Epidemiology, Management, and Outcome of Atypical Hemolytic Uremic Syndrome in an Omani Cohort.

Objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease of chronic uncontrolled complement pathway activation that leads to thrombotic-microangiopathy, along with severe organ damage, including end-stage kidney disease. This study aimed to evaluate the epidemiology, management, and outcome of aHUS in an Omani population. Methods: This retrospective descriptive cohort study assessed all cases of aHUS diagnosed and followed up at two tertiary care centers in Oman from January 2008 to December 2019, based on clinical features, complement pathway assays, histopathological, and genetic testing. Results: The study accrued 19 patients who fulfilled the inclusion criteria, of whom 11 (57.9%) were male. The participants' median age was 25.0 years (range = 0.1-69.0). Most (15; 78.9%) patients presented in the acute phase of the disease. The triad of hemolytic anemia, acute kidney injury, and thrombocytopenia was present in all patients. A trigger factor (e.g., infection) was identified in 68.4% of cases. Of the 14 (73.7%) patients who underwent kidney biopsy, 10 (71.4%) were found to have aHUS in native kidneys and three in grafted kidneys. Of the 11 (57.9%) patients who underwent genetic analysis, five (45.5%) were found to have a known pathogenic variant in their aHUS susceptibility genes. Plasma exchange followed by eculizumab was the treatment method in 11 (57.9%) cases. Complete renal recovery was achieved in seven (36.8%) patients, while four (21.1%) passed away during the study period. Conclusions: The wide spectrum and multiple expressions of aHUS make it a challenge to diagnose and consequently may delay the commencement of the targeted treatment. Eculizumab is considered the first-line therapy and should be commenced as early as possible.

The Challenge of Graft Nephrectomy after Transplant Tourism.

The morbidity and mortality rates of transplant nephrectomy are closely related to the indications of nephrectomy. This study evaluates the indications, etiology, and complications of graft nephrectomies for commercial kidney transplantation (CKT). Data were analyzed retrospectively for graft nephrectomies for CKT from January 2009 to December 2017 at the Royal Hospital, Muscat, Oman. Four hundred and three patients received CKT and 34 patients required a nephrectomy. Twenty-five patients had a nephrectomy within 10 weeks of CKT in the early group, and nine patients in the late group had the graft removed later than 10 weeks. Indications for nephrectomy in the early group were acute bleeding, infarcted kidney, and pyonephrosis in 7, 11, and 7 patients, respectively; in the late group, the indications were: pain, hematuria, fever, hypertension, and infection. Overall, seven patients had major blood loss, and those patients who had a pseudoaneurysm had tissue cultures that were positive for the fungus. Postoperative complications occurred in 26 patients. There was acute bleeding in three patients from the external iliac artery at the site of the previous anastomosis, and, in all three cases, the external iliac artery was ligated. There were 12 major wound infections, and three patients died from overwhelming sepsis and disseminated intravascular coagulation. Commercial transplants carry a high risk of immunological, vascular, and infectious complications, resulting in significant morbidity and mortality.

The benefits and challenges of family genetic testing in rare genetic diseases-lessons from Fabry disease.

BACKGROUND: Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease-specific therapies when available. Fabry disease, an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non-specificity of early symptoms. Newborn screening and screening of at-risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise. METHODS: We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts' own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries. RESULTS: There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists. CONCLUSION: In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases.

Systemic Lupus Erythematosus: Symptoms and Signs at Initial Presentations.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune multisystem inflammatory condition that causes microvascular inflammation with the production of various auto-antibodies that play a major role in its pathogenesis. SLE can affect both sexes, all ages, and all ethnic groups with widespread geographical and socioeconomic backgrounds. Asia encompasses people of many sociocultural backgrounds with diverse ethnic. OBJECTIVE: Due to a lack of national epidemiological research, the incidence and prevalence of SLE in Middle Eastern and Arab countries, have only recently been studied. This article aims to explore the status of SLE in Oman and to record symptoms and signs of SLE at first presentation. METHODOLOGY: Medical records of all patients diagnosed with SLE at the Royal Hospital from 2006 to 2014 were reviewed for information recorded at first visit. SLE diagnosis was based on the American College of Rheumatology classification criteria; ACR97 (which includes the clinical manifestation and laboratory evidence). Patients with SLE disease manifestations extrapolated and analyzed. There were 966 patients diagnosed with SLE during the period from 2006 to 2014. Mean (SD) age at presentations was 35.5 (11.5) years. Majority of patients were female which constitutes 88.7% of the total SLE patients with mean age 27.6 (1.4) years. RESULTS: Constitutional symptoms were found in 48.68 of SLE population including fatigue in 35.22%, and weight changes in 13.43%. The cutaneous manifestations that were present included malar rash 37.69%, photosensitivity 35.10%, discoid lupus 17.63%, and hair loss 39.29%. Musculoskeletal manifestations were commonly seen among the studied population including arthralgia in 68.75%, myalgia in 55.65%, arthritis in 48.31%, whilst myositis, tendon abnormalities and avascular necrosis were found in only 2.47%, 0.31% and 1.98%. respectively. CONCLUSION: This is the first study of the symptoms and signs at initial clinical presentation of SLE patients compared to other studies done regionally where most have focused on clinical manifestations during the progression course of SLE. SLE manifestations may be related to the differences in the genetic make-up of the patients who come from various ethnic groups despite similar geography or sociocultural background, or to referral bias, as some studies were performed in the nephrology units and others in the rheumatology units. There is a pressing need to establish a nationwide and regional collaboration to establish LUPUS and to put forward a strategic planning with each MOH to provide an easy and efficient report of SLE cases and provide various effective management for such a debilitating syndrome.

