Abstract
Cystine stones are an uncommon form of kidney stones but carry high morbidity. They occur in patients with cystinuria, a rare genetic defect in tubular reabsorption of cationic amino acids leading to high amounts of cystine amino acids in urine. Inheritance is autosomal and two major genetic types have been identified. Cystine nephrolithiasis and related kidney diseases are usually the only clinically pertinent manifestation of this disorder.
These patients, mostly presenting in their teens, frequently have a high stone burden and high recurrence rate of kidney stones. Compared with the other more common forms of kidney stones, these patients require a much higher number of invasive procedures and are at higher risk for chronic kidney disease.
Diagnosis is made by stone analysis and measurement of very high cystine levels in urine. Medical management of these stones is successful at reducing the rate of recurrence and the need for surgical procedures but requires high compliance with dietary and pharmacological interventions as well as close follow-up. Cystine capacity is a new urine assay, which is used as a measure of cystine saturation in urine and is helpful in guiding the ongoing management of cystine stones.
The goal of therapy is to modify the urinary milieu to increase solubility of cystine and may include drugs that bind cystine in urine. Dietary management is critical with focus on increasing the urine volume and pH. Pharmacological therapy with urine alkalizing agents and cystine-binding thiol drugs (CBTDs) is often utilized. The two CBTDs, D-penicillamine and tiopronin, are effective agents but require close monitoring due to the need for dose titration and high incidence of adverse reactions.
Ongoing research may help develop newer therapeutic options in the future for this disease with high medical and psychosocial morbidity.
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References
Pereira DJ, Schoolwerth AC, Pais VM. Cystinuria: current concepts and future directions. Clin Nephrol. 2015;83(3):138–46.
Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181–91.
Fotiadis D, Kanai Y, Palacin M. The SLC3 and SLC7 families of amino acid transporters. Mol Asp Med. 2013;34(2–3):139–58.
Chillaron J, et al. Pathophysiology and treatment of cystinuria. Nat Rev Nephrol. 2010;6(7):424–34.
Fattah H, Hambaroush Y, Goldfarb DS. Cystine nephrolithiasis. Transl Androl Urol. 2014;3(3):228–33.
Lambert EH, et al. Analysis of 24-hour urine parameters as it relates to age of onset of cystine stone formation. J Endourol. 2010;24(7):1179–82.
Dello Strologo L, et al. Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. J Am Soc Nephrol. 2002;13(10):2547–53.
Rhodes HL, et al. Clinical and genetic analysis of patients with cystinuria in the United Kingdom. Clin J Am Soc Nephrol. 2015;10(7):1235–45.
Cranidis AI, et al. Cystine stones: the efficacy of percutaneous and shock wave lithotripsy. Urol Int. 1996;56(3):180–3.
Worcester EM, et al. Reduced renal function and benefits of treatment in cystinuria vs other forms of nephrolithiasis. BJU Int. 2006;97(6):1285–90.
Assimos DG, et al. The impact of cystinuria on renal function. J Urol. 2002;168(1):27–30.
Modersitzki F, et al. Health-Related Quality of Life (HRQoL) in cystine compared with non-cystine stone formers. Urolithiasis. 2014;42(1):53–60.
Prot-Bertoye C, et al. CKD and its risk factors among patients with cystinuria. Clin J Am Soc Nephrol. 2015;10(5):842–51.
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.
Eggermann T, et al. Clinical utility gene card for: cystinuria. Eur J Hum Genet. 2012;20(2):1–2.
Knoll T, et al. Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol. 2005;20(1):19–24.
Moses R, et al. Changes in stone composition over two decades: evaluation of over 10,000 stone analyses. Urolithiasis. 2015;43(2):135–9.
Stoller ML, et al. Acalculous cystinuria. J Endourol. 1997;11(4):233–8.
Cochat P, et al. Nephrolithiasis related to inborn metabolic diseases. Pediatr Nephrol. 2010;25(3):415–24.
Andreassen KH, et al. How should patients with cystine stone disease be evaluated and treated in the twenty-first century? Urolithiasis. 2016;44(1):65–76.
Masotti A, et al. Gender-related effects on urine L-cystine metastability. Amino Acids. 2014;46(2):415–27.
Finocchiaro R, et al. Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure. Urol Res. 1998;26(6):401–5.
