Medscape is available in 5 Language Editions – Choose your Edition here.



  • Author: Chandra Shekhar Biyani, MS, MBBS, DUrol, FRCS(Urol), FEBU; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
Updated: Apr 16, 2015


Cystinuria is an autosomal-recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from the luminal fluid of the renal proximal tubule and small intestine. The only phenotypic manifestation of cystinuria is cystine urolithiasis, which often recurs throughout an affected individual’s lifetime. Surgical intervention is necessary, but the cornerstones of treatment are dietary and medical prevention of recurrent stone formation.

In 1810, Wollaston first described a different type of urinary calculi from the urinary bladder and coined the term cystic oxide.[1] Berzelius recognized that the compound was not an oxide, and he named it cystine because the material originated from the bladder.[2] In 1908, Sir Archibald Garrod identified cystinuria as one of the original "inborn errors of metabolism."[3] Yeh et al[4] and Dent and Rose[5] showed abnormal excretion of the dibasic amino acids lysine, arginine, and ornithine in persons with cystinuria. In 1955, Harris et al reported the complex autosomal-recessive pattern of inheritance of cystinuria.[6] In 1961, Milne et al demonstrated reduced intestinal absorption of dibasic amino acids in persons with cystinuria.[7]

In 1954, while studying skin sensitivity to penicillin and its derivatives, Tabachnick et al noted that one of the degradation products of penicillin, penicillamine, reacted with cystine to form a mixed disulfide, penicillamine cysteine.[8] In 1963, Crawhall et al first used penicillamine to treat patients with cystinuria.[9]

In recent years, understanding of the genetic and molecular components of cystinuria has advanced. In 1993, Lee et al cloned a human cDNA (rBAT [renal basic amino acid transporter]) in chromosome 2, encoding a transport protein for cystine and dibasic amino acids.[10] In 1997, Bisceglia et al identified type III cystinuria on band 19q13.1.[11]



Renal transport of cystine

Amino acids are readily filtered by the glomerulus and undergo nearly complete reabsorption by proximal tubular cells. Only 0.4% of the filtered cystine appears in the urine. Various authors have studied amino acid transport in cell membranes obtained from the proximal renal tubule of humans, rats, and rabbits. At least 2 transport systems are responsible for cystine reabsorption, as follows:

  • High-affinity system: This system is affected in persons with cystinuria. The high-affinity system mediates uptake of 10% of L-cystine and the dibasic amino acids at the apical membrane of the straight third segment (S3) of the proximal tubule.
  • Low-affinity system: This system is present in the S1-S2 part of the proximal tubule and is responsible for 90% of L-cystine reabsorption. The low-affinity process augments the high-affinity process. After absorption, each molecule of cystine is intracellularly converted to 2 molecules of cysteine. Cysteine exits at the basolateral membrane.

Genetic studies of DNA from families with cystinuria reveal a defective gene located on chromosome 2. The gene that codes for the cystine transporter, initially termed rBAT, is now known as SLC3A1 (SLC for solute carrier) in the international Genome Database. A second cystinuria gene on chromosome 19 is called SLC7A9. The normal SLC7A9 gene encodes a subunit of the cystine transporter called b 0,+ AT (amino acid transporter). The process of cystine uptake is activated by the SLC3A1 and SLC7A9 gene products. Transport of L-cystine in the brush-border membrane vesicle is sodium-independent and electrogenic. In persons with cystinuria, the movement of cystine or cysteine from the tubular cells into the blood is not affected.[12]

Intestinal transport of cystine

The high-affinity transporter is present in the apical brush-border membrane of the jejunum and is responsible for absorption of cystine and dibasic amino acids. Most patients with cystinuria have impaired absorption of cystine; however, cystine deficiency is not clinically significant because absorption of short-chain amino acids is not affected.

Normally, cystine and the other dibasic amino acids (ie, ornithine, lysine, arginine) are filtered at the glomerulus and reabsorbed in the proximal convoluted tubule by a high-affinity luminal transmembrane channel. Defects in this channel cause elevated levels of dibasic amino acid secretion in the urine. Whereas ornithine, lysine, and arginine are completely soluble, cystine is relatively insoluble at physiologic urine pH levels of 5-7, with a pKa level of 8.3. At a urine pH level of 7.8 and 8, the respective solubility of cystine is nearly doubled and tripled.

