Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m 2. We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m 2. We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain

ABSTRACT Introduction: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. Methods: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. Results: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). Conclusion: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations.

Inherited CD59 deficiency, where neurology and genetics intertwine.

OBJECTIVES: To describe the clinical phenotype of eight children diagnosed with CD59 deficiency and their ultimate neurological outcome. METHODS: The data of our cases were extensively reviewed both clinical and ancillary tests; investigations included: neuroimaging, neurophysiological studies, and laboratory tests. RESULTS: All patients presented during early infancy with Guillain-Barre syndrome later they suffered repeated relapses leading to the diagnosis of chronic axonal neuropathy. Recurrent stroke and acute necrotizing encephalopathy were described, 2 patients in each group. One girl developed acute disseminated encephalomyelitis while one boy developed acute transverse myelitis. Overt hemolytic anemia requiring blood transfusion reported in six patients. CONCLUSION: Inherited CD59 deficiency is an autosomal recessive disorder which can have devastating neurological consequences. First line immunotherapy including intravenous immunoglobin, corticosteroids, and plasma exchange may have transient beneficial effect. Reports of targeted therapy with eculizumab might be lifesaving. Genetic counseling is crucial.

Hematologic malignancies of primary bone marrow involvement: a decade's experience in Bahrain.

INTRODUCTION: The data on the pattern of primary hematologic malignancies in Bahrain is sparse, although previously published studies suggested rising trends in their incidence. This study aimed to compare with regional and world data and identify any changing trends. METHODS: A retrospective cross-sectional chart analysis study was done on all cases of primary hematologic malignancies of bone marrow origin of Bahraini nationals presenting during the 10-year period from January 2005 to December 2014 at the sole oncology referral center in Bahrain during the study period. RESULTS: In a total of 272 cases, the primary hematologic malignancies in decreasing order of frequency with respective median ages at diagnosis were: acute myeloid leukemia (AML; 26.1%, 39 years), acute lymphoblastic leukemia (ALL; 22.8%, 9 years), multiple myeloma (MM, 16.2%, 57 years), chronic myeloid leukemia (CML, 14%, 39.5 years), myelodysplastic syndromes (MDS; 12.5%, 56 years) and chronic lymphocytic leukemia (CLL; 5.5%, 65 years). The overall crude annual incidence rate of these malignancies was 4.8/105 population. Age-specific incidence rates were found to increase dramatically with age, except for ALL, for which it peaked in the pediatric age group. The age-standardized incidence rates (ASIRs) per 105 per year were 1.47 (AML), 1.13 (MM), 0.93 (ALL), 0.85 (MDS), 0.81 (CML) and 0.44 (CLL). CONCLUSION: The pattern of primary hematologic malignancies in Bahrain shows unique features that distinguish it from trends reported in Eastern and Western world populations. Compared to previously published reports, ASIR trends decreased in CML and ALL but increased in MDS and MM.

Utility of inflammatory biomarkers in patients with COVID-19 infections: Bahrain experience.

Aim: COVID-19 pandemic continues and dearth of information remains considering the utility of various inflammatory biomarkers. We carried out the present study to delineate the roles of these biomarkers in various strata of patients with coronavirus infection. Materials & methods: A retrospective study was carried out after obtaining approval from the relevant Ethics Committee. Patients established with COVID-19 infection as shown by positive real-time quantitative PCR test were included. Details on their demographics, diagnosis, whether they received tocilizumab, and the values of the following biomarkers were obtained: IL-6, C-reactive protein (CRP), serum ferritin, D-dimer, procalcitonin, fibrinogen, lactate dehydrogenase and creatinine kinase. Receiver operating characteristic curves were plotted and correlation of biomarkers with IL-6 were estimated. Results: One-hundred and three patients were recruited. We observed that serum ferritin followed by D-dimer had better predictive accuracy in identifying patients with pneumonia compared with asymptomatic; and CRP in addition to the earlier markers had better accuracy for predicting severe illness compared with mild-moderate. Serum IL-6 levels were significantly higher in patients with severe illness admitted in intensive care unit. Significantly, higher levels of IL-6 and serum ferritin were observed in patients receiving tocilizumab. A trend of increased IL-6 levels was observed immediately following the initiation of tocilizumab therapy followed by a drop thereafter. Conclusion: We observed serum ferritin, D-dimer and CRP to accurately predict patients developing severe COVID-19 infections as well as those at risk of developing COVID pneumonia. A trend in IL-6 levels was observed in patients on tocilizumab therapy.

