eMedicine Specialties > Urology > Stones

Cystinuria: Follow-up

Author: Chandra Shekhar Biyani, MBBS, MS, DUrol, FRCS(Urol), FEBU, Consulting Urologist, Department of Urology, Pinderfields General Hospital, UK
Coauthor(s): Jon Cartledge, MD, FRCS (Urol), Consulting Urologist, Pyrah Department of Urology, St James's University Hospital, UK
Contributor Information and Disclosures

Updated: Jun 23, 2009

Follow-up

Further Outpatient Care

  • Regular follow-up
    • Follow-up care in patients with cystinuria is mandatory because of the relentless tendency of cystine stones to recur. Patients should have frequent clinical, radiological, and laboratory surveillance.
    • Patients should be taught to use Nitrazine paper to check their pH level and to try to titrate the medication and diet on their own.
  • Initial follow-up
    • Ensure that patients are following a diet low in protein and sodium chloride.
    • Determine urinary pH level, and check first-morning urine for cystine crystals.
    • Repeat 24-hour urinary cystine measurements until the cystinuric state is well controlled and stable.
    • Renal function should be regularly checked. RBC counts, WBC counts, and platelet counts should be monitored for patients on D-penicillamine and tiopronin.
    • Abdominal radiography and renal ultrasonography should be routine.
  • Surveillance
    • Maintain close follow-up for severe forms of cystinuria. Annually perform 24-hour urine testing and imaging for patients with stable disease.
    • A multidisciplinary approach to care, including involvement from nephrologists, renal dietitians, and nurses, should be initiated early in the disease, with close patient follow-up.

Deterrence/Prevention

  • Family screening helps identify patients with a genetic predisposition for cystinuria.
  • Hydration sufficient to maintain 3 L or more of urine output per day is a well-accepted stone-prevention measure.
  • Dietary restrictions must be instituted and followed.
  • Urinary alkalization (goal, urine pH level >7.5) is necessary.

Complications

  • Recurrence: One study reported 1.22 stone episodes per year.
  • Chronic pyelonephritis - 19%
  • Renal impairment - Approximately 70%
  • Risk for nephrectomy - 10-20%
  • End-stage renal failure - 5%
  • Hypertension - 10%
  • Mental illness and mental retardation

Prognosis

  • The probability of a recurrence-free survival at 1- and 5-year follow-up is 0.73 and 0.27, respectively.

Patient Education

  • Cystinuria is an inherited metabolic disorder; therefore, patient education is extremely important. The children of parents who both have cystinuria have a 100% chance of becoming cystinuric. If one parent is fully cystinuric and the other is a carrier, the chance of each child becoming fully cystinuric is 50%. If both parents are carriers, the chance of each child becoming cystinuric is 25%. If one parent is cystinuric and the other is neither cystinuric nor a carrier, the chance of each child becoming cystinuric is nil.
  • To help prevent recurrence, counsel and educate patients in whom recurrence was caused by medication noncompliance regarding the importance of proper diet and the necessity of medication compliance.
  • Further information about cystinuria is available on the following Web sites:
  • For excellent patient education resources, visit eMedicine's Kidneys and Urinary Systems Center. Also, see eMedicine's patient education article Kidney Stones.

Miscellaneous

Medicolegal Pitfalls

  • Regular medical treatment is mandatory in patients with cystinuria because of the relentless tendency of cystine stones to recur.
  • Patients must be cautioned that a urinary pH level of more than 7.8 causes a predisposition to calcium phosphate stone formation.
  • Because patients with cystinuria in whom stones are forming are at risk for renal loss, follow-up care with regular monitoring is mandatory.
  • Prescribing a treatment regimen that is considered the standard of care is mandatory.

Special Concerns

  • New insights into the genetic basis of cystinuria may provide new targets for improved pharmacotherapy or genetic therapy for this disease.
  • Further studies are necessary to elucidate the influence of other contributing factors such as hypocitraturia, hyperuricemia, hyperuricosuria, and hypercalciuria.
 


More on Cystinuria

Overview: Cystinuria
Differential Diagnoses & Workup: Cystinuria
Treatment & Medication: Cystinuria
Follow-up: Cystinuria
Multimedia: Cystinuria
References
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References

  1. Wollaston WH. On cystic oxide. A new species of urinary calculus. Trans R Soc London. 1810;100:223-30.

  2. Berzellius J. Calculus urinaires. Traite Chem. 1833;7:424.

  3. Garrod AE. Inborn errors of metabolism. Lancet. 1908;2:1, 73, 142, 214.

  4. Yeh HL, Frankl W, Dunn MS. The urinary excretion of amino acids by cystinuric subjects. Am J Med Sci. 1974;214:507-12.

