The main pathophysiologic mechanism behind cystinuria is a defective amino acid transporter in the proximal tubule of nephrons in the kidney. These defective proteins are due to genetic mutations in the SLC3A1 and/or SLC7A9 genes. As a consequence, appropriate reabsorption of basic or positively charged amino acids is prevented.
COLA is an acronym for the amino acids that are unable to be reabsorbed in this disease: (dibasic) cysteine, ornithine, lysine, and arginine.
Cystine is not technically an amino acid. It is a dimer of cysteine amino acids. In this dibasic form, cystine is unable to be reabsorbed and thus may precipitate in the urine as cystine stones.
Ornithine is also technically not an amino acid. However, it is an important molecule for biochemical pathways in the body including the urea cycle. Ornithine is not reabsorbed in the proximal tubule of the kidney in cystinuria.
Lysine is a basic amino acid that is not reabsorbed due to the defect in kidney transporter.
Arginine is a basic amino acid that is not reabsorbed due to the defect in kidney transporter.
Cystine can precipitate out of urine and form kidney stones (nephrolithiasis).
Microscopically, cystine precipitates as hexagonal crystals. A urinalysis can be performed to look for these crystals and aid in diagnosis.
Staghorn kidney stones are upper urinary tract stones that involve the renal pelvis and extend into at least two of the calyces. All types of urinary stones can potentially form staghorn calculi but the majority are composed of struvite-carbonate-apatite matrix. Patients with cystinuria can form staghorn calculi due to extensive precipitation of cystine out of the urine.
Cyanide nitroprusside test is a urinalysis test used to identify cystine present in the urine. In this test, cyanide nitroprusside is added to urine and left alone for approximately 10 minutes. In this time, disulfide bonds within cystine molecules will be broken by the cyanide, releasing cysteine amino acids and changing the urine to a purple color. Therefore a color change indicates the presence of urinary cystine.
Acidic urine favors cystine precipitation. Therefore, treatment with acetazolamide, a diuretic that alkalinizes urine, can be used to help prevent stone formation in cystinuria.
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