HLA Matching Status Among Patients Requiring Hematopoietic Stem Cell Transplant: The Need for a National and Regional Stem Cell Bank.

OBJECTIVES: Hematopoietic stem cell transplant is a strategic treatment for many malignant and nonmalignant blood diseases. Finding an HLA-matched donor is a requirement for a successful transplantation. The aim of the current study was to explore indications, demographics, and HLA patient-donor matching status among Bahraini patients requiring this transplant. MATERIALS AND METHODS: Records of 100 patients who required hematopoietic stem cell transplant at the Salmaniya Medical Complex, Ministry of Health tertiary hospital in Bahrain were retrospectively studied. Data were analyzed and compared with data from similar studies. RESULTS: For the 100 patients, 294 potential donors were HLA typed. Indications for transplant included malignant diseases (50%) and hereditary blood diseases (50%). For those in the 0- to 5-year age group, the main indication was acute lymphoblastic leukemia, whereas acute myeloid leukemia was the main indication for those who were >5 years old. Sex distribution showed that 55% of patients were males and 45% were females. With regard to age distribution, 22% of patients were less than 5 years old, 30% were 5 to 17 years old, and 48% were 18 years and older. Patient-donor HLA matching status was 50% HLA identical, 32% haploidentical, 15% more than haploidentical, and 3% less than haploidentical. The number of potential donors per patient ranged from 1 to 11 typed for each patient (average of 2.94 ± 1.86). CONCLUSIONS: The rate of finding a family member as HLA-matched donor for hematopoietic stem cell transplant in our study on Bahraini patients was higher than reports in western countries yet close to other reports from countries with almost similar family sizes. We recommend forming a national Bahrain registry in addition to a regional Eastern Mediterranean stem cell bank to increase the success rate of finding an HLA-matched donor.

Prevalence of hepatitis B e antigenemia in Bahraini hepatitis B patients: A retrospective, single-center study.

BACKGROUND AND AIM: Hepatitis B e (HBe) antigen (HBeAg) is commonly encountered among hepatitis B patients and is indicative of active infection. There is a lack of data in the literature about the prevalence of HBeAg among hepatitis B patients in Bahrain and its impact on the disease. The aims of this study were to investigate the prevalence of HBeAg among a sample of hepatitis B patients in Bahrain and to analyze their associated laboratory profile, radiological characteristics, comorbidities, and complications. METHODS: This was a retrospective record-review study conducted on patients' records at Salmaniya Medical Complex hospital in Bahrain during the period of 2011-2016. All records of hepatitis B patients who had HBeAg tests performed were included in this study. RESULTS: Of 323 patients recruited, 18.9% had positive HBeAg. The prevalence of anti-HBe antibodies and hepatitis B core immunoglobulin G (HBc IgG) differed significantly between patients with positive and negative HBeAg (P < 0.001, P = 0.026, respectively). Alanine transferase and gamma-glutamyl transferase were significantly higher among patients with positive HBeAg (P = 0.017, P = 0.016, respectively). There was no significant difference with regard to the prevalence of hepatitis C virus, human immunodeficiency virus, hepatocellular carcinoma, or liver transplantation between HBe-positive and -negative patients (P ≥ 0.05). CONCLUSION: HBeAg is prevalent among hepatitis B patients in Bahrain and is associated with a significantly different laboratory profile.

T Regulatory Cells in Rheumatoid Arthritis with Reference to Anti-Citrullinated Peptide Antibody and TNF-alpha Inhibitor Therapy.

