Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study

Veys, Koenraad; Zadora, Ward; Hohenfellner, Katharina; Böckenhauer, Detlef; Janssen, Mirian C. H.; Niaudet, Patrick; Topaloğlu, Rezan; Besouw, Martine; Novo, Robert; Haffner, Dieter; Kanzelmeyer, Nele; Pape, Lars; Wühl, Elke; Harms, Erik; Awan, Atif; Sikora, Przemysław; Ariceta, Gema; Heuvel, Bert van den; Levtchenko, Elena

doi:10.1002/jimd.12562

Cited by 9 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, neonatal screening is now considered one of the most efficient strategies to identify the disease and initiate treatment as early as possible, which could delay the onset of kidney failure and provide optimized care for NC patients. A recent study from Germany showed that starting cysteamine soon after birth yielded almost normal growth and kidney function in these patients with a neonatal diagnosis [ 30 , 31 ]. Still, the availability of such strategies in low-income countries is questionable, let alone access to potential innovative therapies such as stem cell transplantation [ 32 ], or inflammation-targeted therapies [ 33 ], which are very likely to be available only in a restricted number of DEed countries.…”

Section: Discussionmentioning

confidence: 99%

Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective

Regnier,

Flammier,

Boutaba

et al. 2023

Pediatr Nephrol

Self Cite

View full text Add to dashboard Cite

Background Nephropathic cystinosis (NC) is a rare lysosomal disease, leading to early kidney failure and extra-renal comorbidities. Its prognosis strongly relies on early diagnosis and treatment by cysteamine. Developing economies (DEing) face many challenges when treating patients for rare and chronic diseases. The aim here is to evaluate the access to investigations and treatment in DEing, and to assess for potential inequalities with Developed Economies (DEed). Methods In this international cross-sectional study, a questionnaire on access, price and reimbursement of genetic, biological analyses, and treatment was sent to nephrology centers worldwide during 2022. Results A total of 109 centers responded, coming from 49 countries and managing 741 patients: 43 centers from 30 DEing and Economies in transition (TrE), and 66 from 19 DEed. In 2022, genetics availability was 63% in DEing and 100% in DEed, whereas intra leukocytes cystine levels (IL-CL) were available for 30% of DEing patients, and 94% of DEed patients, both increasing over the last decade, as has access to immediate release cysteamine and to cysteamine eye drops in DEing. However, delayed released cysteamine can be delivered to only 7% vs. 74% of patients from DEing and DEed, respectively, and is still poorly reimbursed in DEing. Conclusions Over the last decade, access to investigations (namely genetics and IL-CL) and to cysteamine have improved in DEing and TrE. However, discrepancies remain with DEed: access to delayed released cysteamine is limited, and reimbursement is still profoundly insufficient, therefore limiting their current use. Graphical abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective

Regnier,

Flammier,

Boutaba

et al. 2023

Pediatr Nephrol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, this analysis considers patients diagnosed from birth and initiating treatment shortly thereafter (i.e., before the age of 5). However, there is evidence to show an independent and significant positive relationship between age at treatment initiation and kidney and overall survival [ 8 , 17 , 24 ]. Therefore, this analysis could be extended such that results are stratified not only by compliance levels but also by age at treatment initiation.…”

Section: Discussionmentioning

confidence: 99%

“…For example, considering the top 10% of CCSs (i.e., the most compliant patients) assessed in Nesterova et al (2015), the mean age-at-KF observed was approximately 23 years [ 13 ]. Although Nesterova et al (2015) do not make explicit the age at treatment initiation for these patients, it is likely these patients started treatment early; recent data from Emma et al (2021) make clear that age at renal failure (defined as stage 5 chronic kidney disease) is significantly associated with age at treatment initiation [ 17 , 24 ]. Furthermore, Emma et al (2021) also shows a median age of approximately 18 years before renal failure for patients with a mean leucocyte cystine level between 1.2 and 1.8 nmols, irrespective of age at initiation or treatment duration [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Impact of compliance to oral cysteamine treatment on the costs of Kidney failure in patients with nephropathic cystinosis in the United Kingdom