Dent and Senior demonstrated that the solubility of cystine is pH-dependent.[13] The solubility of cystine in urine is approximately 250 mg/L (1 mmol/L) up to a pH level of 7, but solubility increases with a higher pH level by up to 500 mg/L (2 mmol/L) or more above a pH level of 7.5, as depicted in the image below. Measurements in urine have clearly shown that cystine solubility increases linearly with increased ionic strength. Pak and colleagues showed that approximately 70 mg of additional cystine can be dissolved in each liter of solution, with an increase in ionic strength from 0.005-0.3.[14] In addition, at the same ionic strength and pH, cystine solubility varies depending on the particular type of electrolyte present. See the image below.

Cystine solubility in urine. Cystine solubility in urine.

In vitro experiments by Pak and Fuller in 1983 revealed that the highest solubility is accomplished in the presence of calcium chloride, followed by magnesium and sodium chloride.[15] Furthermore, cystine solubility is also affected by urinary macromolecules. The presence of colloid in normal urine has been shown to increase cystine solubility; however, the mechanism of this action is not clear. Because nothing inhibits cystine crystallization, the main determinant is urinary supersaturation. Heterogeneous nucleation of calcium oxalate, brushite, or hydroxyapatite does not occur in individuals with cystinuria.

Risk factors for cystine crystallization include (1) low pH level, (2) reduced ion strength, (3) the presence of cystine crystals, and (4) low levels of urinary macromolecules.

Cystine is a disulfide-linked homodimer of cysteine and has the following structure:


COOH-CHNH2-CH2 –SH Cysteine

Cystine is absorbed in the small intestine in a manner similar to that of the kidneys. In persons with cystinuria, intestinal absorption of cystine is also impaired to varying degrees. Metabolism of methionine is another source of serum cystine. Two type II membrane glycoproteins domains have been implicated in amino acid transport via the plasma membrane. The first is rBAT, and the second is 4F2HC (the heavy chain of the 4F2 antigen)

Two thirds of persons with cystinuria who form stones make pure cystine calculi, and one third have a mixture of cystine and calcium oxalate calculi. In 2002, Martins et al reported that calcium oxalate precipitation occurs by a salting-out process, ie, the reduction in solubility of a substance due to the addition of another substance to the system, rather than by the process of heterogenous nucleation.[16] Hypocitraturia, hypercalciuria, and hyperuricosuria are also frequently associated with cystinuria. Given their relatively uniform crystalline structure without lamellated cleavage planes, pure cystine calculi are among the hardest on Dretler's stone fragility index.

Cystinuria is an autosomal-recessive disease divided into 3 subtypes: Rosenberg I, II, and III. Cystinuria type I is the most common variant and has been mapped to band 2p16.3. Type I heterozygotes show normal aminoaciduria. Classic cystinuria, types II and III, were thought to be allelic variants, but recent linkage analyses reveal type III to be a defect of an uncharacterized gene (SLC7A9) on band 19q13.1. Heterozygotes of types II and III often manifest cystinuria without cystine calculi and may be at increased risk for other types of urolithiasis. Type I heterozygotes are distinguished by normal levels of urinary cystine.

Unlike type I and type II homozygotes, type III homozygotes show an increase in plasma cystine concentration after oral cystine administration. Harris et al reported the complex nature of the genetics of cystinuria by measuring the level of urinary cystine excretion in the parents (obligate heterozygotes) of cystinuria probands and found fully recessive alleles (both parents excreted cystine in the reference range) and dominant alleles (both parents excreted cystine at high levels).[6]

To classify cystinuria clinically, urinary cystine can be measured in each parent of a proband as phenotype I (recessive, urinary cystine level < 100 µmol/g of creatinine), phenotype II (dominant, urinary cystine level >1000 µmol/g of creatinine), and phenotype III (partially dominant, urinary cystine level 100-1000 µmol/g of creatinine). Cystinuria can also be classified based on the age at which symptoms first appear (ie, infantile, juvenile, adolescent).

