Urolithiasis

, Volume 44, Issue 1, pp 65–76 | Cite as

How should patients with cystine stone disease be evaluated and treated in the twenty-first century?

  • Kim Hovgaard Andreassen
  • Katja Venborg Pedersen
  • Susanne Sloth Osther
  • Helene Ulrik Jung
  • Søren Kissow Lildal
  • Palle Joern Sloth Osther
Invited Review

Abstract

Cystinuria continues to be one of the most challenging stone diseases. During the latest decades our knowledge of the molecular basis of cystinuria has expanded. Today 160 different mutations in the SLC3A1 gene and 116 in the SLC7A9 gene are listed. The full implications of type A, B or AB status are not yet fully understood but may have implications for prognosis, management and treatment. Despite better understanding of the molecular basis of cystinuria the principles of recurrence prevention have remained essentially the same through decades. No curative treatment of cystinuria exists, and patients will have a life long risk of stone formation, repeated surgery, impaired renal function and quality of life. Therapy to reduce stone formation is directed towards lowering urine cystine concentration and increasing cystine solubility. Different molecules that could play a role in promoting nucleation and have a modulating effect on cystine solubility may represent new targets for cystinuria research. Investigation of newer thiol-containing drugs with fewer adverse effects is also warranted. Determining cystine capacity may be an effective tool to monitor the individual patient’s response. Compliance in cystinuric patients concerning both dietary and pharmacological intervention is poor. Frequent clinical follow-up visits in dedicated centres seem to improve compliance. Cystinuric patients should be managed in dedicated centres offering the complete range of minimal invasive treatment modalities, enabling a personalized treatment approach in order to reduce risk and morbidity of multiple procedures.

Keywords

Cystinuria Kidney stones Nephrolithiasis Urolithiasis Genetic Prevention Pharmacologic therapy Surgical therapy 

References

  1. 1.
    Chillaron J, Font-Llitjos M, Fort J, Zorzano A, Goldfarb DS, Nunes V, Palacin M (2010) Pathophysiology and treatment of cystinuria. Nat Rev Nephrol 6:424–434PubMedCrossRefGoogle Scholar
  2. 2.
    Thomas K, Wong K, Withington J, Bultitude M, Doherty A (2014) Cystinuria—a urologist’s perspective. Nat Rev Urol 11:270–277PubMedCrossRefGoogle Scholar
  3. 3.
    Faerber GJ (2001) Pediatric urolithiasis. Curr Opin Urol 11:385–389PubMedCrossRefGoogle Scholar
  4. 4.
    Claes DJ, Jackson E (2012) Cystinuria: mechanisms and management. Pediatr Nephrol 27:2031–2038PubMedCrossRefGoogle Scholar
  5. 5.
    Elmaci AM, Ece A, Akin F (2014) Pediatric urolithiasis: metabolic risk factors and follow-up results in a Turkish region with endemic stone disease. Urolithiasis 42:421–426PubMedCrossRefGoogle Scholar
  6. 6.
    Leusmann DB, Blaschke R, Schmandt W (1990) Results of 5,035 stone analyses: a contribution to epidemiology of urinary stone disease. Scand J Urol Nephrol 24:205–210PubMedCrossRefGoogle Scholar
  7. 7.
    Polinsky MS, Kaiser BA, Baluarte HJ (1987) Urolithiasis in childhood. Pediatr Clin North Am 34:683–710PubMedGoogle Scholar
  8. 8.
    Knoll T, Zöllner A, Wendt-Nordahl G, Michel MS, Alken P (2005) Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol 20:19–24PubMedCrossRefGoogle Scholar
  9. 9.
    Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM number: 104614 and 604144. http://omim.org/entry/220100. Accessed 30 April 2015
  10. 10.
