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A potential new method to estimate tissue cystine content in nephropathic cystinosis
Ranjan Dohil1, Alison Carrigg, Robert Newbury
1Departments of Pediatrics and Pathology, University of California, San Diego, La Jolla, CA, USA.
Insights
Intestinal mucosal cystine crystals (CC) can estimate tissue cystine in children with cystinosis. Higher CC counts correlate with kidney function and white blood cell cystine levels, aiding treatment monitoring.
Area of Science:
- Pediatric Nephrology
- Metabolic Disorders
- Gastroenterology
Background:
- Cystinosis is a rare genetic disorder characterized by lysosomal accumulation of cystine.
- Accurate assessment of cystine burden is crucial for monitoring disease progression and treatment efficacy.
- Current methods for assessing cystine levels may not fully reflect tissue accumulation.
Purpose of the Study:
- To evaluate the utility of intestinal mucosal cystine crystal (CC) load as a surrogate marker for tissue cystine content in pediatric patients with cystinosis.
- To correlate intestinal CC counts with clinical parameters including estimated glomerular filtration rate (eGFR) and white blood cell (WBC) cystine levels.
Main Methods:
- Intestinal mucosal biopsies were obtained endoscopically from children (ages 2-18 years) diagnosed with cystinosis.
- A specialized processing technique allowed for visualization and enumeration of CC within histiocytes.
- Mean CC counts from the stomach and duodenum combined (CC-GD) were correlated with cysteamine treatment duration, eGFR, and mean WBC cystine levels.
Main Results:
- Seventeen subjects were enrolled; mean CC-GD count was 12.5 ± 1.41 crystals/histiocyte.
- CC-GD counts were significantly lower than colonic crystal counts (23.6 ± 3.38, P = .0031).
- Over two years, CC-GD showed a trend toward decrease (P = .065) but biopsies remained positive for CC.
- CC-GD showed inverse correlation with eGFR (P = .026) and positive correlation with mean WBC cystine levels (P = .023).
Conclusions:
- Intestinal mucosal CC are readily visible and quantifiable using histopathology.
- CC-GD counts correlate with eGFR and WBC cystine levels, suggesting potential as a monitoring tool for cystinosis treatment.
- Persistent mucosal CC, even with low WBC cystine levels, indicate that tissue cysteamine levels may not achieve complete therapeutic efficacy.
Objectives:
To evaluate intestinal mucosal cystine crystal (CC) load as a way to estimate tissue cystine content in children with cystinosis.
Study Design:
Intestinal mucosal biopsies were obtained endoscopically from children (ages 2-18 years) with cystinosis. Using a special processing technique, CC within histiocytes were easily visible and enumerable in the mucosal tissue. Mean CC counts, calculated from stomach and duodenum combined (CC-GD), were correlated with duration of cysteamine treatment, estimated glomerular filtration rate (eGFR), and mean white blood cells (WBC) cystine levels.
Results:
Seventeen subjects (6 male) were enrolled in 2 studies from 2001 and 2003. The CC-GD count (mean 12.5 ± 1.41 crystals/histiocyte) was lower than the colonic crystal count (mean 23.6 ± 3.38, P = .0031). Nine of 17 subjects underwent repeated endoscopy 2 years later and the trend for CC-GD was to decrease over time (P = .065). Biopsies, however, were never completely depleted of CC. In subjects who were diagnosed before age 18 months, the percent change from baseline of both eGFR and CC-GD were inversely correlated (P = .026). Mean WBC cystine levels were positively correlated with CC-GD (P = .023).
Conclusions:
CC are easily visible in the intestinal mucosa. CC-GD counts appear to correlate with eGFR and may help monitor response to treatment. Even when mean WBC cystine levels are low, the mucosal CC are not depleted suggesting that tissue cysteamine levels may not achieve therapeutic efficacy.
