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

Abstract

Background: Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk.

Methods: Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17 years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models.

Results: Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6 years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17 years).

Conclusion: Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Anterior–posterior chest diameter; Biacromial diameter; Chest; Chronic kidney disease; Fanconi syndrome; Infantile nephropathic cystinosis.

A higher resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

Mean z-scores of biacromial diameter (circle), anterior–posterior chest diameter (square), and transverse chest diameter (triangle) of 44 patients with infantile nephropathic cystinosis (INC) and 97 CKD controls. Data are presented for three age cohorts (2–6, 7–12, and 13–17 years) as age- and sex-dependent z-scores. Error bars represent 95% confidence intervals. Dotted lines are for illustrative purposes only, representing changes in patterns between the three observed parameters

Fig. 2

Mean z-scores of anterior–posterior chest / height ratio (APC-height ratio; circle) and anterior–posterior chest / transverse chest ratio (APC-transverse chest ratio; square), and body height (triangle) of 44 patients with infantile nephropathic cystinosis (INC) and 97 CKD controls. Data are presented for three age cohorts (2–6, 7–12, and 13–17 years) as age- and sex-dependent z-scores. Error bars represent 95% confidence intervals. Dotted lines are for illustrative purposes only, representing changes in patterns between the three observed parameters