    Krombach P, Knoll GW-N (2011) Cystinuria and Cystine Stones. In: Rao PN, Kavanagh JP, Preminger GM (eds) Urinary Tract Stone Disease. Springer-Verlag, LondonGoogle Scholar
  11. 11.
    Dello Strologo L, Pras E, Pontesilli C, Beccia E, Ricci-Barbini V, de Sanctis L, Ponzone A, Gallucci M, Bisceglia L, Zelante L, Jimenez-Vidal M, Font M, Zorzano A, Rousaud F, Nunes V, Gasparini P, Palacín M, Rizzoni G (2002) Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J Am Soc Nephrol 13:2547–2553PubMedCrossRefGoogle Scholar
  12. 12.
    Saravakos P, Kokkinou V, Giannatos E (2014) Cystinuria: current diagnosis and management. Urology 83:693–699PubMedCrossRefGoogle Scholar
  13. 13.
    Eggermann T, Venghaus A, Zerres K (2012) Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis 7:19PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Eggermann T, Zerres K, Nunes V, Font-Llitjós M, Bisceglia L, Chatzikyriakidou A, dello Strologo L, Pras E, Creemers J, Palacin M (2012) Clinical utility gene card for: cystinuria. Eur J Hum Genet 20(2). doi:10.1038/ejhg.2011.163
  15. 15.
    Font-Llitjós M, Jiménez-Vidal M, Bisceglia L, Di Perna M, de Sanctis L, Rousaud F, Zelante L, Palacín M, Nunes V (2005) New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype. J Med Genet 42:58–68PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Wong KA, Mein R, Wass M, Flinter F, Pardy C, Bultitude M, Thomas K (2015) The genetic diversity of Cystinuria in a UK population of patients. BJU Int 116(1):109–116. doi:10.1111/bju.12894 PubMedCrossRefGoogle Scholar
  17. 17.
    Popovska-Jankovic K, Tasic V, Bogdanovic R, Miljkovic P, Golubovic E, Soylu A, Saraga M, Pavicevic S, Baskin E, Akil I, Gregoric A, Lilova M, Topaloglu R, Sukarova Stefanovska E, Plaseska-Karanfilska D (2013) Molecular characterization of cystinuria in south-eastern European countries. Urolithiasis 41:21–30.doi:10.1111/bju.12894 PubMedCrossRefGoogle Scholar
  18. 18.
    Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, Mota M, Dias C, Rodrigues-Santos P, Fortuna AM, Quelhas D, Lacerda L, Bisceglia L, Cardoso ML (2012) Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients. Clin Genet 81:47–55PubMedCrossRefGoogle Scholar
  19. 19.
    Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, Wassner AJ, Nelson CP, Tasic V, Sayer JA, Hildebrandt F (2015) Fourteen monogenic genes account for 15% of Nephrolithiasis/Nephrocalcinosis. J Am Soc Nephrol 26(3):543–551. doi:10.1681/ASN.2014040388 PubMedCrossRefGoogle Scholar
  20. 20.
    Tiselius HG (2010) New horizons in the management of patients with cystinuria. Curr Opin Urol 20:169–173PubMedCrossRefGoogle Scholar
  21. 21.
    Thomas JC, DeMarco RT, Donohoe JM, Adams MC, Brock JW, Pope JC (2005) Pediatric ureteroscopic stone management. J Urol 174:1072–1074PubMedCrossRefGoogle Scholar
  22. 22.
    Finocchiaro R, D’Eufemia P, Celli M, Zaccagnini M, Viozzi L, Troiani P, Mannarino O, Giardini O (1998) Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure. Urol Res 26:401–405PubMedCrossRefGoogle Scholar
  23. 23.
    Sumorok N, Goldfarb DS (2013) Update on cystinuria. Curr Opin Nephrol Hypertens 22:427–431PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Nakagawa Y, Coe FL (1999) A modified cyanide-nitroprusside method for quantifying urinary cystine concentration that corrects for creatinine interference. Clin Chim Acta 289:57–68PubMedCrossRefGoogle Scholar
  25. 25.
