Thematic Area: Nephropathic Cystinosis
The following guidance documents have been endorsed by the Workgroup following standardized quality evaluation:
J Inherit Metab Dis. 2019;42:1019–1029.
Controversies and research agenda in nephropathic cystinosis: Conclusions from a KDIGO Controversies Conference
Kidney Int 2016; 89:1192-1203
- Genetic analysis of the CTNS is recommended to con?rm each new diagnosis and is particularly critical for genetic counseling.
- Cysteamine therapy should be initiated as soon as the diagnosis is established.
- Samples should be obtained at the time of trough cysteamine, i.e. 6 hours post-dosing for immediate-release, and 12 hours post-dosing for delayed-release cysteamine bitartrate.
- Management of children should include treatment of Fanconi syndrome with electrolytes and minerals, treatment of polyuria, treatment of growth failure, treatment of the eye disorders and treatment of neurological issues.
- While the original recommended dose for cystine-reduction therapy with immediate release cysteamine compounds was 2g/day for patients >12 years or weighing >50kg, the authors propose dosing based on body surface area in adults with a maximum dose of 1.95g/m2/day.
Comments by Evaluators:
- Not an actual guideline, rather a description of current practice and description of research needs
Nephropathic cystinosis: An international consensus document
Nephrol Dial Transplant 2014; 29: iv87-iv94
- The diagnosis of cystinosis can be confirmed by
(i) measurement of leukocyte cystine levels;
(ii) demonstration of corneal cystine crystals by the slit lamp exam;
(iii) genetic analysis of the CTNS gene.
- Non-specific, symptomatic treatment of the renal Fanconi syndrome includes providing appropriate nutrition and substituting renal losses.
Indomethacin is used orally at a dose of 1–3 mg/kg/day
- When cysteamine, adequate nutrition and other symptomatic therapies fail to prevent growth retardation, treatment with recombinant human growth hormone (GH) should be considered, even in the absence of renal insufficiency.
- Current data indicates that early initiation of cysteamine delays the age of end-stage renal failure and extrarenal complications of the disease. The best effects of cysteamine on renal function are obtained if the drug is started at very young ages.
- Cysteamine should be started at a low dose due to poor gastrointestinal tolerance, and increased progressively, over 4–6 weeks, to reach a target dose of 1.30 g/m2/day of free base (for patients up to 12 years) and 2 g/day for patients older than 12 years or weighing> 50 kg.The maximum dose should not exceed 1.95 g/m2/day.
- Leucocyte cysteine level is traditionally used as a biomarker to monitor the effectiveness of cystine depletion, despite lacking demonstration of the efficacy of this approach at the tissue level.
Depending on local reference values, the dose of cysteamine is prescribed to keep trough levels below <1 nmol ½cystine/mg protein.
- Patients need to be treated topically with cysteamine hydrochloride eye drops.
Comments by Evaluators:
- Description of guideline development process lacking.