T regulatory cells (Tregs) plays an important role in maintaining self-tolerance and preventing autoimmune diseases by inhibiting proliferation and cytokine production of self-reactive T cells. Controversy was reported regarding the frequency of CD4+CD25+ Tregs in the peripheral circulation of rheumatoid arthritis (RA) patients compared to normal controls. Also, some showed that treatment with TNF-α inhibitor restored the capacity of Tregs. This work aimed to study Tregs in the peripheral blood of RA patients versus control in addition to those on TNF-α inhibitor therapy compared to those who have not received it and to correlate with status of anti-cyclic citrullinated peptide antibody (ACPA). Two groups of RA patients were studied; one on TNF-α inhibitor therapy and the other not. Additionally, age-matched apparently healthy controls were studied. The percentage of CD4+CD25+ T cells in the total lymphocytic cell population was determined by flow cytometry analysis while ACPA concentration was measured by a second-generation peptide-based ELISA. Mean level of Tregs was significantly lower in the studied RA patients compared to the control group. Patients in early disease (0-5 years) had low mean Tregs percentage compared to patients with long duration of disease (> 10 years) (P=0.044). Patients on TNF-α blocker therapy had elevated Tregs percentage relative to patients on methotrexate (MTX) (P=0.022) and other therapies. No effect of gender or age was found on Tregs levels. In RA patients, 85.4% were ACPA seropositive and 65.9% of seropositive patients have concentration of > 100U/ml. The mean Treg percentage was significantly lower in ACPA seronegative group compared to the seropositive group (P=0.013). In conclusion, the studied RA patients have low Treg, and TNF-α blocker therapy increased its number, compared to other therapies.

Childhood Autoimmune Hepatitis in Bahrain: a Tertiary Center Experience.

BACKGROUND: Autoimmune hepatitis (AIH) in childhood has variable modes of presentation, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe acute liver disease. In AIH, the liver biopsy histopathology shows inflammation in addition to presence of serum autoimmune antibodies and increased levels of immunoglobulin G (IgG). OBJECTIVES: To investigate the situation of childhood autoimmune hepatitis in Bahrain and to compare it with other studies worldwide. METHODS: A retrospective study describing the AIH pediatric cases diagnosed during the period of Jan 2005 to Dec 2009. We report the clinical, biochemical, histopathological, and immunological findings, mainly autoimmune profile, in addition to response to treatment, of Bahraini children with autoimmune hepatitis. RESULTS: Five Bahraini children, three females and two males were diagnosed as autoimmune hepatitis during the study period. Their ages at presentation ranged from 9 to 15 (median 10.6) years. One of our patients had a fulminating type. Two had other autoimmune related conditions, namely autoimmune sclerosing cholangitis and ulcerative colitis. All were AIH type 1. Variable response to conventional immunosuppressive therapy was found, from an excellent response with good prognosis, to cirrhosis, hepatic failure and liver transplantation. CONCLUSION: Childhood AIH is a rare medical problem in Bahrain, with both sexes affected and a variable response to immunosuppressive therapy.

T-regulatory cells in chronic rejection versus stable grafts.

OBJECTIVES: Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. MATERIALS AND METHODS: The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. RESULTS: The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

Human leukocyte antigen G and renal allograft transplant.

OBJECTIVES: Studying immune tolerance induced by HLA-G in kidney allograft acceptance may help understanding of its mechanisms, hoping in the future to boaster it and decrease the immunosuppressive drugs given that are well known to have serious adverse effects. MATERIALS AND METHODS: The current study sought to evaluate soluble HLA-G in 3 groups: kidney transplanted patients with no rejection episodes, transplanted patients with biopsy-proven renal rejection, and healthy age-matched non transplanted individuals. Three groups were studied: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); healthy, age-matched, nontransplanted individuals as controls (n = 42). Soluble HLA-G level was measured in the serum by a quantitative sandwich enzyme linked immunosorbent assay. RESULTS: sHLAG level was significantly higher in the transplanted patients compared with the control. Prograf and not cyclosporine or Rapamune had positive effects on sHLAG levels. Patients with chronic rejection had a significant lower level of sHLAG compared with a graft stable group. No effect of donor type, infection or duration posttransplant, on sHLAG levels was found. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the role of sHLAG in inducing immunotolerance postkidney transplant. The findings from the current study on the chronic rejection group, supports the on-going research of having a treatment with HLA-G/or derivate, which may constitute in the future a novel efficient antigraft rejection therapy.