In healthy individuals, the upper limit for cystine excretion is 20 mg/g of creatinine (< 10 µmol/mmol of creatinine). Homozygotes excrete more than 400 mg/d (1.7 mmol/d), and cystine excretion in homozygous patients is usually 600-1400 mg/d (2.5-5.8 mmol/d). Heterozygotes with type I and III cystinuria excrete less than 200 mg/d (0.8 mmol/d) and do not form stones. Type II heterozygotes excrete up to 200-400 mg/d, but these patients may form stones. The incidence of stone formation increases when urinary cystine concentration exceeds 700 µmol/L (170 mg/L).


In recent years, with the advancements in molecular biology, new insights have accumulated regarding the pathophysiology of cystinuria. In 1992, several investigators reported the expression cloning of a 2.3-kilobase renal cDNA (D2H or rBAT) that induced sodium-independent uptake of cystine and the dibasic amino acids in cRNA-injected Xenopus laevis oocytes. The rBAT gene was mapped to chromosome 2 (band 2p21) between D2S119 and D2S288. This gene is now named SLC3A1 in the Genome Database.

Immunohistochemical and in situ hybridization studies revealed that rBAT is expressed in cells of the S3 (pars recta) segment of the proximal tubule and small intestine at the luminal brush-border membrane. In 1995, Gasparini et al reported that mutations in SLC3A1 occurred in patients with type I cystinuria and not in patients with type II or III cystinuria.[17] To date, more than 60 different mutations have been described, including both small and large deletions of DNA base pairs from the gene. One of the most common genetic alterations in SLC3A1 is called M467T, and most mutations tend to be population-specific. The M467T mutation is fairly common in Mediterranean populations. Interestingly, it accounted for 40% of mutations in a Spanish cohort of families and was rare in patients studied in Quebec, Canada.

In 1999, the SLC7A9 (BAT1) gene was isolated. The gene encodes a 487–amino acid protein and was mapped to chromosome 19 (band 19q13) between D19S414 and D19S220. The BAT1 product appears to be a membrane protein with 12 membrane-spanning regions. Mutations in the BAT1 gene probably cause non–type I cystinuria (Rosenberg type II and III). Mutations at the 19q locus are especially common among Libyan Jews, and the risk of urolithiasis in patients who inherit 2 such 19q locus mutations is roughly comparable to that in patients who inherit 2 rBAT mutations.

A number of mutations in this gene have been reported. The most common mutation in Libyan Jews resulted in a methionine replacing the valine amino acid residue (V170M) in the protein. In heterozygotes with the V170M mutation, urinary cystine concentrations range from 86-1238 µmol/g of creatinine. Thus, some of the values in V170M heterozygotes are consistent with type III cystinuria and others with type II cystinuria.

An apparent distinguishing feature between type II and type III cystinuria is the lack of intestinal cystine absorption in type II homozygotes. In 2000, Pras suggested a new classification based on molecular analysis.[18] Recently, Dello Strologo et al have proposed a new genetic classification, as follows:[19]

  • Type A, mutation of both alleles of SLC3A1: Heterozygotes show a normal amino acid urinary pattern.
  • Type B, mutation of both alleles of SLC7A9: Heterozygotes usually show an increase of cystine and dibasic amino acid urinary excretion.
  • Type AB, cystinuria caused by 1 mutation in SLC3A1 and 1 mutation in SLC7A9: Mixed-type cystinuria may be caused by the interaction of 2 distinct mutant genes, and the protein encoded by the 19q gene directly interacts with rBAT in the S3 segment of the proximal tubule (see the Table).