Giugliani R, Ferrari I, Greene LJ. An evaluation of four methods for the detection of heterozygous cystinuria. Clin Chim Acta. 1987;164(2):227–33.
Barbey F, et al. Medical treatment of cystinuria: critical reappraisal of long-term results. J Urol. 2000;163(5):1419–23.
Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041–7.
Rogers A, et al. Management of cystinuria. Urol Clin North Am. 2007;34(3):347–62.
Rodman JS, et al. The effect of dietary protein on cystine excretion in patients with cystinuria. Clin Nephrol. 1984;22(6):273–8.
Jaeger P, et al. Anticystinuric effects of glutamine and of dietary sodium restriction. N Engl J Med. 1986;315(18):1120–3.
Meschi T, et al. The effect of fruits and vegetables on urinary stone risk factors. Kidney Int. 2004;66(6):2402–10.
Torres VE, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407–18.
de Boer H, Roelofsen A, Janssens PM. Antidiuretic hormone antagonist to reduce cystine stone formation. Ann Intern Med. 2012;157(6):459–60.
Pak CY, et al. Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol. 1986;136(5):1003–8.
Moe OW, Pearle MS, Sakhaee K. Pharmacotherapy of urolithiasis: evidence from clinical trials. Kidney Int. 2011;79(4):385–92.
Chow GK, Streem SB. Medical treatment of cystinuria: results of contemporary clinical practice. J Urol. 1996;156(5):1576–8.
Xu H, et al. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013;14(4):435–47.
Hall CL, et al. Natural course of penicillamine nephropathy: a long term study of 33 patients. Br Med J (Clin Res Ed). 1988;296(6629):1083–6.
Habib GS, et al. Penicillamine and nephrotic syndrome. Eur J Intern Med. 2006;17(5):343–8.
Ntoso KA, et al. Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis: successful treatment of two patients and a review of the literature. Am J Kidney Dis. 1986;8(3):159–63.
Tasic V, et al. Nephrotic syndrome occurring during tiopronin treatment for cystinuria. Eur J Pediatr. 2011;170(2):247–9.
Cohen TD, Streem SB, Hall P. Clinical effect of captopril on the formation and growth of cystine calculi. J Urol. 1995;154(1):164–6.
Michelakakis H, et al. Ineffectiveness of captopril in reducing cystine excretion in cystinuric children. J Inherit Metab Dis. 1993;16(6):1042–3.
Asplin DM, Asplin JR. The interaction of thiol drugs and urine pH in the treatment of cystinuria. J Urol. 2013;189(6):2147–51.
Sumorok N, Goldfarb DS. Update on cystinuria. Curr Opin Nephrol Hypertens. 2013;22(4):427–31.
Pietrow P, et al. Durability of the medical management of cystinuria. J Urol. 2003;169(1):68–70.
Pareek G, Steele TH, Nakada SY. Urological intervention in patients with cystinuria is decreased with medical compliance. J Urol. 2005;174(6):2250–2, discussion 2252.
Fjellstedt E, et al. Cystine analyses of separate day and night urine as a basis for the management of patients with homozygous cystinuria. Urol Res. 2001;29(5):303–10.
Haritopoulos K, et al. Impact of a metabolic stone clinic on management of patients with cystinuria: 5 years follow-up. Clin Ter. 2010;161(4):341–4.
Tuso P, et al. Cystinuria and renal transplantation. Nephron. 1993;63(4):478.
Sahota A, et al. Novel cystine ester mimics for the treatment of cystinuria-induced urolithiasis in a knockout mouse model. Urology. 2014;84(5):1249 e9–15.
Lee MH, et al. Cystine growth inhibition through molecular mimicry: a new paradigm for the prevention of crystal diseases. Curr Rheumatol Rep. 2015;17(5):33.
Rimer JD, et al. Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design. Science. 2010;330(6002):337–41.
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Agrawal, N., Zandi-Nejad, K. (2019). Cystine Stones. In: Han, H., Mutter, W., Nasser, S. (eds) Nutritional and Medical Management of Kidney Stones. Nutrition and Health. Humana, Cham. https://doi.org/10.1007/978-3-030-15534-6_12
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DOI: https://doi.org/10.1007/978-3-030-15534-6_12
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