Cystinuria: An Inherited Cause of Repeated Kidney Stones

Table of Contents

1. A Faulty Kidney Transporter
2. Two Genes and Three Types
3. How Common It Is
4. How Cystine Stones Form
5. When Stones Usually Begin
6. How It Is Diagnosed
7. Fluid and Urine Alkalinisation
8. Salt and Protein in the Diet
9. Thiol Drugs: Tiopronin and D-Penicillamine
10. The Captopril Evidence
11. Surgery to Remove Stones
12. Kidney Function and Recurrence
13. Newer Agents Under Study
14. What Is Not Known
15. Key Research Papers
16. Connections
17. Featured Videos

A Faulty Kidney Transporter

Every day the kidneys filter a large volume of fluid out of the blood. Most of the useful molecules in that fluid, including amino acids, are pulled back into the body by transporters in the first stretch of each kidney tubule, the proximal tubule. In cystinuria one of those transporters does not work. It normally carries cystine and three "dibasic" amino acids — lysine, arginine and ornithine — and the same transporter defect is found in the lining of the gut (Calonge 1994; Mattoo 2008).

Of the four amino acids that escape into the urine, only cystine causes trouble. Lysine, arginine and ornithine dissolve easily; cystine does not. A 2008 review states that "the only clinically significant manifestation is recurrent nephrolithiasis secondary to the poor solubility of cystine in urine" (Mattoo 2008). Cystine is two molecules of the amino acid cysteine joined by a sulfur-to-sulfur bond; the story of how it was first found in a bladder stone in 1810 is told on the Cysteine history page.

Cystinuria has a long place in medical history. In his 1908 Croonian Lectures, the physician Archibald Garrod used it as one of four examples of an "inborn error of metabolism", alongside albinism, alkaptonuria and pentosuria (Scriver 2008).

Two Genes and Three Types

The transporter is built from two protein parts, and each part is made by a different gene. SLC3A1, on chromosome 2, makes the heavy part (called rBAT); SLC7A9, on chromosome 19, makes the light part (Eggermann 2012). In 1994 a team reported six mutations in the rBAT gene in families with cystinuria; they accounted for 30% of the cystinuria chromosomes studied, and the commonest one nearly abolished the transporter's activity in frog egg cells (Calonge 1994).

An international consortium gathered genetic and clinical data on 224 people with cystinuria and proposed the classification used today (Dello Strologo 2002):

• Type A — two faulty copies of SLC3A1; 45.2% of the patients in that database.
• Type B — two faulty copies of SLC7A9; 53.2%.
• Type AB — one faulty copy of each gene; 1.6%, described by the authors as "a possible third type".

The same study looked at 189 carriers with one faulty gene. All SLC3A1 carriers and 14% of SLC7A9 carriers had normal urine amino acid levels; the remaining SLC7A9 carriers passed raised amounts (Dello Strologo 2002). This is why cystinuria is described as autosomal recessive for SLC3A1 but variable for SLC7A9, where clinical severity can differ even inside one family (Eggermann 2012). A 2020 US consensus statement describes the disorder as having "both autosomal recessive and incompletely dominant inheritance" (Eisner 2020).

Genetic testing finds the mutations in more than 85% of patients, a rate that varies with ethnic origin (Eggermann 2012). A rarer condition, the hypotonia-cystinuria syndrome, comes from a deletion on chromosome 2 that removes SLC3A1 together with a neighbouring gene, PREPL (Eggermann 2012).

How Common It Is

A 2025 review estimates the mean worldwide frequency of cystinuria at 1 in 7,000, with "significant ethnogeographic variation in prevalence" (Iuliano 2025). A US review calls it "the most common genetic cause of recurrent kidney stones" (Azer 2023).

Even so, cystine stones are a small share of all stones, because ordinary calcium stones are so common. Figures in the literature differ a little:

• A French national study of 442 patients states that cystinuria causes 1% of stones in adults and 8% in children (Prot-Bertoye 2015).
• A 2008 review states it accounts for "no more than 1% of all urinary tract stones" (Mattoo 2008).
• A Spanish paediatric study gives 2–6% of all urinary stones in children (Quiroz Madarriaga 2022).

The common thread is that cystine stones are rare in adults but make up a noticeably larger share of the stones found in children.