Martens et al (2008) recently reported 3 gene-deletion syndromes associated with type A cystinuria: 2p21 deletion syndrome, hypotonia-cystinuria syndrome (HCS), and an atypical form of hypotonia-cystinuria syndrome. Both alleles of SLC3A1 and PREPL are missing in patients with HCS. An additional gene (C2orf34) is deleted in atypical HCS.[20]

Table. Classification of Cystinuria (Open Table in a new window)

Rosenberg et al [21] Type I Type II Type III
Molecular Type I Non–Type I
Responsible gene SLC3A1 SLC7A9
Band 2p21 19q13.1
No. of mutations >60 39
Most common mutation M467 V170M
Population affected Mediterranean Spanish persons, 40% Libyan Jews
Deletion rate 54% 25%
Protein rBAT BAT1
Amino acid transport system
Localization in proximal converted tubule S3 S1, S2
Transporter characteristic High affinity, low capacity Low affinity, high capacity
Clinical features
Homozygotes Symptomatic approximately 90% symptomatic
Heterozygotes Asymptomatic approximately 10%-13% symptomatic
Urinary cystine levels Normal Elevated +++++ Elevated +
Plasma cystine levels after an oral load test Same Same or slight rise Increased
Intestinal transport Absent (no transport of cystine, lysine, or arginine) Absent Reduced

Recent evidence suggests that the 4F2HC/4F2LC complex accounts for the Y+L amino acid transport system at the basolateral surface of intestinal and renal proximal tubular cells and that the mutations of the 4F2LC gene (SLC7A7) on band 14q11-13 cause the rare recessive disease called lysine-protein intolerance.


See the list below:

  • rBAT, a 90-kd type II glycoprotein, is a high-affinity, sodium-independent transporter for dibasic amino acids in the proximal convoluted renal tubules in rodents.
  • The human rBAT gene has been localized on band 2p21. Interestingly, linkage analysis suggests that this is the same region to which a cystinuric locus, SLC3A1, has been identified.
  • More than 60 mutations at the rBAT/SLC3A1 locus have been identified in patients with cystinuria worldwide.
  • Type III and II cystinuria (non–type I) have been linked to band 19p13.1 ( SLC7A9); however, further studies are needed to determine the exact role of the SLC7A9 gene.
  • Approximately 50% of children with 2 SLC3A1 mutations (classic homozygous type I cystinuria) develop at least one stone within the first decade of life.



United States

Cystine accounts for 1% of adult and 6%-8% of pediatric urinary calculi. The prevalence of heterozygosity is approximately 1 case per 20-200 persons. Homozygous cystinuria affects 1 person per 15,000 population.


Worldwide, the overall prevalence is 1 person per 7000 population. Prevalences of cystinuria are 1 case in 18,000 in Japan, 1 case in 2500 in Israel, 1 case in 2000 in Great Britain, 1 case in 4000 in Australia, 1 case in 1900 in Spain, 1 case in 2500 in Libyan Jews, and 1 case in 100,000 in Sweden. The Quebec Genetic Network Neonatal Screening Program reported the incidence of persistent cystinuria as 562 cases per million infants, a rate 7 times higher than for clinically manifested cystinuria in the adult population of Quebec. This suggests that many cystinuric individuals do not form stones.


Barbey et al reported one new stone formation per patient per year and an average of one surgical procedure every 3 years, with 7 surgical procedures for nephrolithiasis by middle age.[22] Urinary calculi are generally the only manifestation of cystinuria, although 10% of cases are complicated by hypertension, and one study found a weak association with short stature. Patients with cystinuria who form stones are at higher risk for anatomical renal loss (nephrectomy) than those who form calcium oxalate stones. The risk of renal impairment is high; up to 70% of patients may be affected depending on the length of follow-up and medical therapy. However, according to Lindell et al, end-stage renal disease occurs in less than 5% of patients with cystinuria.[23] In 1998, Chow and Streem reported that the probability of a recurrence-free survival at 1-year and 5-year follow-up is 0.73 and 0.27, respectively.[24]


Cystinuria is more common in white persons. Up to 1 in 2500 Jews of Libyan extraction are affected.


Cystinuria has no age predilection, although men are more severely affected. An incidence of 0.42 stone episodes for in males with cystinuria and 0.21 in females with the disease per annum has been reported.[19]


Cystine stones are common in the second or third decade of life. The peak age of first renal calculus is 22 years, although up to 22% of these patients develop calculi in childhood.

Contributor Information and Disclosures

Chandra Shekhar Biyani, MS, MBBS, DUrol, FRCS(Urol), FEBU Consulting Urologist, Department of Urology, Pinderfields General Hospital, The Mid-Yorkshire Hospitals NHS Trust, UK

Chandra Shekhar Biyani, MS, MBBS, DUrol, FRCS(Urol), FEBU is a member of the following medical societies: British Medical Association, International College of Surgeons, British Association of Urological Surgeons, European Association of Urology

Disclosure: Nothing to disclose.