Lashilola,

Xu,

Azimpour

et al. 2023

BMC Nephrol

View full text Add to dashboard Cite

Background Nephropathic Cystinosis (NC), a rare disease characterised by intra-lysosomal accumulation of cystine, results in progressive kidney failure (KF). Compliance to lifelong oral cysteamine, the only therapy, is often compromised. The relationship between compliance and costs of NC has not been previously formally assessed. The present study evaluates the impact of compliance on lifetime (direct) costs of treating KF in NC patients in the United Kingdom. Methods A three-state (KF-free, post-KF, death) partitioned survival model was developed for hypothetical ‘Good Compliance’ (GC) and ‘Poor Compliance’ (PC) cohorts. Survival in the KF-free state was determined by a published regression function of composite compliance score (CCS). The CCS is a summation of annual compliance scores (ACS) over treatment duration prior to KF. ACSs are indexed on annual (average) leukocyte cystine levels (LCL). The Poor Compliance cohort was defined to reflect NC patients in a previous study with a mean LCL of 2.35 nmols nmol half-cystine/mg protein over the study period – and an estimated mean ACS of 1.64 over a 13.4 year treatment duration. The Good Compliance cohort was assumed to have an ACS of 2.25 for 21 years. Major KF costs were evaluated – i.e., dialysis, kidney transplants, and subsequent monitoring. Results The mean CCS was 47 for the GC and 22 for the PC cohort respectively, corresponding to estimated lifetime KF costs of £92,370 and £117,830 respectively – i.e., a cost saving of £25,460/patient, or £1,005/patient for every 1-unit improvement in CCS. Conclusion This analysis indicates that lifetime costs of KF in NC can be reduced through improved treatment compliance with oral cysteamine.

show abstract

“…However, a strict dosing schedule and accurate therapeutic follow-up is required [ 4 ]. Cysteamine should be administered immediately upon the diagnosis of nephropathic cystinosis, as any delay in treatment negatively impacts long-term renal outcome [ 11 , 12 ]. Patients with ocular cystinosis do not require systemic cysteamine, and their treatment is limited to focal cysteamine eye drops to treat corneal cystine crystals.…”

Section: Introductionmentioning

confidence: 99%

The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis

Bondue

Kouraich

Berlingerio

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Cystinosis is an autosomal recessive lysosomal storage disease, caused by mutations in the CTNS gene, resulting in multi-organ cystine accumulation. Three forms of cystinosis are distinguished: infantile and juvenile nephropathic cystinosis affecting kidneys and other organs such as the eyes, endocrine system, muscles, and brain, and adult ocular cystinosis affecting only the eyes. Currently, elevated white blood cell (WBC) cystine content is the gold standard for the diagnosis of cystinosis. We present a patient with proteinuria at adolescent age and corneal cystine crystals, but only slightly elevated WBC cystine levels (1.31 ½ cystine/mg protein), precluding the diagnosis of nephropathic cystinosis. We demonstrate increased levels of cystine in skin fibroblasts and urine-derived kidney cells (proximal tubular epithelial cells and podocytes), that were higher than the values observed in the WBC and healthy control. CTNS gene analysis shows the presence of a homozygous missense mutation (c.590 A > G; p.Asn177Ser), previously described in the Arab population. Our observation underlines that low WBC cystine levels can be observed in patients with juvenile cystinosis, which may delay the diagnosis and timely administration of cysteamine. In such patients, the diagnosis can be confirmed by cystine measurement in slow-dividing cells and by molecular analysis of the CTNS gene.

show abstract

Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study

Cited by 9 publications

References 32 publications

Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective

Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective

Impact of compliance to oral cysteamine treatment on the costs of Kidney failure in patients with nephropathic cystinosis in the United Kingdom

The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis

Contact Info

Product

Resources

About