How Cystine Stones Form

A stone forms when more cystine is dissolved in the urine than the urine can hold. Reviews give the solubility limit as about 250 mg of cystine per litre of urine, and describe the goal of treatment as bringing the urinary cystine concentration below that limit (Sakhaee 1994). The same figure, 250 mg/L, is the target written into US tiopronin labels (see the thiol drugs section below). Insoluble cystine falls out of solution as flat, six-sided (hexagonal) crystals that can grow together into larger stones (Mattoo 2008).

Two things move urine away from that limit: more water, which lowers the concentration, and a more alkaline urine, which raises how much cystine can stay dissolved. In the French series, crystals were studied in 89 patients. Compared with urine at pH 6.5 or lower, the odds of cystine crystals were about half at pH 7.0–7.5 (odds ratio 0.52) and about a quarter at pH 7.5–8.0 (odds ratio 0.26). More concentrated urine had the opposite effect: urine with a specific gravity of 1.011–1.014 carried 11 times the odds of cystine crystals seen at 1.005 or below (Prot-Bertoye 2019).

The alkaline side has its own limit. In the same study a urine pH above 8.0 raised the odds of calcium phosphate crystals about six-fold (odds ratio 6.09), which is why the authors set a target of pH above 7.5 "while warning about calcium-phosphate crystallization" (Prot-Bertoye 2019).

How much cystine a person passes does not line up neatly with how many stones they form. The international consortium found that "stone events do not correlate with amino acid urinary excretion" (Dello Strologo 2002).

When Stones Usually Begin

Older reviews state that cystine stones "frequently occur in the second or third decade of life, with an occasional occurrence in infancy and in old age" (Sakhaee 1994). The French national series gives the most detailed figures: the median age at first symptoms was 16.7 years, but the range ran from 0.3 to 72.1 years, and the median delay before diagnosis was 1.3 years, with some people waiting up to 45.7 years (Prot-Bertoye 2015).

In a US children's hospital cohort of 23 patients, the median age at presentation was 12 years. Pain was the commonest first symptom (13 of 23), followed by nausea or vomiting, visible blood in the urine and fever; one child arrived with acute kidney failure (Varda 2016). A case report from Spain describes the opposite end: an elderly man with no earlier stone history whose first episode of colic led to the diagnosis (Pierna 2020).

The disease is more severe in males than in females, according to the international consortium's clinical data (Dello Strologo 2002).

How It Is Diagnosed

Sources describe three main routes to the diagnosis:

• Crystals in the urine. Flat hexagonal crystals seen under the microscope are described as typical of cystine. In the Spanish case report, the sediment showed "abundant flat and hexagonal crystals", and amino acid analysis then confirmed high cystine and dibasic amino acid levels (Pierna 2020). The case report's authors call these crystals pathognomonic, meaning they point to this one disease (Pierna 2020).
• Stone analysis. A 2020 review lists family history, analysis of a passed or removed stone, and measurement of urinary cystine as the ways cystinuria is diagnosed (Moussa 2020).
• 24-hour urine cystine. Reviews state that a urinary cystine excretion above 250 mg per gram of creatinine is "usually diagnostic of homozygous cystinuria" (Sakhaee 1994).

Genetic testing of SLC3A1 and SLC7A9 confirms the type, and the European recommendation covers when it is used (Servais 2021; Eggermann 2012). Brothers and sisters of a known patient are often tested: in the US children's cohort five patients were found through sibling screening, and four of those five were managed with medical treatment alone (Varda 2016).

For follow-up, recent reviews describe a test called cystine capacity, which measures whether a person's urine can still dissolve added cystine (a positive number) or is already oversaturated and drops cystine out (a negative number). Reviewers treat it as a key recent advance in monitoring (Azer 2023; Zambudio Munuera 2026).

Fluid and Urine Alkalinisation

Both the 2020 US consensus statement and the 2021 European recommendation describe a step-by-step approach. It begins with fluid intake and diet changes; if stones keep forming, the next step is to make the urine more alkaline, and the step after that is a cystine-binding thiol drug (Eisner 2020; Servais 2021).

Fluid

A French centre followed 27 adults for a mean of 11.6 years on high fluid intake and alkali, with a thiol drug added when stones kept forming. Fifteen patients needed no further stone procedures. The patients whose stones stopped had a mean urine volume of 3,151 mL a day, against 2,446 mL a day in those whose stones continued, and the authors concluded that a daily urine volume above 3 litres is "essential for therapeutic success regardless of whether thiol derivatives are administered" (Barbey 2000). A 2024 systematic review of 14 studies reports that first-line therapy raised urine volume above 3 L a day and pH above 7.0 and was associated with less stone formation (Bhatt 2024).

