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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. [ABSTRACT FROM AUTHOR]

Background: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by kidney and extra-renal complications due to the accumulation of cystine crystals in various tissues and organs. Herein, we describe the early neuromuscular complications in a cohort of pediatric nephropathic cystinosis patients. Methods: We prospectively evaluated the clinical, biochemical, and neurophysiological data of 15 cystinosis patients. Neurophysiological evaluation was performed to confirm or exclude presence of neuropathy and/or myopathy. Results: Patients' age ranged between 20 and 216 months at time of examination. Nine patients were males. Three patients had early abnormal neurophysiological features consistent with neuromuscular involvement (clinically asymptomatic proximal myopathy with a patchy distribution in one patient and isolated asymptomatic sensory nerve conduction changes in two patients). A fourth patient had mixed abnormal motor and sensory axonal neuropathic changes associated with overt clinical features (predominantly motor symptoms). Patients with abnormal neuromuscular features were significantly older in age than the unaffected group (P = 0.005) and had a diagnosis of cystinosis with subsequent cysteamine therapy at a significantly older age than the unaffected group (P = 0.027 and 0.001, respectively). Conclusions: We expanded the recognized phenotypes of cystinosis neuromuscular complications with early proximal skeletal myopathy and symptomatic motor and sensory axonal neuropathy. Early asymptomatic neuromuscular complications could develop in pediatric patients and would require neurophysiological studies for early detection prior to development of overt clinical manifestations. Prompt diagnosis and timely initiation of cysteamine therapy with recommended dose can delay the development of neuromuscular complications. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Introduction: In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. Methods: Patients with confirmed NC, aged > 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. Results: Seventeen patients (10 girls, median age: 13.9 (5.4–33.0) years) were included. Median age at diagnosis was 17.0 (3.0–76.9) months and age at start of cysteamine was 21.0 (15.5–116.3) months. Median daily dose of cysteamine was 1.05 (0.55–1.63) g/m2/day. Over the year, the median percentage of days with a good adherence score was 80 (1–99)% decreasing to 68 (1–99)% in patients > 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1–23.9) versus 14.9 (9.2–20.5) hours for delayed release versus short acting cysteamine. Conclusion: Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract [ABSTRACT FROM AUTHOR]

Objectives: To summarize available clinical evidence for cysteamine bitartrate preparations in the treatment of nephropathic cystinosis as identified through a systematic literature review (SLR).Methods: We searched MEDLINE, MEDLINE In-Process and Embase using Ovid with a predefined search strategy through 19 January 2016. All publicly available clinical reports on the use of delayed-release (DR) cysteamine bitartrate (Procysbi 1 ) or immediate-release (IR) cysteamine bitartrate (Cystagon 2 ) in patients with cystinosis were included.Results: We identified a total of 103 publications and 10 trial records. Of these, 9 studies describe DR cysteamine bitartrate (n = 267 patients), 42 describe IR cysteamine bitartrate (n = 1,427 patients) and in 53 studies the exact preparation was not specified (n = 906 patients). The vast majority of the studies used a non-randomized study design, with randomized clinical trials (RCTs) being scarce (1 study comparing DR and IR formulation) and case reports (n = 49) being the most common study design representing 47% of the total.Conclusion: A substantial evidence base for cysteamine bitartrate in the treatment of nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality, with evidence levels of 3 or 4. [ABSTRACT FROM AUTHOR]

Background: Nephropathic cystinosis is a rare lysosomal storage disease which is characterized by the accumulation of free cystine in lysosomes and subsequent intracellular crystal formation of cystine throughout the body. If not treated with cysteamine, a cystine-depleting agent, end-stage renal disease will develop early, followed by multiple organ failure as the disease progresses. The established cysteamine formulation requires a strict dosing regimen at 6-h intervals. An extended release (ER) twice-daily formulation has recently been developed. The aim of our study was to evaluate the implementation and outcomes of this option in routine care. Methods: All pediatric cystinosis patients' records in Hannover Medical School were screened, and data on cysteamine therapy, tolerability, dosing, estimated glomerular filtration rates (eGFR), white blood cell cystine levels, and proton pump inhibitor (PPI) use were extracted for the period January 2014 to January 2016. Results: The median age of the 12 patients enrolled in the study was 12.5 (range 1-18) years. At the end of the study period ten of these patients received ER-cysteamine. There were no additional side effects. Halitosis/bad breath was often subjectively judged as improved or eliminated, and PPI use could be stopped in one of three patients. The main reasons for switching to the ER formulation were difficult night-time administration and uncontrolled disease. Mean eGFR values remained stable with a median of 67 ml/min/1.73 m before and after the transition. White blood cell (WBC) cystine values remained low after the switch (1 nmol/mg protein before and after transition; p = 0.64). Conclusions: In this single-center cohort, the switch from IR- to ER-cysteamine was safe and effective over the short term and provided advantages in terms of frequency of administration and less halitosis/bad breath. The long-term benefit of this option needs to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Background and objectives: Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal failure at ∼10 years of age. Therapy with the cystine-depleting agent cysteamine postpones renal failure, but the degree of compliance with this treatment has not been correlated with preservation of kidney function. Methods: We assessed leucocyte cystine depletion by cysteamine and created the composite compliance score that incorporates the extent of leucocyte cystine depletion, as well as duration of cysteamine treatment, into a single integer. Age at renal failure was used to gauge preservation of renal function, and the Fanconi syndrome index (FSI), a measure of aminoaciduria, was used to assess renal tubular Fanconi syndrome. Results: Age at renal failure varied directly and linearly with the composite compliance score ( y = 0.3x +8.8; R = 0.61). The slope indicated that for every year of excellent cystine depletion, nearly 1 year of renal function was preserved. Age at renal failure correlated roughly with mean leucocyte cystine level, but not with mean cysteamine dosage. There was no correlation between the FSI and the composite compliance score. Conclusions: Greater compliance with oral cysteamine therapy yields greater preservation of renal glomerular, but not tubular, function. Oral cysteamine therapy should be given at the maximum tolerated dose, within the recommended limits. [ABSTRACT FROM AUTHOR]

Nephropathic cystinosis (NC) is a severe disease that is complicated by early-onset chronic renal failure (CRF) and other complications related to cystine deposition in tissue. Since the 1980s, the prognosis of NC has dramatically improved after the introduction of cysteamine treatment. Limited data are available documenting improvement in prognosis. We reviewed our long-term data (follow-up 6.3-27.8 years) on 23 patients followed in the past 26 years. Overall, stage III CRF was reached at 10 years of age in >90% of patients, whereas >80% reached end-stage renal disease before the age of 14 years. Three patients died during the follow-up. Our analysis shows a clear improvement in renal outcome ( p = 0.001) and linear growth ( p = 0.04) in patients treated more recently. Improvement in the evolution of renal function was significantly associated with early initiation of cysteamine ( p = 0.006), with the dose of cysteamine ( p = 0.04), and with the use of angiotensin-converting enzyme inhibitors ( p = 0.01). Nonrenal long-term complications are similar to previously reported data. Of note, 3/23 patients developed rare forms of primary tumors that were successfully treated. In conclusion, our experience shows a significant improvement in the renal and nonrenal complications of cystinosis over the past decades and highlights the importance of early diagnosis in order to initiate cysteamine as soon as possible. [ABSTRACT FROM AUTHOR]