Markello T C, Bernardini I M, Gahl W A
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md. 20892.
N Engl J Med. 1993 Apr 22;328(16):1157-62. doi: 10.1056/NEJM199304223281604.
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.
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.
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.
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.
溶酶体贮积病胱氨酸病通常会在患儿10岁左右导致肾衰竭。尽管口服半胱胺疗法被认为可保留肾功能，但肾脏获益程度尚未确定。
1960年至1992年间，我们在美国国立卫生研究院对76例胱氨酸病患儿进行了1081次住院期间的24小时肌酐清除率测定。17名儿童被认为接受了足够剂量的半胱胺治疗，因为他们白细胞中的胱氨酸已消耗，且在2岁前开始治疗；治疗平均持续7.1年。32名儿童被认为接受了部分治疗，因为他们对治疗依从性差或在2岁后开始治疗；治疗平均持续4.5年。27名儿童在半胱胺治疗时代之前接受随访，因此从未接受过半胱胺治疗。
在从未接受过半胱胺治疗的27名儿童中，16名在美国国立卫生研究院接受随访直至出现肾衰竭；他们在平均年龄8.3±1.9岁时，平均（±标准差）肌酐清除率为每分钟每1.73平方米体表面积8.0±4.8毫升。在接受了足够剂量治疗的17名儿童中，无人出现肾衰竭；他们在8.3±3.8岁时，平均肌酐清除率为每分钟每1.73平方米57±20毫升。接受了部分或足够剂量半胱胺治疗的儿童，其平均肌酐清除率在5岁前随年龄增加，之后以正常速率随年龄呈线性下降。对于接受了足够剂量治疗的儿童，预计其平均肌酐清除率在74岁时降至每分钟每1.73平方米0毫升，而接受了部分治疗的儿童为20岁。未经治疗的情况下，平均肌酐清除率在10岁时降至每分钟每1.73平方米0毫升。
早期且充分接受半胱胺治疗的胱氨酸病患儿，其肾功能在生命的前五年会增加，然后以正常速率下降。依从性较差的患者以及年龄较大时才开始治疗的患者，治疗效果较差。
