High detection rate for disease-causing variants in a cohort of 30 Iranian pediatric steroid resistant nephrotic syndrome cases.

Background: Steroid resistant nephrotic syndrome (SRNS) represents a significant renal disease burden in childhood and adolescence. In contrast to steroid sensitive nephrotic syndrome (SSNS), renal outcomes are significantly poorer in SRNS. Over the past decade, extensive genetic heterogeneity has become evident while disease-causing variants are still only identified in 30% of cases in previously reported studies with proportion and type of variants identified differing depending on the age of onset and ethnical background of probands. A genetic diagnosis however can have implications regarding clinical management, including kidney transplantation, extrarenal disease manifestations, and, in some cases, even causal therapy. Genetic diagnostics therefore play an important role for the clinical care of SRNS affected individuals. Methodology and results: Here, we performed NPHS2 Sanger sequencing and subsequent exome sequencing in 30 consanguineous Iranian families with a child affected by SRNS with a mean age of onset of 16 months. We identified disease-causing variants and one variant of uncertain significance in 22 families (73%), including variants in NPHS1 (30%), followed by NPHS2 (20%), WT1 (7%) as well as in NUP205, COQ6, ARHGDIA, SGPL1, and NPHP1 in single cases. Eight of these variants have not previously been reported as disease-causing, including four NPHS1 variants and one variant in NPHS2, ARHGDIA, SGPL1, and NPHP1 each. Conclusion: In line with previous studies in non-Iranian subjects, we most frequently identified disease-causing variants in NPHS1 and NPHS2. While Sanger sequencing of NPHS2 can be considered as first diagnostic step in non-congenital cases, the genetic heterogeneity underlying SRNS renders next-generation sequencing based diagnostics as the most efficient genetic screening method. In accordance with the mainly autosomal recessive inheritance pattern, diagnostic yield can be significantly higher in consanguineous than in outbred populations.

Comparison of tacrolimus and cyclosporine for immunosuppression after renal transplantation: An updated systematic review and meta-analysis.

Kidney transplantation is usually followed by immunosuppressive therapy to prevent early rejection and prolong graft survival. The calcineurin inhibitors (CNIs) represent the most commonly used agents. However, available evidence suggests the poor outcome over the long term, maybe be due to the potential nephrotoxicity associated with CNIs. Several randomized trials have compared tacrolimus (TAC) with cyclosporine, to find the optimal agent for renal transplantation; however, studies have shown conflicting results. The aim of this study was to systematically review and update the evidence for the benefits and harm of TAC versus cyclosporine as the primary immunosuppression after renal transplantation. The study was a systematic review and meta-analysis. An electronic literature search was conducted to identify appropriated trial studies. The outcomes were presented as relative risk (RR), with 95% confidence intervals (CI). Statistical analysis used was meta-analysis. Twenty-one eligible randomized controlled trials were included in this systematic review. TAC was significantly superior to cyclosporine considering the total effect size of graft loss (RR 0.089; 95% CI0.057-0.122, P <0.001), acute rejection (RR 0.638; 95% CI 0.571-0.713, P <0.001) and hypercholeste-rolemia (RR 0.634; 95% CI, 0.539-0.746, P <0.001). On the contrary, cyclosporine seemed to be significantly superior to TAC with regard to diabetes (RR 1.891; 95% CI 1.522-2.350, P <0.001). However, no significant differences between the two CNIs were found with regard to mortality, infection, and hypertension. The review indicates that TAC is significantly superior to cyclosporine regarding graft loss, acute rejection, and hypercholesterolemia, but cyclosporine seems to be significantly superior to TAC regarding diabetes. However, further large randomized trials are suggested.

Corrigendum to "Data on insulin therapy refusal among type II diabetes mellitus patients in Mashhad, Iran" [Data in Brief 18 (2018) 2047-2050].

[This corrects the article DOI: 10.1016/j.dib.2018.04.136.].

Data on insulin therapy refusal among type II diabetes mellitus patients in Mashhad, Iran.

Insulin has been considered as a therapy option of last resort in type 2 diabetes (T2DM) management. Delay in insulin therapy is common in these patients. This study collected the data on the factors associated with insulin refusal in poorly controlled T2DM patients prior to insulin therapy. The data collected from two endocrinology outpatient clinics affiliated by Islamic Azad University of Mashhad, Iran (IAUM) from January 2016 to September 2017. Study population was adults with non-insulin-using type 2 diabetes mellitus who refused insulin therapy. A 17-items researcher made questionnaire was used to obtain demographic data and information toward causes of insulin refusal. Data were analyzed using SPPS V.16 with descriptive and analytical tests such as multiple logistic regressions. The data of 110 patients with T2DM was recorded in this study. The most prevalent cause of insulin therapy refusal was reported to be painful insulin injection (78.2%) followed by this item "I'm afraid of injecting myself with a needle" (74.5%). Regression analysis revealed that education level had a significant association with the item of "Injecting insulin is painful" (P=0.033, OR=0.357). Also age (P=0.025, OR=1.076) and disease duration (P=0.024, OR=0.231) were significantly associated with the question "taking insulin makes life less flexible". Several causes have been found regarding misconceptions about insulin therapy in T2DM patients. Specialized educational interventions are recommended for initiating successful insulin therapy in these patients.

Gastrointestinal evaluation in pediatric kidney transplantation candidates.

INTRODUCTION: Our aim was to determine the frequency of peptic ulcer and Helicobacter pylori infection by gastrointestinal evaluations in pretransplantation phase in children with end-stage renal disease (ESRD). MATERIALS AND METHODS: Twenty-four children with ESRD (13 girls and 11 boys) with a mean age of 14.7 +/- 3.4 years on maintenance hemodialysis were included in this study. Upper gastrointestinal endoscopies were performed and 4 gastric, antral, and duodenal biopsy specimens were obtained for urease test and histological study. Serum gastrin levels were measured in all patients, too. A control group was chosen to compare the rate of H pylori infection between children with ESRD and healthy children. RESULTS: Gastrointestinal symptoms were present in 16 (66.7%) of 24 patients. Seventeen (70.8%) patients had abnormal upper gastrointestinal endoscopic findings. Infection with Helicobacter pylori was detected in 16 patients and 5 healthy children (66.7% versus 20.0%, P < .001). The frequency of dyspeptic symptoms was not different significantly between uremic patients with and without H pylori infection (P = .67). The same results were found regarding the upper gastrointestinal abnormalities found by endoscopy (P = .65). Oral alkalizing supplement was received by 63% of symptomatic and 80% of asymptomatic patients. Serum gastrin levels were significantly higher in infected patients than in noninfected patients with H pylori (P < .001). CONCLUSIONS: We found a significant number of patients with peptic ulcer diseases, H pylori infection, and secondary hypergastrinemia. This study showed that clinical symptoms are not a reliable predictor of gastrointestinal problems and this is more confusing in patients who received alkalizing solutions.