Cystine stones

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

Mechanism of Action A heavy metal antagonist that chelates copper, iron, mercury, lead to form complexes, promoting excretion of copper. Combines with cystine-forming complex, thus reducing concentration of cystine to below levels for formation of cystine stones. Exact mechanism for rheumatoid arthritis is unknown. May decrease cell-mediated immune response. May inhibit collagen formation. Therapeutic Effect Promotes excretion of copper, prevents renal calculi, dissolves existing stones, acts as anti-inflammatory drug. 

H6. Harris, H., and Warren, F. L., Quantitative studies on urinary cystine in patients with cystine stone formation and their relatives. Ann. Eugenics 18, 125-171 (1953). 

E-7) Cystinuri. -This is a genetic disease affecting epithelial cell transport of cystine and certain other amino acids, resulting in cystine excess and cystine stones in the urine. 

Thibert, R. Dubuc, B. Dufour, M. Tawashi, R. Evaluation of the surface roughness of cystine stones using a visible laser diode scattering approach. Scanning Microsc. 1993, 7 (2), 555-561. 

The normal urinary excretion of cystine has been reported to be 4.81 to 48.1mg/24 hours (40 to 400p.mol/24 hours).Its relatively low limit of solubility, 18.0mg/dL (1500 LlmoI/L), is exceeded in many patients with cystin-uria, resulting in the formation of hexagonal crystals and, ultimately, cystine stones. Cystine stones are usually only seen in homozygotes, although there is some evidence that heterozygotes are at increased risk of stone formation. Cystinuria may present at any age from infancy to old age, although presentation is most common in the second and third decades. 

The finding of a cystine stone should prompt confirmation of cystinuria by urinary analysis. It could be argued, however, that aU stone formers should be screened for cystinuria at least 10% of cystinurics form stones in which cystine cannot be detected, presumably because of epitaxis. The index of suspicion shordd be increased in patients who are relatively young stone formers and in those with a positive family history. Once a cystinuric patient is diagnosed, it is important to screen all members of the family, particularly to detect affected siblings. 

Cystine stones are rare except in cases of an inborn error of metabolism (cystinuria). Cystine, like uric acid, is more soluble in alkaline urine that in acidic urine. Xanthine stones are very rare except in cases of an inborn error of metabolism (xanthinuria). 

Tiopronin, a thiol compound that stabilizes the cystine moiety, is used in prevention of urinary cystine stone formation in patients with severe homozygous cystinuria (urinary cystine excretion exceeding 500 mg daily) unresponsive to other therapies. 

Cystinuria and cystinosis are disorders involving two different transport proteins for cystine, the disulfide formed from two molecules of cysteine. Cystinuria is caused by a defect in the transport protein that carries cystine, lysine, arginine, and ornithine into intestinal epithelial cells and that permits resorption of these amino acids by renal tubular cells. Cystine, which is not very soluble in the urine, forms renal calculi (stones). Cal Kulis, a patient with cystinuria, developed cystine stones (see Chapter 37). 

Kidney stone sufferers may benefit from a diet that produces an acid urine. Uric acid and cystine stones are formed under acidic conditions, and an alkaline-residue diet counters this. Most fruits and vegetables produce an alkaline ash, but... 

Cystinuria is an autosomal recessive disorder of renal mbular teab-sorption of cystine, ornithine, arginine and lysine (mnemonic COAL). Cystine (a dimer of cysteine Chapter 6) is sparingly soluble and accumulates in the tubular fluid, forming bladder and kidney stones (cystine urolithiasis). Cystine is so-called because cystine stones were discovered in the cyst (i.e. bladder). 

Fig. 3-66. Cystinuria. Cystine stone assuming shape of calices...

Cystin stones may develop as small stones or also assume a staghorn configuration. Because of their sulfur content, they are less opaque than calcium stones. The density is typically homogeneous, similar to that of ground glass (Fig. 20.5) (Dyer and Zagoria 1992 Dyer et al. 1998). 

Many pelvic or ureteral stones do not require any intervention and may pass spontaneously, helped by a large urine volume, physical activity, and spasmolytics, if needed. An intervention is required in the case of persisting or severe obstruction or infection. Small calculi, smaller than 5 mm, maybe left in situ and observed. Only two kinds of stones can be dissolved chemically cystine stones by chelating agents and uric acid by alkalization and administration of allopurinol (Chow and Streem 1996). 

The fundamental techniques of nephrostomy insertion, track dilatation, and stent insertion have led to the development of more sophisticated endou-rologic procedures. The initial percutaneous technique developed was for removal of renal calculi. Within a short time, techniques for treatment of ureteropelvic junction and ureteral strictures were developed. Today percutaneous nephrolithotomy has been replaced in many situations by extracorporeal shock wave lithotripsy (ESWL) and uretero-scopic techniques. However, nonoperative management of staghorn calculi, infected lower pole calculi, or cystine stones via percutaneous nephrolithotomy and lithotripsy is still indicated. 

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