    Goldfarb DS, Coe FL, Asplin JR (2006) Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int 69:1041–1047PubMedCrossRefGoogle Scholar
  26. 26.
    Patel SR, Wagner LE, Lubner MG, Nakada SY (2014) Radiopacity and hounsfield attenuation of cystine urolithiasis: case series and review of the literature. J Endourol 28:472–475PubMedCrossRefGoogle Scholar
  27. 27.
    Torricelli FC, Marchini GS, De S, Yamaçake KG, Mazzucchi E, Monga M (2014) Predicting urinary stone composition based on single-energy noncontrast computed tomography: the challenge of cystine. Urology 83:1258–1263PubMedCrossRefGoogle Scholar
  28. 28.
    Motley G, Dalrymple N, Keesling C, Fischer J, Harmon W (2001) Hounsfield unit density in the determination of urinary stone composition. Urology 58:170–173PubMedCrossRefGoogle Scholar
  29. 29.
    Mattoo A, Goldfarb DS (2008) Cystinuria. Semin Nephrol 28:181–191PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrandino MN, Pierre SA, Simmons WN, Paulson EK, Albala DM, Preminger GM (2010) Dual-energy computed tomography with advanced postimage acquisition data processing: improved determination of urinary stone composition. J Endourol 24:347–354PubMedCrossRefGoogle Scholar
  31. 31.
    Chevreau G, Troccaz J, Conort P, Renard-Penna R, Mallet A, Daudon M, Mozer P (2009) Estimation of urinary stone composition by automated processing of CT images. Urol Res 37:241–245PubMedCrossRefGoogle Scholar
  32. 32.
    Bhatta KM, Prien EL, Dretler SP (1989) Cystine calculi–rough and smooth: a new clinical distinction. J Urol 142:937–940PubMedGoogle Scholar
  33. 33.
    Kim SC, Hatt EK, Lingeman JE, Nadler RB, McAteer JA, Williams JC (2005) Cystine: helical computerized tomography characterization of rough and smooth calculi in vitro. J Urol 174:1468–1470PubMedCrossRefGoogle Scholar
  34. 34.
    Kim SC, Burns EK, Lingeman JE, Paterson RF, McAteer JA, Williams JC (2007) Cystine calculi: correlation of CT-visible structure, CT number, and stone morphology with fragmentation by shock wave lithotripsy. Urol Res 35:319–324PubMedCrossRefGoogle Scholar
  35. 35.
    Ng CS, Streem SB (1999) Contemporary management of cystinuria. J Endourol 13:647–651PubMedCrossRefGoogle Scholar
  36. 36.
    Biyani C, Cartledge JJ (2006) Cystinuria—diagnosis and management. EAU-EBU Updates Series 4:175–183CrossRefGoogle Scholar
  37. 37.
    Elkoushy MA, Violette PD, Andonian S (2012) Percutaneous instillation of chemolytytic, chemotherapeutic, and antifungal agents. In: Smith AD, Badlani GH, Preminger GM, Kavoussi LR (eds) Smith’s Textbbok of Endourology, 3rd edn. Blackwell Publishing LtdGoogle Scholar
  38. 38.
    Hesse A, Tiselius HG, Siener R, Hoppe B (2009) Cystine stones. In: (eds) Urinary Stones. Diagnosis, treatment, and prevention of recurrence., 3rd edn. S. Karger AG, BaselGoogle Scholar
  39. 39.
    Ahlstrand C, Tiselius HG (1993) Treatment of cystine urolithiasis by a combination of extracorporeal shock wave lithotripsy and chemolysis. J Stone Dis 5:32–38PubMedGoogle Scholar
  40. 40.
    Kachel TA, Vijan SR, Dretler SP (1991) Endourological experience with cystine calculi and a treatment algorithm. J Urol 145:25–28PubMedGoogle Scholar
  41. 41.