Epidemiological Transition of End-Stage Kidney Disease in Oman.

INTRODUCTION: The 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. METHODS: We 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. RESULTS: A 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. DISCUSSION: The 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.

Epidemiology of human leukocyte antigens among omani population.

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.

Epidemiology and outcome of tuberculosis in immunocompromised patients.

The United States Renal Data System showed 1.2% and 1.6% incidences of tuberculosis (TB) in patients on peritoneal dialysis and hemodialysis (HD), respectively. Kidney transplant (KTX) patients have higher rates. We studied the epidemiology and outcome of TB in patients with kidney dysfunction in a tertiary care hospital in the past decade. We examined data of patients with TB with and without kidney dysfunction from 2006 to 2015 through an electronic system. Statistical analysis was completed using Stata software, Chicago, IL, USA. We found 581 patients with active TB of whom 37 had renal dysfunction including chronic kidney disease, HD, and KTX. No difference was found in the prevalence, age, or gender predilection. The age ranged from 1 to 95 with a mean (standard deviation) of 38.6 (21.1) years. The incidence of TB is 3 per 100,000. The number of patients per year with active TB ranges from 52 to 128 and 3 to 4 in the general population and kidney dysfunction group, respectively. Sixty-five percent of patients with kidney dysfunction had pulmonary TB, 5% had pleurisy, and 30% had extrapulmonary TB. Eighty-four percent of patients with kidney dysfunction completed the course of treatment with 16% treatment failure and 0.4% developed multidrug-resistant TB; 8% were lost to follow-up and 8% died during the treatment period. This study showed no gender predilection for TB in the general population and immunocompromised. Duration of symptoms before diagnosis of TB was shorter in kidney dysfunction patients in comparison to the general population. TB cultures were the most positive tests whereas bronchoalveolar lavage and skin test were the least positive for detecting TB in the kidney dysfunction group. Improvement in registries and screening is required to enhance the capturing rate and detection among this group, as well as providing accurate data to health authorities and the public about the magnitude, future trends, treatments, and outcomes regarding TB in kidney dysfunction.

The impact of introducing automated eGFR reporting on uncovering new cases of chronic kidney disease in a University Hospital in Saudi Arabia.

OBJECTIVE: To determine the impact of introducing eGFR automated reporting on uncovering new cases of Chronic Kidney Disease. METHODS: All serum creatinine (SCr) in adult patients attending outpatient clinics over a two-month period were recorded and eGFR estimated. Cases with a SCr within normal limits but were in CKD stage 3 (<60 mL/min) or higher were recorded and their numbers, percentages and mean ages calculated. Stages 1 and 2 were excluded from analysis because urinary albumin and other urinary abnormalities were not checked. RESULTS: A total of 26,422 SCr from different patients were included. The mean SCr was 92.5 ± 130.9 µmol/ and the mean eGFR was 99.8 ± 32.4 mL/min/1.73 m(2). Of all the10,601 males with normal SCr, 0.84% were in CKD stage 3 and in all the 14,695 female, 19.24% were in stage 2 in stage. Of all the 14,695 females with serum creatinine in the normal range, 200 (1.36%) were in CKD stage 3. The patients in stages 2 and 3 were significantly older. CONCLUSION: If our findings are shown to be true for the rest of Saudi Arabia, one could extrapolate that for each 100,000 serum creatinine assayed for males, 840 new cases will be uncovered in CKD stage 3. The corresponding number for females would be 1360 cases.