MANAGEMENT OF CYSTINE STONE

Mohammed Taher Aldoukhi,MD

EVIDENCE AND RECOMMENDATION BY EAU

CYSTINURIA

Cystinuria is an autosomal-recessive defect in

reabsorptive transport of cystine and the dibasic

amino acids ornithine, arginine, and lysine from the

luminal fluid of the renal proximal tubule and small

intestine. The only phenotypic manifestation of

cystinuria is cystine urolithiasis

1 in 7000 births

1-2% of all stone formers

Up to 5% in pediatric stone formers

PATHOPHYSIOLOGY

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PATHOPHYSIOLOGY

Renal transport of cystine• Amino acids filtered undergo nearly complete reabsorption by

proximal tubular cells.

• Only 0.4% of the filtered cystine appears in the urine.

• . At least 2 transport systems are responsible for cystinereabsorption, as follows:

- High-affinity system:

This system is affected in persons with cystinuria.

Mediates uptake of 10% of cystine and the dibasic

amino acids at the third segment (S3) of the proximal

tubule.

- Low-affinity system:

: This system is present in the (S1-S2)

part of the proximal tubule and is responsible for 90%

of cystine reabsorption.

PATHOPHYSIOLOGY (CONT)

Intestinal transport of cystine

The high-affinity transporter is present in the apical

brush-border membrane of the jejunum and is

responsible for absorption of cystine and dibasic

amino acids.

PATHOPHYSIOLOGY (CONT)

Normally, cystine and the other dibasic amino acids

(ie, ornithine, lysine, arginine) are filtered at the

glomerulus and reabsorbed in the proximal

convoluted tubule

. Defects in this channel cause elevated levels of

dibasic amino acid secretion in the urine.

Whereas ornithine, lysine, and arginine are

completely soluble, cystine is relatively insoluble at

physiologic urine pH levels of 5-7

PRESENTATION

Presentation is similar to that of other types of renal

calculi and includes renal colic, chronic urinary tract

infections in a young person with a family history of

renal stones, passage of stones or gravel,

hematuria, and dysuria.

DIAGNOSIS

Diagnostic confirmation:

Positive family history of cystinuria

Stone analysis showing cystine

Identification of pathognomonic hexagonal cystine

crystals on urinalysis

A positive cyanide-nitroprusside screen indicates a

urinary cystine concentration >75 mg/L

Quantitative 24-h urinary cystine excretion more

than 30 mg/day are considered abnormal

:CYSTINE STONE CHARACTERISTICS

Poor radiopacity

visualized with non-contrast CT

SWL-resistant stones

Two thirds of persons with cystinuria who form

stones make pure cystine calculi

One third have a mixture of cystine and calcium

oxalate calculi.

MANAGEMENT

TREATMENT :

The aim of medical therapy is to maintain the

cystine concentration in the urine below its solubility

level

solubility of cystine in urine from 175 to 360 mg/L ≈

about 243 mg/L

avoiding cystine crystallisation is to maintain urine

pH

between 7.5. and 8.5

TRAETMENT (CONSERVATIVE)

High fluid intake

Sodium and protein restriction

Urinary alkalinization

RESISTANT TO CONSERVATIVE THERAPY

Cystine is formed from the linkage of two cysteine

molecules by a disulfide bond

sulfhydryl groups that can reduce this disulfide bond,

producing mixed disulfides with cysteine that are

more soluble than cystine

PHARMACOLOGICAL SUBSTANCES

S/E:fever, rash,

abnormal taste,

arthritis,

leukopenia,

aplastic anemia,

hepatotoxicity,

and pyridoxine

deficiency. In

addition,

proteinuria

dose range is

0.5 to 2

g/day, given

in three to

four divided

doses

decreases

stone size or

dissolves

stones in up

to 75 %

forms a

penicillamine-

cysteine

disulfide that is

50 times more

soluble than

cystine

D-

penicillamine

same but

incidence of

these side

effects is

lower than

with

penicillamine

400 to 1200

mg/day in

three divided

doses

decreases

stone size or

dissolves

stones in up to

70 %

forms a

tiopronin-

cysteine

disulfide

Tiopronin

(thiola)

Headache, dry

cough,

flushing

150 mg/dayto treat

patients with

cystinuria who

are

hypertensive.

sulfhydryl

groups, and

form captopril-

cysteine

Captopril

showed a low

toxicity

available only

in Japan and

South Korea

Bucillamine

SURGICAL PROCEDURES

Indications:

Large calculi that are unlikely to dissolve

Obstructing or otherwise symptomatic calculi.

The ultimate goal of surgery is to make the patient

free of stones. While the risk of recurrence is

unchanged

SURGICAL OPTIONS

ESWL

retrograde endoscopic lithotripsy and extraction,

percutaneous nephrolithotomy

percutaneous irrigation chemolysis

open surgery

REFERENCES

http://emedicine.medscape.com/article/435678-overview#showall

http://www.uptodate.com/contents/cystine-stones

http://emedicine.medscape.com/article/435678-clinical#showall

http://www.uroweb.org/guidelines/online-guidelines/

http://emedicine.medscape.com/article/435678-treatment#showall

Mohammed aldoukhi,MD