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Improved renal function in children with cystinosis treated with cysteamine
T C Markello1, I M Bernardini, W A Gahl
1Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md. 20892.
Insights
Early and adequate cysteamine therapy preserves kidney function in children with cystinosis, preventing renal failure and maintaining normal creatinine clearance decline. Late or partial treatment shows less benefit.
Area of Science:
- Nephrology
- Pediatric Nephrology
- Genetics and Inherited Diseases
Background:
- Cystinosis is a lysosomal storage disease leading to kidney failure around age 10.
- Oral cysteamine therapy is known to help preserve kidney function, but its exact renal benefits require further study.
Purpose of the Study:
- To determine the extent of renal benefit from oral cysteamine therapy in children with cystinosis.
- To compare renal function outcomes in children with cystinosis receiving adequate, partial, or no cysteamine treatment.
Main Methods:
- Retrospective analysis of 24-hour creatinine clearances in 76 children with cystinosis treated between 1960 and 1992.
- Categorization of patients into three groups: adequate cysteamine treatment (early initiation, leukocyte cystine depletion), partial treatment (poor compliance or later initiation), and no cysteamine treatment.
- Longitudinal follow-up of renal function (creatinine clearance) in relation to age and treatment status.
Main Results:
- Children receiving adequate cysteamine therapy showed no renal failure, with mean creatinine clearance of 57 +/- 20 ml/min/1.73 m2 at 8.3 +/- 3.8 years.
- Children with no cysteamine treatment experienced renal failure by a mean age of 8.3 +/- 1.9 years, with mean creatinine clearance of 8.0 +/- 4.8 ml/min/1.73 m2.
- Adequate cysteamine treatment led to predicted renal clearance reaching 0 at age 74, compared to age 20 with partial treatment and age 10 with no treatment.
Conclusions:
- Early and adequate cysteamine treatment in children with cystinosis results in improved renal function that stabilizes and then declines at a normal rate.
- Delayed or inconsistent cysteamine therapy is associated with poorer renal outcomes.
- These findings underscore the critical importance of timely and consistent cysteamine administration for managing cystinosis and preserving kidney health.
Background:
The lysosomal storage disease cystinosis results in renal failure at approximately 10 years of age. Although oral cysteamine therapy is recognized to preserve kidney function, the extent of renal benefit has not been determined.
Methods:
Between 1960 and 1992, we determined 24-hour creatinine clearances in 76 children with cystinosis during 1081 admissions to the National Institutes of Health. Seventeen children were considered to have received adequate treatment with cysteamine, since they had depletion of cystine from leukocytes and began therapy before the age of 2 years; treatment lasted a mean of 7.1 years. Thirty-two children were considered to have received partial treatment, since they had poor compliance with therapy or began treatment after the age of 2; treatment lasted a mean of 4.5 years. Twenty-seven children were followed in the era before cysteamine therapy and thus never received cysteamine.
Results:
Of the 27 children who never received cysteamine, 16 were followed at the National Institutes of Health until renal failure occurred; their mean (+/- SD) creatinine clearance was 8.0 +/- 4.8 ml per minute per 1.73 m2 of body-surface area at a mean age of 8.3 +/- 1.9 years. Of the 17 children who received adequate treatment, none had renal failure; their mean creatinine clearance was 57 +/- 20 ml per minute per 1.73 m2 at 8.3 +/- 3.8 years of age. The mean creatinine clearance of the children who received partial or adequate treatment with cysteamine increased with age up to the age of five years and then declined linearly with age at a normal rate. For the children who received adequate treatment, the mean creatinine clearance was predicted to reach 0 ml per minute per 1.73 m2 at the age of 74 years, as compared with 20 years of age for the children who received partial treatment. With no therapy, the mean creatinine clearance reaches 0 ml per minute per 1.73 m2 at 10 years of age.
Conclusions:
Children with cystinosis who are treated early and adequately with cysteamine have renal function that increases during the first five years of life and then declines at a normal rate. Patients with poorer compliance and those who are treated at an older age do less well.