Bahriye Atmis1, Aysun K Bayazit2, Derya Cevizli2, Deniz Kor3, Hatice Busra Fidan4, Atil Bisgin5,6,7, Sebile Kilavuz3, Ilker Unal8, Kivilcim Eren Erdogan9, Engin Melek2, Gulfiliz Gonlusen9, Ali Anarat2, Neslihan Onenli Mungan3. 1. Department of Pediatric Nephrology, Cukurova University Faculty of Medicine, Adana, Turkey. bahriyeatmis@gmail.com. 2. Department of Pediatric Nephrology, Cukurova University Faculty of Medicine, Adana, Turkey. 3. Department of Pediatric Metabolism and Nutrition, Cukurova University Faculty of Medicine, Adana, Turkey. 4. Department of Pediatrics, Cukurova University Faculty of Medicine, Adana, Turkey. 5. Department of Medical Genetics, Cukurova University Faculty of Medicine, Adana, Turkey. 6. Cukurova University AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center), Adana, Turkey. 7. Medical Genetics Department of Balcali Clinics and Hospital, Faculty of Medicine, Adana, Turkey. 8. Department of Biostatistics, Cukurova University Faculty of Medicine, Adana, Turkey. 9. Department of Pathology, Cukurova University Faculty of Medicine, Adana, Turkey.
Abstract
BACKGROUND: Cystinosis is a lysosomal storage disease that affects many tissues. Its prognosis depends predominantly on kidney involvement. Cystinosis has three clinical forms: nephropathic infantile, nephropathic juvenile and non-nephropathic adult. Proximal tubular dysfunction is prominent in the infantile form, whereas a combination of glomerular and tubular alterations are observed in the juvenile form. METHODS: Thirty-six children with nephropathic cystinosis were included in the study. Clinical features, molecular genetic diagnoses, and kidney outcomes of the patients were evaluated. RESULTS: Twenty-one children (58.3%) were male. The median age at diagnosis was 18.5 months. Twenty-eight patients (77.8%) had infantile nephropathic cystinosis, while eight (22.2%) had juvenile nephropathic cystinosis. An acute rapid deterioration of the kidney function with proteinuria, hypoalbuminemia, and nephrotic syndrome, was observed in 37.5% of patients with the juvenile form. The mean estimated glomerular filtration rate (eGFR) was 82.31 ± 37.45 ml/min/1.73m2 at diagnosis and 63.10 ± 54.60 ml/min/1.73m2 at the last visit (p = 0.01). Six patients (16.6%) had kidney replacement therapy (KRT) at the last visit. The median age of patients with kidney failure was 122 months. Patients with a spot urine protein/creatinine ratio < 6 mg/mg at the time of diagnosis had better kidney outcomes (p = 0.01). The most common allele was c.451A>G (32.6%). The patients with the most common mutation tended to have higher mean eGFR and lower leukocyte cystine levels than patients with other mutations. CONCLUSION: Glomerulonephritis may be a frequent finding in addition to the well-known tubular dysfunction in patients with cystinosis. Furthermore, our results highlight that the presence of severe proteinuria at the time of diagnosis is a relevant prognostic factor for kidney survival.
BACKGROUND: Cystinosis is a lysosomal storage disease that affects many tissues. Its prognosis depends predominantly on kidney involvement. Cystinosis has three clinical forms: nephropathic infantile, nephropathic juvenile and non-nephropathic adult. Proximal tubular dysfunction is prominent in the infantile form, whereas a combination of glomerular and tubular alterations are observed in the juvenile form. METHODS: Thirty-six children with nephropathic cystinosis were included in the study. Clinical features, molecular genetic diagnoses, and kidney outcomes of the patients were evaluated. RESULTS: Twenty-one children (58.3%) were male. The median age at diagnosis was 18.5 months. Twenty-eight patients (77.8%) had infantile nephropathic cystinosis, while eight (22.2%) had juvenile nephropathic cystinosis. An acute rapid deterioration of the kidney function with proteinuria, hypoalbuminemia, and nephrotic syndrome, was observed in 37.5% of patients with the juvenile form. The mean estimated glomerular filtration rate (eGFR) was 82.31 ± 37.45 ml/min/1.73m2 at diagnosis and 63.10 ± 54.60 ml/min/1.73m2 at the last visit (p = 0.01). Six patients (16.6%) had kidney replacement therapy (KRT) at the last visit. The median age of patients with kidney failure was 122 months. Patients with a spot urine protein/creatinine ratio < 6 mg/mg at the time of diagnosis had better kidney outcomes (p = 0.01). The most common allele was c.451A>G (32.6%). The patients with the most common mutation tended to have higher mean eGFR and lower leukocyte cystine levels than patients with other mutations. CONCLUSION: Glomerulonephritis may be a frequent finding in addition to the well-known tubular dysfunction in patients with cystinosis. Furthermore, our results highlight that the presence of severe proteinuria at the time of diagnosis is a relevant prognostic factor for kidney survival.
Authors: Marcella Greco; Milena Brugnara; Marco Zaffanello; Anna Taranta; Anna Pastore; Francesco Emma Journal: Pediatr Nephrol Date: 2010-08-29 Impact factor: 3.714
Authors: Craig S Wong; Christopher B Pierce; Stephen R Cole; Bradley A Warady; Robert H K Mak; Nadine M Benador; Fredrick Kaskel; Susan L Furth; George J Schwartz Journal: Clin J Am Soc Nephrol Date: 2009-03-18 Impact factor: 8.237
Authors: George J Schwartz; Alvaro Muñoz; Michael F Schneider; Robert H Mak; Frederick Kaskel; Bradley A Warady; Susan L Furth Journal: J Am Soc Nephrol Date: 2009-01-21 Impact factor: 10.121
Authors: Martijn J Wilmer; Joost P Schoeber; Lambertus P van den Heuvel; Elena N Levtchenko Journal: Pediatr Nephrol Date: 2010-08-24 Impact factor: 3.714