Jon Cartledge, MB, BCh, MD, FRCS Consulting Urologist, Pyrah Department of Urology, St James's University Hospital, Leeds, UK

Jon Cartledge, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

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, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Additional Contributors

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, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

  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. 1955 Aug. 20(1):57-91. [Medline].

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

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

  9. Crawhall JC, Scowen EF, Watts RW. Effect of penicillamine on cystinuria. Br Med J. 1963 Mar 2. 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. 1993 May. 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. 1997 Mar. 60(3):611-6. [Medline].

  12. Chillarón J, Font-Llitjós M, Fort J, Zorzano A, Goldfarb DS, Nunes V, et al. Pathophysiology and treatment of cystinuria. Nat Rev Nephrol. 2010 Jul. 6(7):424-34. [Medline].

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

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

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

  16. 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. 2002 Jan. 167(1):317-21. [Medline].

  17. 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. 1995 Oct. 57(4):781-8. [Medline].

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

  19. 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. 2002 Oct. 13(10):2547-53. [Medline].

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

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

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

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

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

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

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

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

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

  29. van Hoeve K, Vermeersch P, Regal L, Levtchenko E. Necessity of fractionated urine collection for monitoring patients with cystinuria. Clin Chem. 2011 May. 57(5):780-1. [Medline].

  30. 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].

  31. Tiselius HG. New horizons in the management of patients with cystinuria. Curr Opin Urol. 2010 Mar. 20(2):169-73. [Medline].

  32. Goldfarb DS. Potential pharmacologic treatments for cystinuria and for calcium stones associated with hyperuricosuria. Clin J Am Soc Nephrol. 2011 Aug. 6(8):2093-7. [Medline]. [Full Text].

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

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

  35. Rimer JD, An Z, Zhu Z, et al. Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design. Science. 2010 Oct 15. 330(6002):337-41. [Medline].

  36. Goldfarb DS. Potential pharmacologic treatments for cystinuria and for calcium stones associated with hyperuricosuria. Clin J Am Soc Nephrol. 2011 Aug. 6(8):2093-7. [Medline].

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

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

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

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

  41. 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. 1993 Jul 15. 268(20):14842-9. [Medline].

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

  43. 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. 1999 Mar. 21(3):297-301. [Medline].

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

  45. 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. 1995 Jun. 95(6):633-6. [Medline].

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

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

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

  49. 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. 1999 Sep. 23(1):52-7. [Medline].

  50. 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. 2001 Oct. 29(5):295-302. [Medline].

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  70. Segal S, Thier SO. Cystinuria. 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.

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

  72. 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. 1994 Nov 15. 24(2):413-4. [Medline].

Cystine solubility in urine.
Electron microscopic picture showing cystine crystals.
Plain radiograph of the abdomen showing cystine staghorn stones.
Faintly opaque (ground-glass appearance) left lower ureteric stone.
Intravenous urogram showing left ureterohydronephrosis.
Renal sonogram demonstrating renal calculi in the lower pole.
Treatment algorithm for cystinuria.
Table. Classification of Cystinuria
Rosenberg et al [21] Type I Type II Type III
Molecular Type I Non–Type I
Responsible gene SLC3A1 SLC7A9
Band 2p21 19q13.1
No. of mutations >60 39
Most common mutation M467 V170M
Population affected Mediterranean Spanish persons, 40% Libyan Jews
Deletion rate 54% 25%
Protein rBAT BAT1
Amino acid transport system
Localization in proximal converted tubule S3 S1, S2
Transporter characteristic High affinity, low capacity Low affinity, high capacity
Clinical features
Homozygotes Symptomatic approximately 90% symptomatic
Heterozygotes Asymptomatic approximately 10%-13% symptomatic
Urinary cystine levels Normal Elevated +++++ Elevated +
Plasma cystine levels after an oral load test Same Same or slight rise Increased
Intestinal transport Absent (no transport of cystine, lysine, or arginine) Absent Reduced
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.