Immunological aspects of biopsy-proven lupus nephritis in Bahraini patients with systemic lupus erythematosus.

Lupus nephritis (LN) is a frequent and potentially serious complication of systemic lupus erythematosus (SLE) that may influence morbidity and mortality. Immunological investigations are aiding tools to the kidney biopsy findings in early diagnosis, in addition to monitoring the effect of therapy. The aim of the present study is to highlight the role of these investigations in a group of Bahraini patients and to determine whether there is any positive association between these findings and the outcome of LN. The current study is a retrospective case-control study of randomly selected 88 SLE patients, 44 with biopsy-proven LN and 44 without, acting as controls. All renal biopsies performed during the period from 1996 to 2012 were classified according to the World Health Organization classification. Immunological investigations analyzed are: Antinuclear antibodies (ANA), anti-ds DNA, anti-ENA, anti-cardiolipin antibodies (abs) and complement components C3, C4. Human leukocyte antigen (HLA) typing class II was performed on selected cases. All patients had positive ANA (100%). A significantly high frequency of anti-Smith abs among the non-LN group (43.18%) compared with the LN group (18.18%) was found (P <0.001). On the other hand, the anti-Ro/SSA abs in the non-LN group was also found at a statistically higher frequency (20.45%) compared with that in the LN group (4.54%) (P <0.01). Anti-ds-DNA abs were found to be higher in the LN group (84.09%) compared with the non-LN group (70.45%), but the difference was not statistically significant (P = 0.082). There was a positive association of ANA positivity and low C3 and or C4 in the studied group. In our study, 88.2% of the HLA typed patients had HLADR2, DR3 or both. In conclusion, in our Arabic Bahraini SLE patients, the presence of anti-Smith, anti-Ro/SSA and anti-RNP antibodies and the absence of anti-dsDNA antibodies are independent predictive markers for renal involvement. However, more prospective studies with a larger number of patients are essential to ascertain those findings.

Why does kidney allograft fail? A long-term single-center experience.

We studied the characteristics and the predictors of survival in Bahraini renal transplant recipients with an allograft that functioned for more than 10 years. Seventy-eight patients underwent renal transplantation between 1982 and 1999. Among them, 56 patients maintained functioning allografts for more than 10 years (range 10-30 years). Characteristics of the surviving patients, data on graft survival, and determinants of outcome were obtained by reviewing all medical records. The mean age at time of renal transplantation was 33.6 ± 15.3 years. The source of the graft in 42 (75%) recipients was from living related donors with a mean age of 31.4 ± 7.7 years, and it was the first graft in 48 recipients. The primary immunosuppression regimen consisted of cyclosporine (CsA) and prednisolone. Azathioprine (AZA) was given to 52 (92.9%) recipients, while four patients received steroids and AZA only. Induction therapy was administered to 30 patients in the CsA group. Acute rejection episodes occurred in eight (14.3%) patients, of whom two experienced two episodes. During the last follow-up in January 2010, the mean serum creatinine was 118.3 ± 46.5 µmol/L. A history of cancer was noted in one patient, whereas hypertension was encountered in 54% and diabetes mellitus in 20.5%. We compared the graft functioning group with the graft failure group and found that the independent determinants of long-term graft survival included time of late acute rejection episodes and histopathologic findings of chronic allograft damage, post-transplant hypertension and serum creatinine at one year. We conclude that renal transplantation even in its earliest years and despite the associated numerous complications has provided a ten-year or more of near-normal life to patients with end-stage renal disease.

A single-center experience of renal transplantation in elderly patients.