  5. Dent CC, Rose GA. Amino acid metabolism in cystinuria. Q J Med New Series. 1974;214:507-12.

  6. Harris H, Mittwoch U, Robson EB, Warren FL. Phenotypes and genotypes in cystinuria. Ann Hum Genet. Aug 1955;20(1):57-91. [Medline].

  7. Milne MD, Asatoor AM, Edwards KD, Loughridge LW. The intestinal absorption defect in cystinuria. Gut. Dec 1961;2(4):323-37. [Medline].

  8. Tabachnick M, Eisen HN, Levine B. A new mixed disulphide: penicillamine-cysteine. Nature. Oct 9 1954;174(4432):701-2. [Medline].

  9. Crawhall JC, Scowen EF, Watts RW. Effect of penicillamine on cystinuria. Br Med J. Mar 2 1963;5330:588-90. [Medline].

  10. Lee WS, Wells RG, Sabbag RV, et al. Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. J Clin Invest. May 1993;91(5):1959-63. [Medline].

  11. Bisceglia L, Calonge MJ, Totaro A, et al. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1. Am J Hum Genet. Mar 1997;60(3):611-6. [Medline].

  12. Dent CE, Senior B. Studies on the treatment of cystinuria. Br J Urol. Dec 1955;27(4):317-32. [Medline].

  13. Pak CY, Fuller C, Sakhaee K, et al. Management of cystine nephrolithiasis with alpha- mercaptopropionylglycine. J Urol. Nov 1986;136(5):1003-8. [Medline].

  14. Pak CY, Fuller CJ. Assessment of cystine solubility in urine and of heterogeneous nucleation. J Urol. May 1983;129(5):1066-70. [Medline].

  15. Martins MC, Meyers AA, Whalley NA, Rodgers AL. Cystine: a promoter of the growth and aggregation of calcium oxalate crystals in normal undiluted human urine. J Urol. Jan 2002;167(1):317-21. [Medline].

  16. Gasparini P, Calonge MJ, Bisceglia L, et al. Molecular genetics of cystinuria: identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. Am J Hum Genet. Oct 1995;57(4):781-8. [Medline].

  17. Pras E. Cystinuria at the turn of the millennium: clinical aspects and new molecular developments. Mol Urol. Winter 2000;4(4):409-14. [Medline].

  18. Dello Strologo L, Pras E, Pontesilli C, et al. Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J Am Soc Nephrol. Oct 2002;13(10):2547-53. [Medline].

  19. Martens K, Jaeken J, Matthijs G, Creemers JW. Multi-system disorder syndromes associated with cystinuria type I. Curr Mol Med. Sep 2008;8(6):544-50. [Medline].

  20. Rosenberg LE, Downing S, Durant JL, Segal S. Cystinuria: biochemical evidence for three genetically distinct diseases. J Clin Invest. Mar 1966;45(3):365-71. [Medline].

  21. Barbey F, Joly D, Rieu P, et al. Medical treatment of cystinuria: critical reappraisal of long-term results. J Urol. May 2000;163(5):1419-23. [Medline].

  22. Lindell A, Denneberg T, Granerus G. Studies on renal function in patients with cystinuria. Nephron. 1997;77(1):76-85. [Medline].

  23. Chow GK, Streem SB. Contemporary urological intervention for cystinuric patients: immediate and long-term impact and implications. J Urol. Aug 1998;160(2):341-4; discussion 344-5. [Medline].

  24. Sakhaee K, Poindexter JR, Pak CY. The spectrum of metabolic abnormalities in patients with cystine nephrolithiasis. J Urol. Apr 1989;141(4):819-21. [Medline].

  25. Daudon M, Cohen-Solal F, Barbey F, et al. Cystine crystal volume determination: a useful tool in the management of cystinuric patients. Urol Res. Jul 2003;31(3):207-11. [Medline].

  26. Coe FL, Clark C, Parks JH, Asplin JR. Solid phase assay of urine cystine supersaturation in the presence of cystine binding drugs. J Urol. Aug 2001;166(2):688-93. [Medline].

