Persistent Abnormalities of Fatty Acids Profile in Children With Idiopathic Nephrotic Syndrome in Stable Remission

Steroid-sensitive nephrotic syndrome is an immunological disorder mediated by still poorly defined circulating factor(s) that target the podocyte and damage the filtration barrier. Fatty acids (FA) have several biological roles and, in particular, are strictly involved in cell to cell communication, inflammatory processes and regulation of lymphocyte pools. Studies of FAs during INS have been mainly focused on biochemical changes during the phase of proteinuria; while no information is available about FA profile in patients with idiopathic nephrotic syndrome (INS) on stable remission. Aim of this study is to assess differences in blood FA profile between pediatric patients with INS during the phase of stable remission. Blood fatty acid profile of 47 pediatric patients on stable remission and 47 matched healthy controls were evaluated with gas chromatography. Patients with INS on stable remission had significantly higher levels of PUFA and omega-6 than controls (40.17 vs. 37.91% and 36.95 vs. 34.79%), lower levels of SFA and MUFA. Considering the single fatty acids, levels of omega-6 18:2n6 linoleic acid and omega-6 20:4n6 arachidonic acid were significantly higher in patients with INS than in controls (23.01 vs. 21.55%, p-value 0.003 and 10.37 vs. 9.65%, p-value 0.01). Moreover, patients with INS showed lower levels of SFA 14:0 (0.74 vs. 0.92%) and 18:0 (10.74 vs. 11.74%) and MUFA 18:1n9 oleic acid (18.50 vs. 19.83%). To the best of our knowledge this is the first study assessing FAs profile in children with INS in stable remission. In a population of 47 patients, we were able to demonstrate a higher blood level of linoleic and arachidonic acid, and consequently of omega-6 and PUFA, compared to controls. Persistently higher than normal levels of either linoleic or arachidonic acid, could be viewed as candidate biomarker for a state of risk of relapse in children with idiopathic nephrotic syndrome

Mapping of Human Autoantibody Binding Sites on the Calcium-Sensing Receptor

Previously, we have demonstrated the presence of anti-calcium-sensing receptor (CaSR) antibodies in patients with autoimmune polyglandular syndrome type 1 (APS1), a disease that is characterized in part by hypoparathyroidism involving hypocalcemia, hyperphosphatemia, and low serum levels of parathyroid hormone. The aim of this study was to define the binding domains on the CaSR of anti-CaSR antibodies found in APS1 patients and in one patient suspected of having autoimmune hypocalciuric hypercalcemia (AHH). A phage-display library of CaSR peptides was constructed and used in biopanning experiments with patient sera. Selectively enriched IgG-binding peptides were identified by DNA sequencing, and subsequently, immunoreactivity to these peptides was confirmed in ELISA. Anti-CaSR antibody binding sites were mapped to amino acid residues 41–69, 114–126, and 171–195 at the N-terminal of the extracellular domain of the receptor. The major autoepitope was localized in the 41–69 amino acid sequence of the CaSR with antibody reactivity demonstrated in 12 of 12 (100%) APS1 patients with anti-CaSR antibodies and in 1 AHH patient with anti-CaSR antibodies. Minor epitopes were located in the 114–126 and 171–195 amino acid domains, with antibody reactivity shown in 5 of 12 (42%) and 4 of 12 (33%) APS1 patients, respectively. The results indicate that epitopes for anti-CaSR antibodies in the AHH patient and in the APS1 patients who were studied are localized in the N-terminal of the extracellular domain of the receptor. The present work has demonstrated the successful use of phage-display technology in the discovery of CaSR-specific epitopes targeted by human anti-CaSR antibodies. © 2010 American Society for Bone and Mineral Research

Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography

Background: The risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) could be related to technical or patient-related factors. The aim of this study was to assess whether clinical variables and co-morbidities influence the risk of developing PEP. Methods: Data were retrieved from the Swedish GallRiks registry, including all ERCP procedures performed in 2006-2014 for common bile duct stones. A total of 15 800 procedures were identified and cross-checked. Univariable and multivariable logistic regression analyses were conducted with the endpoint of PEP using the following co-variables: age, sex, ASA grade, previous history of acute pancreatitis, diabetes, hyperlipidaemia, hypercalcaemia, kidney disease and liver cirrhosis. Results: Women (odds ratio (OR) 1.33, 95 per cent c. i. 1.14 to 1. 55), patients aged less than 65 years (OR 1. 68, 1. 45 to 1. 94), patients with hyperlipidaemia (OR 1. 32, 1. 02 to 1. 70) and those with a previous history of acute pancreatitis (OR 5. 44, 4. 68 to 6. 31) had a significantly increased risk of PEP. In a subgroup analysis of patients with a previous history of acute pancreatitis, the mean time from previous pancreatitis to ERCP 4423 days in patients who developed PEP vs 6990 days in patients who did not (P = 0. 037). However, when the previous episode of pancreatitis had occurred more than 30 days before ERCP, this association was no longer significant (P = 0. 858). Patients with diabetes had a decreased risk of PEP (OR 0. 64, 0. 48 to 0. 85). Conclusion: Age, sex, hyperlipidaemia and previous history of recent acute pancreatitis increase the risk of PEP. The reduced risk of PEP in patients with diabetes should be explored in future studies

Renal phosphate handling in Gitelman syndrome : the results of a case–control study

BACKGROUND: Patients with Gitelman syndrome, a hereditary salt-wasting tubulopathy, have loss-of-function mutations in the SLC12A3 gene coding for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. Since the bulk of filtered phosphate is reabsorbed in the proximal tubule, renal phosphate wasting is considered exceptional in Gitelman syndrome. METHODS:We investigated the renal handling of inorganic phosphate in 12 unselected Italian patients affected with Gitelman syndrome (5 females and 7 males, aged 6.0-18 years, median age 12 years) and in 12 healthy subjects matched for gender and age (controls). The diagnosis of Gitelman syndrome among the patients had been made clinically and confirmed by molecular biology studies. RESULTS: The biochemical hallmarks of Gitelman syndrome, namely hypochloremia, hypokalemia, hypomagnesemia, increased urinary excretion of sodium, chloride, potassium and magnesium and reduced urinary excretion of calcium, were present in the 12 patients. In addition, both the plasma inorganic phosphate concentration (median and interquartile range: 1.28 [1.12-1.36] vs. 1.61 [1.51-1.66)] mmol/L) and the maximal tubular reabsorption of inorganic phosphate (1.08 [0.99-1.22] vs. 1.41 [1.38-1.47] mmol/L) were significantly lower (P\u2009<\u20090.001) in Gitelman patients than in control subjects. Circulating levels of 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin were similar in patients and controls. CONCLUSIONS: The results of our case-control study disclose a hitherto unrecognized tendency towards renal phosphate wasting with mild to moderate hypophosphatemia in Gitelman syndrome