    Azili MN, Ozcan F, Tiryaki T (2014) Retrograde intrarenal surgery for the treatment of renal stones in children: factors influencing stone clearance and complications. J Pediatr Surg 49:1161–1165PubMedCrossRefGoogle Scholar
  42. 42.
    Kronenberg P, Traxer O (2014) In vitro fragmentation efficiency of holmium: yttrium-aluminum-garnet (YAG) laser lithotripsy—a comprehensive study encompassing different frequencies, pulse energies, total power levels and laser fibre diameters. BJU Int 114:261–267PubMedCrossRefGoogle Scholar
  43. 43.
    Ruggera L, Zanin M, Beltrami P, Zattoni F (2011) Retrograde transureteral approach: a safe and efficient treatment for recurrent cystine renal stones. Urol Res 39:411–415PubMedCrossRefGoogle Scholar
  44. 44.
    Cohen J, Cohen S, Grasso M (2013) Ureteropyeloscopic treatment of large, complex intrarenal and proximal ureteral calculi. BJU Int 111:E127–E131PubMedCrossRefGoogle Scholar
  45. 45.
    Al-Qahtani SM, Letendre J, Thomas A, Natalin R, Saussez T, Traxer O (2014) Which ureteral access sheath is compatible with your flexible ureteroscope. J Endourol 28:286–290PubMedCrossRefGoogle Scholar
  46. 46.
    Traxer O, Thomas A (2013) Prospective evaluation and classification of ureteral wall injuries resulting from insertion of a ureteral access sheath during retrograde intrarenal surgery. J Urol 189:580–584PubMedCrossRefGoogle Scholar
  47. 47.
    Jung HU, Frimodt-Møller PC, Osther PJ, Mortensen J (2006) Pharmacological effect on pyeloureteric dynamics with a clinical perspective: a review of the literature. Urol Res 34:341–350PubMedCrossRefGoogle Scholar
  48. 48.
    Preminger GM, Assimos DG, Lingeman JE, Nakada SY, Pearle MS, Wolf JS, AUA NGP (2005) Chapter 1: AUA guideline on management of staghorn calculi: diagnosis and treatment recommendations. J Urol 173:1991–2000PubMedCrossRefGoogle Scholar
  49. 49.
    Scoffone CM, Cracco CM, Cossu M, Grande S, Poggio M, Scarpa RM (2008) Endoscopic combined intrarenal surgery in Galdakao-modified supine Valdivia position: a new standard for percutaneous nephrolithotomy. Eur Urol 54:1393–1403PubMedCrossRefGoogle Scholar
  50. 50.
    Ganpule AP, Bhattu AS, Desai M (2015) PCNL in the twenty-first century: role of microperc, miniperc, and ultraminiperc. World J Urol 33:235–240PubMedCrossRefGoogle Scholar
  51. 51.
    Coe FL, Evan AP, Worcester EM, Lingeman JE (2010) Three pathways for human kidney stone formation. Urol Res 38:147–160PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Evan AP, Coe FL, Lingeman JE, Shao Y, Matlaga BR, Kim SC, Bledsoe SB, Sommer AJ, Grynpas M, Phillips CL, Worcester EM (2006) Renal crystal deposits and histopathology in patients with cystine stones. Kidney Int 69:2227–2235PubMedCrossRefGoogle Scholar
  53. 53.
    Assimos DG, Leslie SW, Ng C, Streem SB, Hart LJ (2002) The impact of cystinuria on renal function. J Urol 168:27–30PubMedCrossRefGoogle Scholar
  54. 54.
    Dent CE, Senior B (1955) Studies on the treatment of cystinuria. Br J Urol 27:317–332PubMedCrossRefGoogle Scholar
  55. 55.