Alkali

Because urinary sodium and cystine rise together, potassium citrate has become the preferred sodium-free alkali, according to a Swedish research group (Fjellstedt 2001). Their study in 14 patients compared it with sodium bicarbonate, two weeks on each. Both raised urine pH to a similar degree, but sodium bicarbonate raised urinary sodium. Plasma potassium was higher on potassium citrate and one patient developed mild hyperkalaemia (5.0 mmol/L); the authors limited their conclusion to people without severe kidney impairment (Fjellstedt 2001).

Stomach and bowel side effects were reported in 12.3% of French patients on potassium bicarbonate, 10.4% on potassium citrate and 2.6% on sodium bicarbonate (Prot-Bertoye 2019).

Salt and Protein in the Diet

A 2008 review lists "dietary restriction of salt and animal protein" among the standard prevention measures (Mattoo 2008), and both guideline documents include diet in their first step (Eisner 2020; Servais 2021). One reason given is that cystine transport across the kidney tubule is coupled to the transport of sodium (Lindell 1995).

The direct evidence is small and not fully consistent:

• Sodium, 1995. In a Swedish study of 13 patients put on sodium-restricted diets, free cystine excretion rose by 3.1 µmol (0.75 mg) a day for each extra millimole of urinary sodium (Lindell 1995).
• Sodium and protein, 2025. An Italian cohort followed 41 adults with recurrent cystine stones through five 24-hour urine collections each. About 10 g a day more protein was associated with 164 µmol a day more cystine excretion. About 1 g a day more salt was associated with a non-significant 46 µmol a day rise. The authors concluded that protein has a moderate effect, salt a minimal one, and that fluid and alkali remain the main levers (Bermond 2025).

No trial was found that tested a particular diet pattern against stone recurrence in cystinuria. Lysine shares the faulty transporter; the theoretical question of lysine supplements in cystinuria is discussed on the lysine and arginine page.

Thiol Drugs: Tiopronin and D-Penicillamine

Thiol drugs carry a reactive sulfur group. They split cystine into two halves and bond to one of them, forming a "mixed disulfide" that leaves in the urine in place of free cystine (Harbar 1986; Moussa 2020). The two in long use are tiopronin (called alpha-mercaptopropionylglycine in older papers) and D-penicillamine.

How well they work

• A 1986 British comparison measured tiopronin as about one and a half times as effective as D-penicillamine at lowering free urinary cystine (Harbar 1986).
• A 1986 US study gave tiopronin long term to 66 patients at an average dose of 1,193 mg a day. Urinary cystine was kept below saturation, stone formation stopped in 63–71% of patients and the individual stone rate fell in 81–94% (Pak 1986).
• In 11 American children whose D-penicillamine dose was raised gradually, urinary cystine concentration fell by a mean of 54%, only 2 had significant side effects over a mean of 109 months, and no child had stones while taking the drug as directed (DeBerardinis 2008).
• Against those results, the French series of 442 patients found that tiopronin and D-penicillamine did not reduce the risk of cystine crystals in urine, whereas higher pH and more dilute urine did (Prot-Bertoye 2019).

Side effects

• In the 1986 US study, side effects affected 75.5% of patients on tiopronin who had taken D-penicillamine before and 64.7% of those who had not, against 83.7% who had toxicity on D-penicillamine. Among patients who took both drugs, 30.6% had to stop tiopronin and 69.4% could not tolerate D-penicillamine (Pak 1986).
• In the French series, 24.6% of patients on tiopronin and 29.5% on D-penicillamine had at least one adverse event, a difference that was not significant (Prot-Bertoye 2019).
• Kidney injury from protein leakage is a known risk. A 3-year-old boy developed nephrotic syndrome (swelling, low urine output and heavy protein loss in the urine) nine months after starting tiopronin; it resolved within 10 days of stopping the drug (Tasic 2011).
• A review of US adverse-event reports from 2014 to 2025 found 1,838 tiopronin cases, 69.6% in children. Besides the known effects, it flagged signals not on the label: reduced sense of smell, skin thinning, breath odour, tongue discoloration and wrong doses being given, the last of particular concern in children (Ergül 2026).
• A 2026 review states that discontinuation rates for thiol drugs have been reported at 30–50% (Zambudio Munuera 2026).

