eMedicine Specialties > Pediatrics: General Medicine > Nephrology
Cystinosis: Treatment & Medication
Updated: Aug 31, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
In the past, the treatment of cystinosis was limited to treating metabolic acidosis and, often, replacing electrolytes lost in the urine; later during the course of the disease, chronic kidney disease (CKD) was treated.2 Today, the wide availability of an effective drug, phosphocysteamine, and kidney replacement therapy with transplantation has dramatically improved the outlook for patients and altered management strategies.
- Replacement of urinary losses: The child must be well-hydrated and administered supplements of potassium and bicarbonate, as needed. Rickets should be treated with vitamin D and phosphate supplementation. Carnitine may also be needed because its excretion is particularly elevated in the urine, and muscle levels have been documented to be reduced. Particular care should be given to fluid and electrolyte therapy during intercurrent episodes of fever, vomiting, or diarrhea.
- Management of volume depletion/dehydration states
- Initial management of volume depletion in a child with cystinosis requires administration of large amounts of fluids and electrolytes, often exceeding conventionally defined limits. Fluid requirements may be more than twice that expected for the patient's size.
- Urinary losses must be carefully monitored and replaced during hospitalization.
- The rehydration fluid should contain glucose, sodium, potassium, and bicarbonate (in amounts generously exceeding the standard intravenous fluid composition). The concentration of these substances should be adjusted on the basis of frequently measured serum laboratory values.
- After rehydration is accomplished, maintaining free access to water or other fluids is important because patients with cystinosis easily become dehydrated. For example, place a water container at the bedside during the night.
- When the patient becomes free of acute GI symptoms (ie, no longer having frequent episodes of vomiting, gagging, abdominal pain, or diarrhea) and is able to eat well, restart the patient on a regular diet, supplementing individually determined amounts of sodium, potassium, bicarbonate, and phosphate to achieve reference range serum levels.
- Indomethacin therapy
- Indomethacin may limit water losses in patients with nephropathic cystinosis by both reducing the glomerular filtration rate (GFR) and by sensitizing the collecting duct to the effects of antidiuretic hormone. It has been used to treat patients with cystinosis more commonly in Europe than in the United States. In uncontrolled clinical reports, indomethacin has been shown to relieve polyuria and polydipsia and to improve appetite, energy, and general well-being by reducing urinary losses of water and other various substances.
- Indomethacin therapy requires careful monitoring of kidney function because the GFR may be worsened by the administration of this drug.
- The ulcerogenic potential of indomethacin is its major drawback for treating cystinosis.
- Growth hormone therapy
- Treatment with recombinant human growth hormone improves growth velocity. Long-term recombinant human growth hormone treatment in young children with nephropathic cystinosis prior to renal replacement therapy is safe and efficient.
- Growth hormone treatment is less effective for peripubertal or adolescent patients on renal replacement therapy.
- Treatment with recombinant human growth hormone does not accelerate a decline in kidney function in children with chronic kidney disease.
- Thyroid replacement: This is indicated in patients diagnosed with hypothyroidism.
- Kidney transplantation: Kidney transplantation in patients with infantile cystinosis corrects kidney failure and prolongs survival (the donor parenchymal cells are not homozygous for the genetic defect and are therefore able to transport cystine from the lysosomes). However, transplantation does not prevent progression of the disease in other nonrenal organs, and therapy with phosphocysteamine is indicated in patients after kidney transplantation.
Surgical Care
- Some patients with severe gastroesophageal reflux may require gastric/jejunal tube placement or Nissen fundoplication to achieve optimal nutrition.
Consultations
- Nephrologists usually diagnose cystinosis as the cause of Fanconi syndrome.
- The patient must be referred to an ophthalmologist upon initial evaluation and at subsequent regular intervals.
- A pediatric endocrinologist may provide follow-up care for the patient related to growth hormone therapy, thyroid insufficiency, or diabetes mellitus.
- Patients with recurrent abdominal pain, poor feeding, or vomiting and/or diarrhea should be evaluated by a gastroenterologist to diagnose the nature of GI abnormalities (eg, swallowing dysfunction, gastroesophageal reflux, delayed gastric emptying, gastric/duodenal ulcer, pseudo-obstruction).
- Some children may require follow-up care by a behavioral therapist or a dietitian, depending on the child's needs.
- Because of various neuromuscular problems, patients in late adolescence require follow-up by a neurologist.
Diet
- Dietary recommendations should follow daily Dietary Reference Intake (DRI) requirements (ie, 60% carbohydrate, 10% protein, 30% lipids), and caloric intake should aim to achieve weight gain. If the patient is a poor eater and oral feeding is unsuccessful, high-calorie oral supplements should be administered. If the patient does not take supplements or has an inappropriately low intake because of poor appetite or vomiting, gastric tube placement can help.
- Total parenteral nutrition is indicated if a cystinotic patient cannot tolerate any form of enteral feeding. Some patients may need additional therapy with agents improving GI kinetics or antagonists of acid production.
