Morphological changes and their associations with clinical parameters in children with nephropathic cystinosis and chronic kidney disease prior to kidney replacement therapy over 25 years

Abstract

Background: Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients' clinical and morphological presentation over the past decades have not yet been thoroughly investigated.

Methods: Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016).

Results: In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z-score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z-score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients.

Conclusions: Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear.

Keywords: Body fat mass; Body mass index; Chronic kidney disease; Growth; Infantile nephropathic cystinosis; Thoracic proportions.

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

Fig. 1

Ages at diagnosis of cystinosis and initiation of cysteamine therapy in 88 INC patients (entire sample regardless of later KRT status, see methods) presented by respective birth decade (decade 1980 = 01.01.1980–31.12.1989…) with interquartile range

Fig. 2

Stature (circle), sitting height (square), and leg length (triangle) in 64 INC and 302 CKD patients, all treated conservatively. Data is presented for the measuring periods 1998–2015 and ≥ 2016 as age- and sex-dependent SDS values (z-scores). Error bars represent 95% confidence intervals

Fig. 3

Mean SDS values of anterior–posterior chest/height ratio (APC/height ratio; filled circle), anterior–posterior chest/ transversal ratio (APC/transversal ratio; filled square), sitting height index (star), body mass index (empty diamond), and upper arm fat area (empty circle) in 64 INC and 302 CKD patients, all treated conservatively. Data is presented for the measuring periods 1998–2015 and ≥ 2016 as age- and sex-dependent SDS values (z-scores). Error bars represent 95% confidence intervals

Fig. 4

Menarcheal age of 64 INC and 302 CKD patients, all treated conservatively. Data is presented for the measuring periods 1998–2015 and ≥ 2016. Error bars represent 95% confidence intervals.