Body growth, upper arm fat area, and clinical parameters in children with nephropathic cystinosis compared with other pediatric chronic kidney disease entities

Abstract

Children with infantile nephropathic cystinosis (INC), an inherited lysosomal storage disease resulting in cystine accumulation in all body cells, are prone to progressive chronic kidney disease (CKD), impaired growth and reduced weight gain; however, systematic anthropometric analyses are lacking. In this prospective multicenter study we investigated linear growth, body proportion, body mass index (BMI), upper arm fat area (UFA) and biochemical parameters in 43 pediatric INC patients with CKD stages 1 to 5 and 49 age‐matched CKD controls, with 193 annual measurements. INC patients showed more impaired height than CKD controls (−1.8 vs −0.7 z‐score; P < .001), despite adequate cysteamine therapy, treatment for Fanconi syndrome and more frequent use of growth hormone. Only the youngest INC patients shared the same body pattern with CKD controls characterized by preferential impairment of leg length and rather preserved trunk length. In late‐prepuberty, body pattern changed only in INC patients due to improved leg growth and more impaired trunk length. Mean UFA z‐score in INC patients was slightly reduced in early childhood and progressively decreased thereafter reaching −0.8 z‐score in adolescence, while CKD controls showed a steady increase in standardized BMI and UFA especially during adolescent age. Menarche in female INC patients was significantly delayed compared to CKD controls. Our data indicate that with age and progression of disease, pediatric INC patients undergo unique changes of body growth and fat stores that are distinct from those with CKD stemming from other causes, suggesting other factors apart from CKD to contribute to this development. Pediatric patients with infantile nephropathic cystinosis display more severe impaired linear growth than other peer CKD patients, despite of cysteamine treatment, supplementation for Fanconi syndrome, and more frequent use of growth hormone, with a distinct change of body proportions and overall lower body fat.

Patients With Infantile Nephropathic Cystinosis in Germany and Austria: A Retrospective Cohort Study

“…We were able to show that even though medication in Germany and Austria started at an early age, patients remained very short in stature. Our results are in concordance with another study focusing on patient's body growth before initiation of KRT ( 23 ). However, our data was not sufficient to explain the great interindividual variety, with several patients having fewer difficulties than others.…”

“…Muscle impairment is not only of concern for bone metabolism and strength, but may lead to swallowing difficulties and respiratory insufficiency ( 16 , 18 ). Short stature, skeletal pain and deformities, as well as a higher risk of fractures are more common in INC and growth also seems to follow a different pattern than in other nosologic entities of chronic kidney disease (CKD) ( 22 , 23 ). A primary defect in cystinotic osteoblasts and osteoclasts as well as secondary implications of INC account for the so-called cystinosis-associated metabolic bone disease ( 22 , 24 , 25 ).…”

Chest configuration in children and adolescents with infantile nephropathic cystinosis compared with other chronic kidney disease entities and its clinical determinants

“…Patients with cystinosis presented with substantially reduced shoulder and chest width, as well as height, but increased chest depth, resulting in a marked increase in APC-height and APC-transverse chest ratio, in z -scores (> 1) and in comparison to their peers with CKD. During early childhood, standardized APC-height ratio appeared as the most pronounced measure of chest disproportion in patients with INC, reaching its maximum at 7–12 years, and was less pronounced in adolescent age likely due to the observed parallel increase in height attributed to increased leg growth [ 10 ]. Standardized APC-transverse ratio, on the other hand, exhibited a sustained continuous increase, suggesting disproportion within the horizontal plane of the ribcage of INC patients to intensify with increasing age.…”

“…This analysis includes children with INC and hereditary or congenital CKD aged 2 to 17 years with CKD stages 1–5 only prior to kidney replacement therapy who are enrolled in the prospective multicenter observational cohort study “Growth and cognitive-motor abilities in children with nephropathic cystinosis and chronic kidney disease” [ 10 , 15 ]. Patients with complex or syndromic diseases were excluded.…”

“…Despite adequate treatment of Fanconi syndrome and cystine depleting therapy, which was shown to delay the need for kidney replacement therapy, children with INC are prone to progressive disproportionate short stature [ 10 , 11 ]. This is characterized by a shift from a trunk length preserving pattern shared with children with CKD of other causes to an INC-specific leg-focused growth pattern [ 10 ], prompting further examination of the morphology of the trunk of INC patients.…”