2002; 16: 149–152.
• Karsli O, Izol V, Aridogan IA et al.: Metabolic risk factors and the effect of metaphylaxis in pediatric stone disease with hypocitraturia. Urolithiasis 2013; 41: 9–13.
• Mattle D, Hess B: Preventive treatment of nephrolithiasis with alkali citrate – a critical review. Urol Res 2005; 33: 73–79.
• Wabner CL, Pak CY: Effect of orange juice consumption on urinary stone risk factors. J Urol 1993; 149: 1405–1408.
• Goldfarb DS, Asplin JR: Effect of grapefruit juice on urinary lithogenicity. J Urol 2001; 166: 263–267.
• Penniston KL, Steele TH, Nakada SY: Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology 2007; 70: 856–860.
• Zuckerman JM, Assimos DG: Hypocitraturia: pathophysiology and medical management. Rev Urol 2009; 11: 134–144.
• Granner DK, Murray RK, Rodwell VW: Biochemia Harpera Ilustrowana. Wydawnictwo Lekarskie PZWL, Warszawa 2018.

• Document Type: article