IntroductionThe number of persons receiving renal replacement therapy (RRT) is estimated at more than 2.5 million worldwide, and is growing by 8% annually. Registries in the developing world are not up to standards compared to the United States Renal Data System (USRDS). Herein we examine the causes, progression, and magnitude of end-stage kidney disease (ESKD) over 3 decades in Oman.MethodsWe examined ESKD data from 1983 to 2013. Data from 1998 to 2013 were obtained through an Information Management System. Data before 2008 were collected from patients’ files. A questionnaire based on USRDS form 2728 was completed by nephrologists once a citizen reached ESKD.ResultsA total of 4066 forms were completed, with a response rate of 90% (52% male). The mean (SD) age was 50.1 (14.0) years. By 31 December 2013, there were 2386 patients alive on RRT, of whom 1206 were on hemodialysis (50.5%), 1080 were living with a functioning kidney transplant (45.3%), and 100 were receiving peritoneal dialysis (4.2%). The incidence of ESKD on RRT was 21, 75, and 120 per million population in 1983, 2001, and 2013, respectively. Similarly, the prevalence of ESKD was 49, 916, and 2386 in 1983, 2001, and 2013 respectively. Among patients with ESKD on RRT, a progressive rise was seen in diabetic nephropathy, with 5.8%, 32.1%, and 46% in 1983, 2001, and 2013 respectively.DiscussionThe incidence and prevalence of ESKD has increased progressively over last 30 years. This is anticipated to continue at an even higher rate in view of the progressive rise in noncommunicable diseases. Continuous improvement in registries is required to improve capturing of ESKD patients for providing accurate data to health authorities, and enhancing public awareness of the magnitude, future trends, treatments, and outcomes regarding ESKD.

Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

This is the largest single-center study on commercial RTX reporting the highest number of patients with IFI acquired over a relatively short period of time. Aspergillus spp were the main culprit fungi, with no Candida spp being isolated. A high index of suspicion might be the most reasonable means to reduce the possible very poor outcomes. Improving legal transplant programs and strengthening the associated laws could prevent commercial transplant tourism.

Introduction: Hereditary podocytopathies are genetically highly heterogeneous. Extra-renal symptoms, when associated, are specific for the causal gene. Two unrelated pedigrees presented with a novel infantileonset severe disorder characterized by steroid-resistant nephrotic syndrome (SRNS), cataracts, sensorineural deafness and enterocolitis. In the first four-generation pedigree (FamA), the disorder segregated in an X-linked pattern and in an autosomal recessive mode in the second (FamB). Since the disorder did not correspond to any of the known podocytopathies, we aimed to identify the causal genes. Methods: We performed linkage analysis and multiple parallel sequencing to identify the causal mutations. Flow cytometry, Southern blot and MM-qPCR to measure telomere length. X-inactivation was assessed by qPCR. Molecular dynamics simulations, co-immunoprecipitation and pressure tuning fluorescence spectroscopy were used to assess the complex formation capacity of the mutant proteins. Zebrafish dkc1 mutants were generated using CRISPR/Cas9. Pseudouridylation was assessed In patients and zebrafish by immuno-Northern and HPLC-MS. Whole transcriptome analysis was performed in zebrafish mutants. The localisation of the mutant protein was determined by immunocytochemistry. Results: Linkage analysis in Family A idenified a 5 Mb region in Xq28 and a homozygous region of 2.6Mb in 15q14 in FamB. We found a DKC1 mutation (c.616 G>A, p.Glu206Lys) in FamA which appeared de novo in the second generation in parallel with the disorder and a homozygous NOP10 mutation (c.47C>T, p.Thr16Met) in FamB. Both mutations affected evolutionary conserved amino acids, were predicted to be pathogenic and were absent from population databases. The affected proteins, dyskerin and NOP10, are core members of the H/ACA snoRNP complexes, implicated in the pseudouridylation of RNAs and in telomere maintenance. Based on molecular dynamics simulations, the two affected amino acids interact with each other in the wild type H/ACA snoRNP complex. We found both of their mutations to impair the dyskerin-NOP10 interaction as reflected in an altered dissociation constant and to also disrupt the pseudouridylation catalytic site. We found both telomere attrition and a pseudouridylation defect in the patients. Despite telomere attrition, no mucocutaneous features were suggestive of dyskeratosis congenita. Zebrafish dkc1 null mutants recapitulated the human phenotype, which was rescued by the wild type, but not by the p.Glu206Lys human dyskerin. Mutant larvae showed reduced 18S pseudouridylation and low amount of 18S rRNA, but no telomere attrition. Transcriptomic analysis of the mutant larvae also suggested ribosome biogenesis defect. We found wild type embryos to develop a similar phenotype after cycloheximide treatment. Conclusions: We described a novel SRNS phenotype secondary to DKC1 and NOP10 mutations and propose that it represents the consequences of defective pseudouridylation and ribosomal dysfunction.Introduction: The systemic lupus erythematosus (SLE)...

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