    Dent CE, Friedman M, Green H, Watson LC (1965) Treatment of cystinuria. Br Med J 1:403–408PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Barbey F, Joly D, Rieu P, Méjean A, Daudon M, Jungers P (2000) Medical treatment of cystinuria: critical reappraisal of long-term results. J Urol 163:1419–1423PubMedCrossRefGoogle Scholar
  57. 57.
    Joly D, Rieu P, Méjean A, Gagnadoux MF, Daudon M, Jungers P (1999) Treatment of cystinuria. Pediatr Nephrol 13:945–950PubMedCrossRefGoogle Scholar
  58. 58.
    Bihl G, Meyers A (2001) Recurrent renal stone disease-advances in pathogenesis and clinical management. Lancet 358:651–656PubMedCrossRefGoogle Scholar
  59. 59.
    Al-Hermi B, Abbas B (2003) Cystinuria in arab countries. Saudi J Kidney Dis Transpl 14:358–366PubMedGoogle Scholar
  60. 60.
    Grases F, Costa-Bauza A, Prieto RM (2006) Renal lithiasis and nutrition. Nutr J 5:23PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Porena M, Guiggi P, Micheli C (2007) Prevention of stone disease. Urol Int 79(Suppl 1):37–46PubMedCrossRefGoogle Scholar
  62. 62.
    Rogers A, Kalakish S, Desai RA, Assimos DG (2007) Management of cystinuria. Urol Clin North Am 34:347–362PubMedCrossRefGoogle Scholar
  63. 63.
    Johri N, Cooper B, Robertson W, Choong S, Rickards D, Unwin R (2010) An update and practical guide to renal stone management. Nephron Clin Pract 116:c159–c171PubMedCrossRefGoogle Scholar
  64. 64.
    Fattah H, Hambaroush Y, Goldfarb DS (2014) Cystine nephrolithiasis. Transl Androl Urol 3:228–233PubMedCentralPubMedGoogle Scholar
  65. 65.
    Goodyer P (2004) The molecular basis of cystinuria. Nephron Exp Nephrol 98:e45–e49PubMedCrossRefGoogle Scholar
  66. 66.
    Copelovitch L (2012) Urolithiasis in children: medical approach. Pediatr Clin North Am 59:881–896PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Tiselius HG (2004) Recurrence prevention in patients with urinary tract stone disease. Sci World J 4:35–41CrossRefGoogle Scholar
  68. 68.
    Xu H, Zisman AL, Coe FL, Worcester EM (2013) Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother 14:435–447PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Sakhaee K (1994) Cystinuria: pathogenesis and treatment. Miner Electrolyte Metab 20:414–423PubMedGoogle Scholar
  70. 70.
    Sakhaee K (1996) Pathogenesis and medical management of cystinuria. Semin Nephrol 16:435–447PubMedGoogle Scholar
  71. 71.
    Chow GK, Streem SB (1996) Medical treatment of cystinuria: results of contemporary clinical practice. J Urol 156:1576–1578PubMedCrossRefGoogle Scholar
  72. 72.
    Rutchik SD, Resnick MI (1997) Cystine calculi. Diagnosis and management. Urol Clin North Am 24:163–171PubMedCrossRefGoogle Scholar
  73. 73.
    Rodman JS, Blackburn P, Williams JJ, Brown A, Pospischil MA, Peterson CM (1984) The effect of dietary protein on cystine excretion in patients with cystinuria. Clin Nephrol 22:273–278PubMedGoogle Scholar
  74. 74.
    Heilberg IP, Goldfarb DS (2013) Optimum nutrition for kidney stone disease. Adv Chronic Kidney Dis 20:165–174PubMedCrossRefGoogle Scholar
  75. 75.
    Jaeger P, Portmann L, Saunders A, Rosenberg LE, Thier SO (1986) Anticystinuric effects of glutamine and of dietary sodium restriction. N Engl J Med 315:1120–1123PubMedCrossRefGoogle Scholar
  76. 76.
