Master Cystinuria with Picmonic for Medicine

Cystinuria is inherited in an autosomal recessive manner.

The primary pathophysiologic mechanism underlying cystinuria is a defective amino acid transporter in the proximal tubules of the nephrons in the kidneys. This defect arises from genetic mutations in the SLC3A1 and/or SLC7A9 genes. As a result, the reabsorption of basic, positively charged amino acids is impaired, leading to high levels of these amino acids in the urine.

COLA is an acronym for the amino acids that are unable to be reabsorbed in this disease: (dibasic) cystine, ornithine, lysine, and arginine.

Cystine is not technically an amino acid, it is a dimer of cysteine molecules linked by a disulfide bond. In this dibasic form, cystine is poorly soluble in urine and may precipitate, forming cystine stones in individuals with cystinuria.

Ornithine is an amino acid involved in important biochemical pathways in the body, including the urea cycle. However, it is not typically incorporated into proteins. In cystinuria, ornithine is not reabsorbed in the kidney's proximal tubule, leading to its presence in the urine.

Lysine is a basic amino acid that is not properly reabsorbed due to a defect in the kidney transporter in individuals with cystinuria.

Arginine is a basic amino acid that is not properly reabsorbed due to a defect in the kidney transporter in individuals with cystinuria.

Cystine can precipitate out of urine due to its poor solubility and form kidney stones (nephrolithiasis) in individuals with cystinuria. This can lead to classical kidney stone symptoms, such as flank pain, often associated with renal colic. It is characterized by a severe, sudden onset of sharp pain that radiates from the flank to the lower abdomen or groin. It may also cause hematuria, nausea, vomiting, and urinary urgency or frequency as the stone moves through the urinary tract.

Staghorn kidney stones are large stones in the upper urinary tract that occupy the renal pelvis and extend into at least two of the calyces. While all types of urinary stones can form staghorn calculi, the majority are composed of a struvite-carbonate-apatite matrix, commonly due to urease-producing urinary tract infections such as Proteus mirabilis, which is known to produce urease. In patients with cystinuria, extensive precipitation of cystine out of the urine can also lead to the formation of staghorn calculi.

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.

Recurrent urinary tract infections (UTIs) in cystinuria occur due to the alkaline environment created by the precipitation of cystine in the urine. Urine stasis created by this environment is ideal for bacteria to thrive. Also, cystine stones can irritate the urinary tract, making it more susceptible to infections.

The cyanide nitroprusside test is a urinalysis test used to detect cystine in the urine. In this test, cyanide nitroprusside is added to the urine, and a purple color develops if cystine is present. The cyanide nitroprusside reagent reacts with the disulfide bonds in cystine, resulting in a color change that indicates the presence of cystine in the urine.

High fluid intake (>3 L/day) to dilute urine. Good hydration is a universal management and prevention of kidney stones.

Acidic urine favors cystine precipitation; therefore, alkalinizing the urine is a key component of treatment to prevent stone formation in cystinuria. For alkalizing agents, potassium citrate, which is the preferred drug of choice, and acetazolamide in selected cases are used.

Penicillamine treats cystinuria by acting as a chelating agent that binds to cystine in the urine and forms a soluble complex. Penicillamine-cysteine disulfide is much more water-soluble than cystine. This reduces the precipitation of cystine and prevents the formation of kidney stones.