Background and aim Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. Methods This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. Results The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. Conclusion PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort.

BackgroundNephropathic cystinosis is an inherited autosomal recessive lysosomal storage disorder characterized by the pathological accumulation and crystallization of cystine inside different cell types. WBC cystine determination forms the basis for the diagnosis and therapeutic monitoring with the cystine depleting drug (cysteamine). The chitotriosidase enzyme is a human chitinase, produced by activated macrophages. Its elevation is documented in several lysosomal storage disorders. Although, about 6% of Caucasians have enzyme deficiency due to homozygosity of 24-bp duplication mutation in the chitotriosidase gene, it is currently established as a screening marker and therapeutic monitor for Gaucher’s disease.MethodsPlasma chitotriosidase activity was measured in 45 cystinotic patients, and compared with 87 healthy controls and 54 renal disease patients with different degrees of renal failure (CKD1-5). Chitotriosidase levels were also correlated with WBC cystine in 32 treated patients. Furthermore, we incubated control human macrophages in-vitro with different concentrations of cystine crystals and monitored the response of tumor necrosis factor-alpha (TNF-α) and chitotriosidase activity. We also compared plasma chitotriosidase activity in cystinotic knocked-out (n = 10) versus wild-type mice (n = 10).ResultsPlasma chitotriosidase activity in cystinotic patients (0–3880, median 163 nmol/ml/h) was significantly elevated compared to healthy controls (0–90, median 18 nmol/ml/h) and to CKD patients (0–321, median 52 nmol/ml/h), P < 0.001 for both groups. Controls with decreased renal function had mild to moderate chitotriosidase elevations; however, their levels were significantly lower than in cystinotic patients with comparable degree of renal insufficiency. Chitotriosidase activity positively correlated with WBC cystine content for patients on cysteamine therapy (r = 0.8), P < 0.001. In culture, human control macrophages engulfed cystine crystals and released TNF-α into culture supernatant in a crystal concentration dependent manner. Chitotriosidase activity was also significantly increased in macrophage supernatant and cell-lysate. Furthermore, chitotriosidase activity was significantly higher in cystinotic knocked-out than in the wild-type mice, P = 0.003.ConclusionsThis study indicates that cystine crystals are potent activators of human macrophages and that chitotriosidase activity is a useful marker for this activation and a promising clinical biomarker and therapeutic monitor for nephropathic cystinosis.

We concluded that urinary TGF-β1 may serve as a marker of early renal injury in SCD.

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BACKGROUND: Anemia is one of the most common complications in end-stage renal disease (ESRD) patients. Hepcidin is a hormone that regulates iron homeostasis in patients with ESRD. Carnitine deficiency is commonly seen in hemodialysis (HD) patients. AIM: This study aimed to investigate the relationship between hepcidin and inflammatory and other anemia markers in children with ESRD and to evaluate the association of carnitine deficiency with anemia in these patients. SUBJECTS AND METHODS: Thirty pediatric patients with ESRD undergoing HD, and thirty healthy, age- and sex-matched children served as controls were included in the study. Serum levels hepcidin, iron status, high-sensitivity C-reactive protein, and total carnitine were measured. RESULTS: Statistically significant increases in serum levels of hepcidin (100.7 ± 0.99 ng\ml vs. 77.43 ± 0.8 ng\ml, p = 0.000), was found in HD children as compared to healthy controls. Statistically significant increase in serum levels of hs-CRP (3.94 ± 0.19 mg/l vs. 1.36 ± 0.07 mg/l, p = 0.04) was found in HD children as compared to healthy controls. However, serum levels of carnitine (29.59 ± 2.46 μmol/L vs. 36 ± 2.39 μmol/L, p = 0.000) showed statistically significant decreases in HD children as compared to healthy controls positive correlation was found between hepcidin and hs-CRP (r = 0.059, p = 0.042). Furthermore, a positive correlation was present between serum carnitine levels and serum iron levels (r = 0.651, p = 0.042). CONCLUSION: Serum hepcidin may be a more useful biomarker of functional iron deficiency in children on HD. The efficacy of carnitine treatment for children on HD with carnitine deficiency and its effect on anemia needs to be studied.

Background: Children with nephrotic syndrome (NS) may be at risk for metabolic bone disease because of biochemical derangement caused by renal disease as well as steroid therapy. Osteocalcin (OC) functions as an inhibitor of bone mineralization. We aimed to evaluate linear growth and bone turnover markers (including serum osteocalcin) in children with steroid-dependant/frequentlyrelapsing and steroid resistant NS in comparison to a matched control group.