    Lindell A, Denneberg T, Edholm E, Jeppsson JO (1995) The effect of sodium intake on cystinuria with and without tiopronin treatment. Nephron 71:407–415PubMedCrossRefGoogle Scholar
  77. 77.
    Pearle MS, Goldfarb DS, Assimos DG, Curhan G, Denu-Ciocca CJ, Matlaga BR, Monga M, Penniston KL, Preminger GM, Turk TM, White JR (2014) Medical management of kidney stones: AUA guideline. J Urol 192:316–324PubMedCrossRefGoogle Scholar
  78. 78.
    Fjellstedt E, Denneberg T, Jeppsson JO, Tiselius HG (2001) A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria. Urol Res 29:295–302PubMedCrossRefGoogle Scholar
  79. 79.
    Sterrett SP, Penniston KL, Wolf JS, Nakada SY (2008) Acetazolamide is an effective adjunct for urinary alkalization in patients with uric acid and cystine stone formation recalcitrant to potassium citrate. Urology 72:278–281PubMedCrossRefGoogle Scholar
  80. 80.
    Crawhall JC, Scowen EF, Watts RW (1963) Effect of penicillamine on cystinuria. Br Med J 1:588–590PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Dahlberg PJ, van DB, Kurtz SB, Wilson DM, Smith LH (1977) Clinical features and management of cystinuria. Mayo Clin Proc 52:533–542PubMedGoogle Scholar
  82. 82.
    Pak CY, Fuller C, Sakhaee K, Zerwekh JE, Adams BV (1986) Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol 136:1003–1008PubMedGoogle Scholar
  83. 83.
    Lindell A, Denneberg T, Hellgren E, Jeppsson JO, Tiselius HG (1995) Clinical course and cystine stone formation during tiopronin treatment. Urol Res 23:111–117PubMedCrossRefGoogle Scholar
  84. 84.
    Asplin DM, Asplin JR (2013) The Interaction of thiol drugs and urine pH in the treatment of cystinuria. J Urol 189:2147–2151PubMedCrossRefGoogle Scholar
  85. 85.
    Sloand JA, Izzo JL (1987) Captopril reduces urinary cystine excretion in cystinuria. Arch Intern Med 147:1409–1412PubMedCrossRefGoogle Scholar
  86. 86.
    Perazella MA, Buller GK (1993) Successful treatment of cystinuria with captopril. Am J Kidney Dis 21:504–507PubMedCrossRefGoogle Scholar
  87. 87.
    Cohen TD, Streem SB, Hall P (1995) Clinical effect of captopril on the formation and growth of cystine calculi. J Urol 154:164–166PubMedCrossRefGoogle Scholar
  88. 88.
    Dahlberg PJ, Jones JD (1989) Cystinuria: failure of captopril to reduce cystine excretion. Arch Intern Med 149(713):717Google Scholar
  89. 89.
    Coulthard M, Richardson J, Fleetwood A (1991) Captopril is not clinically useful in reducing the cystine load in cystinuria or cystinosis. Pediatr Nephrol 5:98PubMedCrossRefGoogle Scholar
  90. 90.
    Michelakakis H, Delis D, Anastasiadou V, Bartsocas C (1993) Ineffectiveness of captopril in reducing cystine excretion in cystinuric children. J Inherit Metab Dis 16:1042–1043PubMedCrossRefGoogle Scholar
  91. 91.
    Nakagawa Y, Asplin JR, Goldfarb DS, Parks JH, Coe FL (2000) Clinical use of cystine supersaturation measurements. J Urol 164:1481–1485PubMedCrossRefGoogle Scholar
  92. 92.
    Coe FL, Clark C, Parks JH, Asplin JR (2001) Solid phase assay of urine cystine supersaturation in the presence of cystine binding drugs. J Urol 166:688–693PubMedCrossRefGoogle Scholar
  93. 93.