What the US tiopronin labels state

The US Food and Drug Administration (FDA) labels for tiopronin, read for this page, state the following:

• Use: with high fluid intake, alkali and diet change, to prevent cystine stones in adults and children with severe homozygous cystinuria "who are not responsive to these measures alone". Depending on the product, the children's indication is set at 20 kg body weight or at 9 years of age.
• Dose stated on the label: 800 mg a day to start in adults, with an average of about 1,000 mg a day in the clinical studies; 15 mg/kg a day to start in children, with doses above 50 mg/kg a day linked to a higher risk of proteinuria. The daily dose is split into three.
• Monitoring: urinary cystine measured one month after starting and every three months after that, with the dose adjusted to keep urinary cystine below 250 mg/L; urine protein checked before treatment and every 3 to 6 months.
• Warnings: proteinuria, including nephrotic syndrome and membranous nephropathy, and hypersensitivity reactions (drug fever, rash, joint pain and swollen lymph nodes). The label directs that the drug be stopped if proteinuria develops.
• Commonest adverse reactions (10% or more): nausea, diarrhoea or soft stools, mouth ulcers, rash, fatigue, fever, joint pain, proteinuria and vomiting. Reduced taste perception is also listed.
• Breastfeeding: the label states that breastfeeding is not recommended during treatment and that a published study suggests tiopronin may suppress milk production.

The Captopril Evidence

Captopril is a blood pressure drug (an angiotensin-converting enzyme inhibitor) that, like tiopronin, carries a sulfur group. It can form a captopril–cysteine compound that, according to a 1987 report, is 200 times more soluble than cystine (Sloand 1987). The evidence pulls in both directions:

• Reports of benefit. In two siblings, cystine excretion fell by 70% and 93% (Sloand 1987). In seven patients given captopril on top of fluid and alkali, mean cystine excretion fell from 744 to 371 mg per gram of creatinine, ranging from 18% to 89% of each person's starting level (Streem 1989). Two patients who could not tolerate standard treatment had no new stones and no side effects over one year on captopril (Perazella 1993).
• Reports of no effect. Published letters carry the titles "Cystinuria: failure of captopril to reduce cystine excretion" (Dahlberg 1989) and "Captopril is not clinically useful in reducing the cystine load in cystinuria or cystinosis" (Coulthard 1991).

All of these are case reports, letters or small uncontrolled series. No randomised trial of captopril in cystinuria was found for this page.

Surgery to Remove Stones

Most people with cystinuria have at least one stone operation. In the French national series, 81.8% had undergone at least one urological procedure (Prot-Bertoye 2015). A US study comparing 52 cystine stone formers with 3,215 people with ordinary stones found 4.0 procedures per unit of time at risk before treatment against 1.86 for ordinary stones; on treatment both rates fell, to 0.88 and 0.23 (Worcester 2006).

Cystine stones are hard for shock-wave lithotripsy, the method that breaks stones from outside the body (Worcester 2006). The methods described in the literature are therefore mainly:

• Ureteroscopy with laser — a thin scope passed up through the bladder. In a Spanish children's series of 22 such operations on 64 stones under 2 cm, 59% of patients were stone-free on ultrasound one month later and complications during surgery occurred in 18.2%; distorted kidney anatomy from earlier stones made 73% of the operations harder (Quiroz Madarriaga 2022).
• Percutaneous nephrolithotomy — removal through a small opening in the back, used for larger stones. A 2026 review describes miniaturised versions and the newer thulium fibre laser as less traumatic options (Zambudio Munuera 2026).
• Open or robotic surgery — now less common. In the US children's cohort, 110 stone procedures were done in 15 of 23 children: 44 ureteroscopies, 13 percutaneous operations and 9 open or robotic operations, including one kidney removal (Varda 2016).

The type of surgery matters for the long run. In a US comparison, a higher number of open stone operations and kidney removal were each linked to higher blood creatinine, a marker of lower kidney function, and 14.1% of cystinuric patients had lost a kidney against 2.9% of calcium oxalate stone formers. The authors concluded that a minimally invasive approach is preferred when stones need removing (Assimos 2002).