  27. Dolin DJ, Asplin JR, Flagel L, et al. Effect of cystine-binding thiol drugs on urinary cystine capacity in patients with cystinuria. J Endourol. Apr 2005;19(3):429-32. [Medline].

  28. Pontoni G, Rotondo F, Spagnuolo G, et al. Diagnosis and follow-up of cystinuria: use of proton magnetic resonance spectroscopy. Amino Acids. 2000;19(2):469-76. [Medline].

  29. Sloand JA, Izzo JL Jr. Captopril reduces urinary cystine excretion in cystinuria. Arch Intern Med. Aug 1987;147(8):1409-12. [Medline].

  30. Koide T, Yamaguchi S, Utsonomiya M. A new therapeutic agent for cystinuria. In: VII International Symposium on Urolithiasis. Cairns, Australia. New York, NY: Plenum; 1992:168.

  31. Kachel TA, Vijan SR, Dretler SP. Endourological experience with cystine calculi and a treatment algorithm. J Urol. Jan 1991;145(1):25-8. [Medline].

  32. Miyagi K, Nakada F, Ohshiro S. Effect of glutamine on cystine excretion in a patient with cystinuria. N Engl J Med. Jul 26 1979;301(4):196-8. [Medline].

  33. Akakura K, Egoshi K, Ueda T, et al. The long-term outcome of cystinuria in Japan. Urol Int. 1998;61(2):86-9. [Medline].

  34. Assimos DG, Leslie SW, Ng C, et al. The impact of cystinuria on renal function. J Urol. Jul 2002;168(1):27-30. [Medline].

  35. Bertran J, Werner A, Chillaron J, et al. Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes. J Biol Chem. Jul 15 1993;268(20):14842-9. [Medline].

  36. Bhatta KM, Prien EL Jr, Dretler SP. Cystine calculi--rough and smooth: a new clinical distinction. J Urol. Oct 1989;142(4):937-40. [Medline].

  37. Borsani G, Bassi MT, Sperandeo MP, et al. SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. Mar 1999;21(3):297-301. [Medline].

  38. Botzenhart E, Vester U, Schmidt C, et al. Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int. Oct 2002;62(4):1136-42. [Medline].

  39. Calonge MJ, Nadal M, Calvano S, et al. Assignment of the gene responsible for cystinuria (rBAT) and of markers D2S119 and D2S177 to 2p16 by fluorescence in situ hybridization. Hum Genet. Jun 1995;95(6):633-6. [Medline].

  40. Chow GK, Streem SB. Medical treatment of cystinuria: results of contemporary clinical practice. J Urol. Nov 1996;156(5):1576-8. [Medline].

  41. Cohen TD, Streem SB, Hall P. Clinical effect of captopril on the formation and growth of cystine calculi. J Urol. Jul 1995;154(1):164-6. [Medline].

  42. Dretler SP, Pfister RC, Newhouse JH, Prien EL Jr. Percutaneous catheter dissolution of cystine calculi. J Urol. Feb 1984;131(2):216-9. [Medline].

  43. Feliubadalo L, Font M, Purroy J, et al. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. International Cystinuria Consortium. Nat Genet. Sep 1999;23(1):52-7. [Medline].

  44. Fjellstedt E, Denneberg T, Jeppsson JO, Tiselius HG. A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria. Urol Res. Oct 2001;29(5):295-302. [Medline].

  45. Gambaro G, Favaro S, D'Angelo A. Risk for renal failure in nephrolithiasis. Am J Kidney Dis. Feb 2001;37(2):233-43. [Medline].

  46. Goodyer P, Boutros M, Rozen R. The molecular basis of cystinuria: an update. Exp Nephrol. May-Jun 2000;8(3):123-7. [Medline].

  47. Goodyer P, Saadi I, Ong P, et al. Cystinuria subtype and the risk of nephrolithiasis. Kidney Int. Jul 1998;54(1):56-61. [Medline].

  48. Heimbach D, Jacobs D, Müller SC, Hesse A. Improving cystine stone therapy: an in vitro study of dissolution. Urology. Jan 2000;55(1):17-21. [Medline].

  49. Ito H, Egoshi K, Mizoguchi K, Akakura K. Advances in genetic aspects of cystinuria. Mol Urol. 2000;4(4):403-8. [Medline].

  50. Jaeger P, Portmann L, Saunders A, et al. Anticystinuric effects of glutamine and of dietary sodium restriction. N Engl J Med. Oct 30 1986;315(18):1120-3. [Medline].