    Dolin DJ, Asplin JR, Flagel L, Grasso M, Goldfarb DS (2005) Effect of cystine-binding thiol drugs on urinary cystine capacity in patients with cystinuria. J Endourol 19:429–432PubMedCrossRefGoogle Scholar
  94. 94.
    Pietrow P, Auge BK, Weizer AZ, Delvecchio FC, Silverstein AD, Mathias B, Albala DM, Preminger GM (2003) Durability of the medical management of cystinuria. J Urol 169:68–70PubMedCrossRefGoogle Scholar
  95. 95.
    Haritopoulos K, Fojtik P, Cross W, Cartledge J (2010) Impact of a metabolic stone clinic on management of patients with cystinuria: 5 years follow-up. Clin Ter 161:341–344PubMedGoogle Scholar
  96. 96.
    Kluner C, Hein PA, Gralla O, Hein E, Hamm B, Romano V, Rogalla P (2006) Does ultra-low-dose CT with a radiation dose equivalent to that of KUB suffice to detect renal and ureteral calculi. J Comput Assist Tomogr 30:44–50PubMedCrossRefGoogle Scholar
  97. 97.
    Kulkarni NM, Uppot RN, Eisner BH, Sahani DV (2012) Radiation dose reduction at multidetector CT with adaptive statistical iterative reconstruction for evaluation of urolithiasis: how low can we go. Radiology 265:158–166PubMedCrossRefGoogle Scholar
  98. 98.
    Pareek G, Steele TH, Nakada SY (2005) Urological intervention in patients with cystinuria is decreased with medical compliance. J Urol 174:2250–2252 discussion 2252 PubMedCrossRefGoogle Scholar
  99. 99.
    Lindell A, Denneberg T, Granerus G (1997) Studies on renal function in patients with cystinuria. Nephron 77:76–85PubMedCrossRefGoogle Scholar
  100. 100.
    Coe FL, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115:2598–2608PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Rimer JD, An Z, Zhu Z, Lee MH, Goldfarb DS, Wesson JA, Ward MD (2010) Crystal growth inhibitors for the prevention of l-cystine kidney stones through molecular design. Science 330:337–341PubMedCrossRefGoogle Scholar
  102. 102.
    Masotti A, Laurenzi C, Boenzi S, Pastore A, Taranta A, Bellomo F, Muraca M, Dionisi-Vici C, Bertucci P, Dello Strologo L, Emma F (2014) Gender-related effects on urine l-cystine metastability. Amino Acids 46:415–427PubMedCrossRefGoogle Scholar
  103. 103.
    Belldina EB, Huang MY, Schneider JA, Brundage RC, Tracy TS (2003) Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients. Br J Clin Pharmacol 56:520–525PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Wendt-Nordahl G, Sagi S, Bolenz C, Alken P, Michel MS, Knoll T (2008) Evaluation of cystine transport in cultured human kidney cells and establishment of cystinuria type I phenotype by antisense technology. Urol Res 36:25–29PubMedCrossRefGoogle Scholar
  105. 105.
    Kartha G, Calle JC, Marchini GS, Monga M (2013) Impact of stone disease: chronic kidney disease and quality of life. Urol Clin North Am 40:135–147PubMedCrossRefGoogle Scholar
  106. 106.
    Penniston KL, Nakada SY (2013) Development of an instrument to assess the health related quality of life of kidney stone formers. J Urol 189:921–930PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kim Hovgaard Andreassen
    • 1
  • Katja Venborg Pedersen
    • 2
  • Susanne Sloth Osther
    • 1
  • Helene Ulrik Jung
    • 1
  • Søren Kissow Lildal
    • 1
  • Palle Joern Sloth Osther
    • 1
  1. 1.Department of Urology, Urological Research CentreLillebaelt Hospital, University of Southern DenmarkFredericiaDenmark
  2. 2.Department of Clinical GeneticsLillebaelt Hospital, University of Southern DenmarkVejleDenmark

Personalised recommendations