Kidney Function and Recurrence

Kidney function

Reviews disagree in tone about the long-term kidney outlook. A 2025 review describes the prognosis as favourable and says kidney failure is brought on "very rarely", mainly by poor adherence, repeated stones and repeated interventions (Iuliano 2025). The large clinical series show a less settled picture:

• In the French national series, 314 patients aged 16 or older had a recent kidney function result. Only 22.5% had normal function (estimated filtration rate of 90 or more); 50.6% had mildly reduced function (60–89), and 26.7% were below 60, the level used to define chronic kidney disease: 15.6% at 45–59, 7.6% at 30–44, 2.9% at 15–29 and 0.6% below 15. High blood pressure was found in 28.6%. Five patients (1.1%) had needed dialysis, at a median age of 35 (Prot-Bertoye 2015).
• In that series, chronic kidney disease was linked to older age, high blood pressure and severe past damage to kidney tissue, such as a previous partial or total kidney removal (Prot-Bertoye 2015).
• The international consortium found kidney function "clearly impaired" in 17% of patients (Dello Strologo 2002).
• A US comparison found a mean blood creatinine of 1.13 mg/dL in cystinuric patients against 1.01 in calcium oxalate stone formers; 5.8% against 2.2% had an abnormally high level (Assimos 2002).
• A Chicago programme measured creatinine clearance, adjusted for age and sex, at 91 L a day in cystine stone formers against 160 L a day in ordinary stone formers at entry; the gap remained at the last measurement (Worcester 2006).

Recurrence

• On treatment, stones become less frequent. In the French single-centre study, stone episodes fell from 0.93 to 0.20 per patient-year and procedures from 0.29 to 0.14 per patient-year once a regular programme began (Barbey 2000).
• But recurrence remains common. In the same study 12 of 27 patients still needed between 1 and 7 procedures each (Barbey 2000). Preliminary data from a European registry of 269 patients in 29 specialist centres showed that only 16.3% reached the target urine pH, 55.2% were above the 250 mg/L urinary cystine threshold, and about 39% had a new stone event within the previous 12 months (Zambudio Munuera 2026).

Newer Agents Under Study

Because the standard drugs are often poorly tolerated, several new approaches are being tested. None has reached a randomised trial with stone outcomes in people.

Alpha-lipoic acid — evidence: mice and two case reports

Alpha-lipoic acid is a nutritional supplement. In a mouse model lacking the SLC3A1 gene, it prevented cystine stones by making urinary cystine more soluble (Zee 2017). Two children aged 6 and 15, already taking potassium citrate, were given alpha-lipoic acid; both tolerated it, their urine's cystine capacity improved, and in one an existing stone disappeared after two months (Cil 2020). A 2026 study in a new mouse model carrying the commonest human SLC7A9 mutation found that alpha-lipoic acid reduced stone burden and inflammation in mice but also caused damage to the lining of the urinary tract (Bhatt 2026).

Tolvaptan — evidence: mice and an eight-day pilot

Tolvaptan blocks the hormone that makes the kidneys hold on to water, so it produces very large volumes of dilute urine. In mice with cystinuria it increased urine volume and slowed stone growth over 30 days (Bai 2021). In a pilot study of four people aged 13 to 24, eight days of tolvaptan turned cystine capacity from negative to positive in three of the four, and urine volume reached between 2.8 and 11.74 litres a day on the higher dose. Blood salts and liver tests stayed normal, but thirst was extreme, rated 9 out of 10 (Nelson 2020).

Crystal-growth inhibitors — evidence: laboratory and mice

These molecules are designed to stick to the surface of a growing cystine crystal and block further growth. In 2010, microscope studies showed that L-cystine dimethyl ester and L-cystine methyl ester sharply slowed cystine crystal growth in the laboratory (Rimer 2010). A later compound, reported in 2024, was about 120 times more potent than L-cystine dimethyl ester at blocking crystallisation, was absorbed when taken by mouth, and prevented stones in mice lacking SLC3A1 (Hu 2024).

Other ideas

A 2023 review lists cystine mimetics, gene therapy, vasopressin-receptor blockers such as tolvaptan, and sodium–glucose cotransporter 2 inhibitors as future research directions (Azer 2023). A 2026 review calls oral N-acetylcysteine a "rational candidate for formal prospective evaluation" but notes that robust trial evidence in cystinuria is lacking (Zambudio Munuera 2026); the older N-acetylcysteine findings are on the N-Acetylcysteine and Kidney Health page.