Activity
Because of the chronic nature of the disorder, parents should try to accommodate the child's medical needs, while allowing the child to grow and develop similar to healthy children. Parents should encourage play and group participation.
Medication
Cysteamine, introduced in the 1980s, blunts the decline in renal function and improves the linear growth of these children, despite the fact that it does not ameliorate the defect in renal tubule transport. Oral cysteamine (Cystagon) therapy should be initiated within days of diagnosis. Cysteamine has to be administered every 6 hours, including the night, to prevent nocturnal accumulation of cystine. Topical cysteamine therapy to the anterior segment of the eye needs to be applied every hour when awake. It is awaiting US Food and Drug Administration (FDA) approval.
Cystine-depleting agents
Cysteamine is an aminothiol compound used to treat cystinosis. Various cysteamine salts are used. Cysteamine HCl has an unpleasant taste and odor, and, therefore, other forms have been developed. Cysteamine bitartrate (Cystagon) is available in the United States. Another form, phosphocysteamine, is the phosphorothioester of cysteamine and is rapidly converted to cysteamine in the gut. Phosphocysteamine is designated as an orphan drug in the United States. Much of the clinical data refers to cysteamine HCl or phosphocysteamine.
In addition to the oral product that is available, an ophthalmic product is currently investigational. Topical cysteamine therapy administered to the anterior segment of the eye is being studied to observe the results of decreasing corneal cystine crystals, which develop with nephropathic cystinosis.
Cysteamine bitartrate (Cystagon)
Approved by the FDA in August 1994, the sole distributor of this drug in the United States is CVS Procare (888-700-0024).
Used as a cystine-depleting agent in cystinosis. It is a weak base that enters the cystinotic lysosome and reacts with cystine, forming a mixed disulfide of half-cystine and cysteamine. This mixed disulfide rapidly exits the lysosome via the transport system for cationic amino acids, which is normal in cystinosis. Cysteamine and its prodrug analog, phosphocysteamine, are very beneficial to patients with cystinosis, especially when started early in life. Therapy does not prevent or affect Fanconi syndrome. Diagnosis of cystinosis as early as possible is important because efficacy of cysteamine or phosphocysteamine treatment clearly relates to age at which the drugs are started.
Goal of therapy is to keep leukocyte cystine levels <1 nmol/half-cystine/mg protein measured 5-6 h following administration of cysteamine. Check cystine levels after maintenance dose is achieved; then check every 3 mo; if cysteamine is poorly tolerated initially because of GI tract symptoms or transient rashes, temporarily stop therapy; restart at lower dose and gradually increase to proper dose. Dose is expressed as free base of drug.
Available as 50-mg and 150-mg cap.
Adult
Maintenance dose (>50 kg): 500 mg/dose PO q6h
Administer one fourth to one sixth of maintenance dose initially; then increase gradually over 4-6 wk to avoid intolerance and achieve a leukocyte cystine level <1.0 nmol half-cystine/mg protein
Pediatric
Maintenance dose:
<12 years: 1.3-1.95 g/m2/d (about 60–90 mg/kg/d) PO divided q6h
May sprinkle cysteamine cap contents over food
>12 years and >50 kg: Administer as in adults
None reported; can be administered with electrolyte and mineral and vitamin D and thyroid hormone replacements necessary for management
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause occasional reversible leukopenia (reduces by almost 80%), monitor blood counts and perform liver function studies; because of adverse GI effects (eg, nausea, vomiting, duodenal ulcer), therapy may have to be interrupted and the dose adjusted; may cause CNS symptoms (eg, seizures, lethargy, somnolence, depression, encephalopathy); may also cause abnormal liver function values (monitor liver function) and rash; because of offensive smell and taste, some patients are unable to tolerate cysteamine treatment
More on Cystinosis |
| Overview: Cystinosis |
| Differential Diagnoses & Workup: Cystinosis |
 Treatment & Medication: Cystinosis |
| Follow-up: Cystinosis |
| Multimedia: Cystinosis |
| References |
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References
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Further Reading
Keywords
cystinosis, cystine storage disease, Fanconi syndrome, infantile cystinosis, infantile nephropathic cystinosis, adolescent cystinosis, adult cystinosis, ocular cystinosis, end-stage kidney failure, cysteine, metabolic acidosis, electrolyte disturbances, renal transplantation, ocular cystinosis, polyuria, polydipsia, dehydration, normal anion gap hyperchloremic acidosis, hypophosphatemic rickets, failure to thrive, severe photophobia, corneal ulcerations, retinal blindness, delayed puberty, hypothyroidism, pancreatic disease, exocrine insufficiency, insulin-dependent diabetes mellitus, hepatosplenomegaly, nodular degenerative hyperplasia, distal vacuolar myopathy, calcifications, atrophy, pseudotumor cerebri, polydipsia, polyuria, renal tubular abnormalities
