ABSTRACT
BACKGROUND: Mutations in COQ8B (*615567) as a defect of coenzyme Q10 (CoQ10) cause steroid resistant nephrotic syndrome (SRNS). METHODS: To define the clinical course and prognosis of COQ8B nephropathy, we retrospectively assessed the genotype and phenotype in patients with COQ8B mutations from Chinese Children Genetic Kidney Disease Database. We performed the comparing study of renal outcome following CoQ10 treatment and renal transplantation between early genetic detection and delayed genetic detection group. RESULTS: We identified 20 (5.8%) patients with biallelic mutations of COQ8B screening for patients with SRNS, non-nephrotic proteinuria, or chronic kidney disease (CKD) of unknown origin. Patients with COQ8B mutations showed a largely renal-limited phenotype presenting with proteinuria and/or advanced CKD at the time of diagnosis. Renal biopsy uniformly showed focal segmental glomerulosclerosis. Proteinuria was decreased, whereas the renal function was preserved in five patients following CoQ10 administration combined with angiotensin-converting enzyme (ACE) inhibitor. The renal survival analysis disclosed a significantly better outcome in early genetic detection group than in delayed genetic detection group (Kaplan-Meier plot and log rank test, p = .037). Seven patients underwent deceased donor renal transplantation without recurrence of proteinuria or graft failure. Blood pressure showed decreased significantly during 6 to 12 months post transplantation. CONCLUSIONS: COQ8B mutations are one of the most common causes of adolescent-onset proteinuria and/or CKD of unknown etiology in the Chinese children. Early detection of COQ8B nephropathy following CoQ10 supplementation combined with ACE inhibitor could slow the progression of renal dysfunction. Renal transplantation in patients with COQ8B nephropathy showed no recurrence of proteinuria.
Subject(s)
Genetic Testing/methods , Nephrotic Syndrome/congenital , Phenotype , Protein Kinases/genetics , Adolescent , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Child , Early Diagnosis , Female , Graft Rejection/epidemiology , Humans , Kidney/metabolism , Kidney/pathology , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Male , Mutation , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/genetics , Nephrotic Syndrome/therapy , Postoperative Complications/epidemiology , Ubiquinone/analogs & derivatives , Ubiquinone/therapeutic useABSTRACT
Three polysaccharides (WZP1, WZP2, WZP3) and their Se-enriched products (SeWZP1, SeWZP2 and SeWZP3) were obtained from Pleurotus ostreatus using a simple, rapid method and HNO3-Na2SeO3 method, respectively. The molecular weight distribution profiles of all samples except SeWZP2 showed double peaks. The average molecular weights (Mw) of WZP1-3 were 48.6â¯kDa, 20.2â¯kDa and 11.8â¯kDa, respectively, and of SeWZP1-3 were 19.6â¯kDa, 37.7â¯kDa, 14.5â¯kDa, respectively. The complexity of monosaccharide composition of WZP1-3 was inversely proportional to the ethanol concentration used in the ethanol precipitation process. Additionally, the results of biological activity tests indicated that α-glucosidase inhibitory activity of WZP1-3 was related to the molecular weight and the monosaccharide composition complexity. The selenized modification can improve the α-glucosidase-inhibiting, hydroxyl radical-scavenging activity of P. ostreatus polysaccharides. Therefore, by improving their bioactivities by selenization, the polysaccharides of P. ostreatus could be utilized as a natural health food supplement.