What Is Not Known

• The guidelines rest on thin evidence. The European panel's 20 statements "could not be graded" because of the rarity of the disease and the poor level of evidence (Servais 2021). The US consensus found 25 suitable articles out of 2,335 screened (Eisner 2020). A 2023 review notes that the recommendations exist "in the absence of randomized, controlled trials" (Azer 2023).
• Whether thiol drugs prevent crystals in everyday use. Small older studies report fewer stones on tiopronin, while the largest series found no fall in crystal risk on either thiol drug (Pak 1986; Prot-Bertoye 2019).
• How much salt matters. A 1995 study found a clear sodium effect on cystine excretion; a 2025 cohort found a non-significant one (Lindell 1995; Bermond 2025).
• Why stone counts do not follow cystine levels. Stone events did not correlate with amino acid excretion in the international database (Dello Strologo 2002).
• Whether newer agents are safe and effective in people. Alpha-lipoic acid, tolvaptan and crystal-growth inhibitors have only animal studies, case reports or short pilots, and one 2026 mouse study found urinary tract damage from alpha-lipoic acid (Bhatt 2026).
• Whether captopril works. Small reports point both ways and no controlled trial was found.

Key Research Papers

1. Servais A, Thomas K, Dello Strologo L, Sayer JA, Bekri S, Bertholet-Thomas A, Bultitude M, Capolongo G, Cerkauskiene R, Daudon M, Doizi S, Gillion V, Gràcia-Garcia S, Halbritter J, Heidet L, van den Heijkant M, Lemoine S, Knebelmann B, Emma F, Levtchenko E. Cystinuria: clinical practice recommendation. Kidney Int. 2021;99(1):48-58. PubMed PMID: 32918941
2. Eisner BH, Goldfarb DS, Baum MA, Langman CB, Curhan GC, Preminger GM, Lieske JC, Pareek G, Thomas K, Zisman AL, Papagiannopoulos D, Sur RL. Evaluation and Medical Management of Patients with Cystine Nephrolithiasis: A Consensus Statement. J Endourol. 2020;34(11):1103-1110. PubMed PMID: 32066273
3. Calonge MJ, Gasparini P, Chillarón J, Chillón M, Gallucci M, Rousaud F, Zelante L, Testar X, Dallapiccola B, Di Silverio F, et al. Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat Genet. 1994;6(4):420-5. PubMed PMID: 8054986
4. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-91. PubMed PMID: 18359399
5. Scriver CR. Garrod's Croonian Lectures (1908) and the charter 'Inborn Errors of Metabolism': albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. J Inherit Metab Dis. 2008;31(5):580-98. PubMed PMID: 18850300
6. Eggermann T, Venghaus A, Zerres K. Cystinuria: an inborn cause of urolithiasis. Orphanet J Rare Dis. 2012;7:19. PubMed PMID: 22480232
7. 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. Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J Am Soc Nephrol. 2002;13(10):2547-53. PubMed PMID: 12239244
8. Iuliano I, Iervolino A, Suzumoto Y, Shams A, Longobardi C, Capasso G, Perna AF, Capolongo G. Cystinuria: A Genetic and Molecular View - What Is Known about Animal Models and Cells. Kidney Blood Press Res. 2025;50(1):585-596. PubMed PMID: 40562017
9. Azer SM, Goldfarb DS. A Summary of Current Guidelines and Future Directions for Medical Management and Monitoring of Patients with Cystinuria. Healthcare (Basel). 2023;11(5):674. PubMed PMID: 36900678
10. Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Bataille P, Bridoux F, Brignon P, Choquenet C, Cochat P, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N'Guyen HV, Noël C, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M. CKD and Its Risk Factors among Patients with Cystinuria. Clin J Am Soc Nephrol. 2015;10(5):842-51. PubMed PMID: 25717071