  51. Kashiwazaki S, Shiokawa Y. Bucillamine: a new immunomodulator. Int M J Immunother. 1987;3:1-6.

  52. Knoll LD, Segura JW, Patterson DE, et al. Long-term followup in patients with cystine urinary calculi treated by percutaneous ultrasonic lithotripsy. J Urol. Aug 1988;140(2):246-8. [Medline].

  53. Martensson J, Denneberg T, Lindell A, Textorius O. Sulfur amino acid metabolism in cystinuria: a biochemical and clinical study of patients. Kidney Int. Jan 1990;37(1):143-9. [Medline].

  54. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. Mar 2008;28(2):181-91. [Medline].

  55. McDonald MW, Stoller ML. Cystinuria: advances in medical therapy. Contemp Urol. Apr 1996;8:20-36.

  56. Milliner DS. Cystinuria. Endocrinol Metab Clin North Am. Dec 1990;19(4):889-907. [Medline].

  57. Pareek G, Steele TH, Nakada SY. Urological intervention in patients with cystinuria is decreased with medical compliance. J Urol. Dec 2005;174(6):2250-2, discussion 2252. [Medline].

  58. Pietrow PK, Auge BK, Weizer AZ, et al. Durability of the medical management of cystinuria. J Urol. Jan 2003;169(1):68-70. [Medline].

  59. Rudnick DM, Bennett PM, Dretler SP. Retrograde renoscopic fragmentation of moderate-size (1.5-3.0-cm) renal cystine stones. J Endourol. Sep 1999;13(7):483-5. [Medline].

  60. Rutchik SD, Resnick MI. Cystine calculi. Diagnosis and management. Urol Clin North Am. Feb 1997;24(1):163-71. [Medline].

  61. Sakhaee K, Sutton RA. Pathogenesis and medical management of cystinuria. In: Coe FL, Favus MJ, Pak C, eds. Kidney stones: Medical and Surgical Managements. Philadelphia, Pa: Lippincott-Raven; 1996:1007-17.

  62. Saltzman N, Gittes RF. Chemolysis of cystine calculi. J Urol. Oct 1986;136(4):846-9. [Medline].

  63. Schmidt J, Madersbacher S, Hochreiter WW, et al. Simultaneous replacement of both ureters with small intestine in a woman with cystinuria. J Urol. Dec 2001;166(6):2315-6. [Medline].

  64. Segal S, Thier SO. Cystinuria. In: Scriver CR, Beaudet AL, Sly WS, Valle S, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995:3581-601.

  65. Streem SB, Hall P. Effect of captopril on urinary cystine excretion in homozygous cystinuria. J Urol. Dec 1989;142(6):1522-4. [Medline].

  66. Zhang XX, Rozen R, Hediger MA, et al. Assignment of the gene for cystinuria (SLC3A1) to human chromosome 2p21 by fluorescence in situ hybridization. Genomics. Nov 15 1994;24(2):413-4. [Medline].

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Further Reading

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Keywords

cystinuria, urolithiasis, cystine urolithiasis, urinary calculi, stone formation, amino acids, cystine, cysteine, SLC3A1, SLC7A9, rBAT, urinary alkalinization, hydration, D-penicillamine, tiopronin, Thiola, captopril, extracorporeal shockwave lithotripsy, ESWL, extracorporeal shock wave lithotripsy, retrograde endoscopic lithotripsy, percutaneous nephrolithotomy, PCNL, stone removal, urinary tract stone, kidney stone, recurrent stone formation, stone recurrence, urinary calculus, cystic oxide, cystine stones, cystine stone formers, ornithine, arginine, lysine

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Contributor Information and Disclosures

Author

Chandra Shekhar Biyani, MBBS, MS, DUrol, FRCS(Urol), FEBU, Consulting Urologist, Department of Urology, Pinderfields General Hospital, UK
Chandra Shekhar Biyani, MBBS, MS, DUrol, FRCS(Urol), FEBU is a member of the following medical societies: British Association of Urological Surgeons, British Medical Association, European Association of Urology, and International College of Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Jon Cartledge, MD, FRCS (Urol), Consulting Urologist, Pyrah Department of Urology, St James's University Hospital, UK
Jon Cartledge, MD, FRCS (Urol) is a member of the following medical societies: British Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Direct of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

 
 
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