BACKGROUND: We retrospectively reviewed the results of renal transplantation in patients over 60 years of age at our center. MATERIAL/METHODS: A retrospective study was conducted of 212 Bahraini patients receiving renal transplants from January 1979 to December 2007. All medical records were reviewed for demographic data, graft function and survival. Patient and graft survival was compared for patients above and below the age of 60. RESULTS: Seventeen patients >60 years with a mean age of 64.1+/-3.6 years at the time of transplantation. Diabetic nephropathy (52%) was the most common causes of end-stage renal disease. Mean donor age was 26+/-6 years and most of them were unrelated (82%). Of the elderly patients, 4 died: 3 with a functioning graft, 1 within one year of transplantation. Cardiovascular causes (3 patients, 75%) were the most common cause of death. Causes of graft loss were death with a functioning graft (4) and chronic rejection (1). Cox's proportional-hazards regression analysis showed on univariate analysis that pre-transplant hypertension, diabetes mellitus and vascular surgery (CABG) before transplant significantly affected the dependent variable of graft loss. Multivariate analysis did not show these variables to be significant. Kaplan Meier patient survival curves showed statistically significant differences between study (>60 years) and control (18-59 years) patients (p=0.04) at 10 year. CONCLUSIONS: We conclude that Patients older than 60 yr of age can be transplanted safely and successfully, especially when they are properly screened for the presence of significant risk factors such as severe cardiovascular disease and diabetes.

Correlation of 8-isoprostane, interleukin-6 and cardiac functions with clinical score in childhood obstructive sleep apnoea.

OBJECTIVE: Adeno-tonsillar hypertrophy is the commonest cause of childhood obstructive sleep apnoea (OSA). Our aim of the study is to correlate the severity of OSA with levels of 8-isoprostane and interleukin-6 (IL-6) and with cardiac diastolic dysfunctions. METHODS: Forty children with adenoidal hypertrophy and 20 control children were recruited. The OSA clinical score was evaluated and IL-6 and 8-isoprostane were measured in exhaled breath condensate. The cardiac functions were evaluated by conventional and tissue Doppler echocardiography (TDE). RESULTS: Higher concentrations of isoprostane-8 and IL-6 were found in group with clinical score >40 (58.595 +/- 2.86 pg/mL and 38 +/- 1.77 pg/mL, respectively) than in control group (34.9 +/- 1.5 pg/mL and 7.02 +/- 0.3 pg/mL, respectively) {p < 0.0001*}. There was positive correlation between level of isoprostane-8 and IL-6 and value of clinical score {p < 0.0001*} and also with the degree of the cardiac dysfunction in those children. CONCLUSION: The severity of OSA as indicated by clinical score was positively correlated with degree of elevation of 8-Isoprostane and IL-6 in breath condensate of children with OSA and also with degree of cardiac dysfunction. Echocardiography and tissue Doppler modality are advised to examine these children.

Neonatal sepsis 1991-2001: prevalent bacterial agents and antimicrobial susceptibilities in Bahrain.

OBJECTIVES: To investigate the organisms causing neonatal sepsis and their modifications over an extended period, to assess their changing sensitivities to antibiotics and to verify whether the policy for screening pregnant women for group B streptococci (GBS) carriage is desirable in our settings. SUBJECTS AND METHODS: Medical records of all infants with positive blood culture from the Neonatal Intensive Care Unit at Salmaniya Medical Complex between 1991 and 2001 and Bahrain Defense Force Hospital between 1999 and 2001 were reviewed. RESULTS: Of the 7,978 neonates in both hospitals 335 (4.19%) had culture-proven bacteremia. Gram-positive bacteria were isolated at constant rate over the 11-year period. The main agents isolated were coagulase-negative Staphylococcus (CoNS) in 138 cases (41%), Staphylococcus aureus in 28 newborns (8%) and GBS in 26 patients (7.8%, 0.2/1,000 live births). All of them were sensitive to penicillin G, erythromycin and clindamycin. Gram-negative bacteria were declining but Escherichia coli was isolated in 35 cases (10%). Of special concern is the increasing percentage (5.7%) of Candida isolation. No clear trend toward increasing resistance was observed, although a major difference among the two institutions was evident. Klebsiella and Enterobacter spp. showed resistance to many of the antibiotics tested, thereby posing difficult therapeutic choices. CONCLUSION: Good quality specimens are essential to evaluate the role of CoNS. The increasing threat of fungal infection must be carefully tackled. Specifically tailored policies for GBS prevention must be defined according to the local epidemiology.