11. Quiroz Madarriaga Y, Badenes Gallardo A, Llorens de Knecht E, Motta Lang G, Palou Redorta J, Bujons Tur A. Can cystinuria decrease the effectiveness of RIRS with high-power ho:yag laser in children? Outcomes from a tertiary endourology referral center. Urolithiasis. 2022;50(2):229-234. PubMed PMID: 35084538
12. Sakhaee K. Cystinuria: pathogenesis and treatment. Miner Electrolyte Metab. 1994;20(6):414-23. PubMed PMID: 7783705
13. Prot-Bertoye C, Lebbah S, Daudon M, Tostivint I, Jais JP, Lillo-Le Louët A, Pontoizeau C, Cochat P, Bataille P, Bridoux F, Brignon P, Choquenet C, Combe C, Conort P, Decramer S, Doré B, Dussol B, Essig M, Frimat M, Gaunez N, Joly D, Le Toquin-Bernard S, Méjean A, Meria P, Morin D, N'Guyen HV, Normand M, Pietak M, Ronco P, Saussine C, Tsimaratos M, Friedlander G, Traxer O, Knebelmann B, Courbebaisse M. Adverse events associated with currently used medical treatments for cystinuria and treatment goals: results from a series of 442 patients in France. BJU Int. 2019;124(5):849-861. PubMed PMID: 30801923
14. Varda BK, Johnson EK, Johnson KL, Rosoklija I, Baum MA, Nelson CP. Imaging and surgical utilization for pediatric cystinuria patients: A single-institution cohort study. J Pediatr Urol. 2016;12(2):106.e1-7. PubMed PMID: 26597229
15. Pierna M, Abdelgabar M, Fernández-Rivas R, Fernández-Burriel M. Cystinuria: urine sediment as a diagnostic test. Adv Lab Med. 2020;1(2):20200026. PubMed PMID: 37363779
16. Moussa M, Papatsoris AG, Abou Chakra M, Moussa Y. Update on cystine stones: current and future concepts in treatment. Intractable Rare Dis Res. 2020;9(2):71-78. PubMed PMID: 32494553
17. Zambudio Munuera A, Rodriguez Parras P, Galan Llopis JA, Grases Freixedas F, Cano Garcia MDC, Arrabal-Martin M, Arrabal Polo MA. Cystinuria: Diagnosis, Medical and Surgical Management, and Emerging Therapies. A Narrative Review. Res Rep Urol. 2026;18:629402. PubMed PMID: 42542789
18. Barbey F, Joly D, Rieu P, Méjean A, Daudon M, Jungers P. Medical treatment of cystinuria: critical reappraisal of long-term results. J Urol. 2000;163(5):1419-23. PubMed PMID: 10751848
19. Bhatt NP, Deshpande AV, Starkey MR. Pharmacological interventions for the management of cystinuria: a systematic review. J Nephrol. 2024;37(2):293-308. PubMed PMID: 37957454
20. 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;29(5):295-302. PubMed PMID: 11762790
21. Lindell A, Denneberg T, Edholm E, Jeppsson JO. The effect of sodium intake on cystinuria with and without tiopronin treatment. Nephron. 1995;71(4):407-15. PubMed PMID: 8587620
22. Bermond F, Fabbrini L, Rivoli L, Spasiano A, Leporati M, Petrarulo M, Ricotti A, Borsotti L, Marangella M, Cosseddu D, Ferraro PM, Vitale C. Dietary salt and protein intake and urinary cystine excretion in patients with cystinuria. Clin Kidney J. 2025;18(11):sfaf329. PubMed PMID: 41282358
23. Harbar JA, Cusworth DC, Lawes LC, Wrong OM. Comparison of 2-mercaptopropionylglycine and D-penicillamine in the treatment of cystinuria. J Urol. 1986;136(1):146-9. PubMed PMID: 3712602
24. Pak CY, Fuller C, Sakhaee K, Zerwekh JE, Adams BV. Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol. 1986;136(5):1003-8. PubMed PMID: 3534301
25. DeBerardinis RJ, Coughlin CR 2nd, Kaplan P. Penicillamine therapy for pediatric cystinuria: experience from a cohort of American children. J Urol. 2008;180(6):2620-3. PubMed PMID: 18951580
26. Tasic V, Lozanovski VJ, Ristoska-Bojkovska N, Sahpazova E, Gucev Z. Nephrotic syndrome occurring during tiopronin treatment for cystinuria. Eur J Pediatr. 2011;170(2):247-9. PubMed PMID: 20924604
27. Ergül RB, Gürlek IT, Özervarlı MF, Özcan ŞG, Pietropaolo A, Tsaturyan A, Juliebø-Jones P, Tzelves L, Şener TE, Dönmez Mİ, Oktar T, Somani B, Tefik T. Tiopronin safety in cystinuria: first real-world pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS): an EAU YAU and Endourology sections review. Pediatr Nephrol. 2026;41(4):1087-1095. PubMed PMID: 41263948
28. Sloand JA, Izzo JL Jr. Captopril reduces urinary cystine excretion in cystinuria. Arch Intern Med. 1987;147(8):1409-12. PubMed PMID: 2820331
29. Streem SB, Hall P. Effect of captopril on urinary cystine excretion in homozygous cystinuria. J Urol. 1989;142(6):1522-4. PubMed PMID: 2685368
30. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-7. PubMed PMID: 8488818
31. Dahlberg PJ, Jones JD. Cystinuria: failure of captopril to reduce cystine excretion. Arch Intern Med. 1989;149(3):713, 717. PubMed PMID: 2645847 (letter; no abstract)
32. Coulthard M, Richardson J, Fleetwood A. Captopril is not clinically useful in reducing the cystine load in cystinuria or cystinosis. Pediatr Nephrol. 1991;5(1):98. PubMed PMID: 2025551 (letter; no abstract)
33. Worcester EM, Coe FL, Evan AP, Parks JH. Reduced renal function and benefits of treatment in cystinuria vs other forms of nephrolithiasis. BJU Int. 2006;97(6):1285-90. PubMed PMID: 16686727
34. Assimos DG, Leslie SW, Ng C, Streem SB, Hart LJ. The impact of cystinuria on renal function. J Urol. 2002;168(1):27-30. PubMed PMID: 12050485
35. Zee T, Bose N, Zee J, Beck JN, Yang S, Parihar J, Yang M, Damodar S, Hall D, O'Leary MN, Ramanathan A, Gerona RR, Killilea DW, Chi T, Tischfield J, Sahota A, Kahn A, Stoller ML, Kapahi P. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Med. 2017;23(3):288-290. PubMed PMID: 28165480
36. Cil O, Perwad F. α-Lipoic Acid (ALA) Improves Cystine Solubility in Cystinuria: Report of 2 Cases. Pediatrics. 2020;145(5):e20192951. PubMed PMID: 32245805
37. Bhatt NP, Nguyen TTH, Iacono G, Rodriguez GR, Anderson CRB, Perry A, Barlow CK, Anderson D, Burgio G, Marsland BJ, Jiang SH, Deshpande AV, Starkey MR. Generation of a novel Slc7a9(G105R) mutant mouse identifies new biomarkers for cystinuria. Kidney Int. 2026;110(5):1204-1224. PubMed PMID: 42612871
38. Bai Y, Tang Y, Wang J, Wang X, Wang Z, Cao D, Han P, Wang J. Tolvaptan treatment of cystine urolithiasis in a mouse model of cystinuria. World J Urol. 2021;39(1):263-269. PubMed PMID: 32189089
39. Nelson CP, Kurtz MP, Venna A, Cilento BG Jr, Baum MA. Pharmacological Dilutional Therapy Using the Vasopressin Antagonist Tolvaptan for Young Patients With Cystinuria: A Pilot Investigation. Urology. 2020;144:65-70. PubMed PMID: 32683063
40. Rimer JD, An Z, Zhu Z, Lee MH, Goldfarb DS, Wesson JA, Ward MD. Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design. Science. 2010;330(6002):337-341. PubMed PMID: 20947757
41. Hu L, Albanyan H, Yang J, Wang Y, Yang M, Tan X, Zhong X, Ward MD, Sahota A. 8-l-Cystinyl Bis(1,8-diazaspiro[4.5]decane) as an Orally Bioavailable l-Cystine Crystallization Inhibitor for Cystinuria. ACS Med Chem Lett. 2024;15(7):1026-1031. PubMed PMID: 39015267

PubMed Topic Searches

1. PubMed: cystinuria
2. PubMed: cystinuria and tiopronin
3. PubMed: cystinuria and chronic kidney disease
4. PubMed: cystinuria genes SLC3A1 and SLC7A9
5. PubMed: cystine stone surgery
6. PubMed: cystinuria and alpha-lipoic acid

Connections

• Nephrology & Hepatology — the kidney and liver section
• Kidney Stones — every stone type, and how they are treated
• Oxalate Nephropathy — crystal damage inside the kidney tissue
• Primary Hyperoxaluria — another inherited cause of stones that starts young
• Kidney Disease — chronic kidney disease, a long-term risk in cystinuria
• Cysteine: History — how cystine was found in a bladder stone
• N-Acetylcysteine and Kidney Health — the thiol supplement's cystine evidence
• Lysine and Arginine — the amino acids that share the faulty transporter
• How Kidney Stones Form — an interactive animation

Featured Videos