Investigating the relationship between the number and activity of natural killer cells with increased cytomegalovirus and CMV disease after kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections caused by the cytomegalovirus are one of the most common problems in patients after kidney transplant. We examined the association of the relationship between the number and activity of natural killer cells with increased cytomegalovirus and its related disease after kidney transplantation. MATERIAL AND METHODS: In this analytical study, 58 new transplant patients in the Labbafinejad Hospital, who did not have any evidence of CMV infection, were evaluated based on the number and percentage of CD56+/16+, CD56+/16-, and CD69+ Natural Killer (NK) cells. RESULTS: The results of this study showed that CD16+ and CD56+ cells in the group of CMV Ag-positive patients are less than negative patients (p = 0.003) and the difference between the two groups are significant (p = 0.01). However, CD69+ cells did not differ significantly between the two groups (p = 0.1). Moreover, the absolute number of CD16+ and CD56+ cells declined significantly after infection with CMV unlike the CMV Ag - group(p = 0.003). DISCUSSION: These results indicate that kidney transplant patients suffering from CMV infection after transplantation have a significantly reduced total number of NK cells. On the other hand, a slight decrease in the number of NK subgroups was observed with an increase in the peak serum levels of cyclosporine. As a consequence of these findings, it can be assumed that more dosage and a higher level of the drug will result in more severe immunosuppression and, consequently, increased susceptibility to CMV infections. Thus, taking the right dose of the drug would prevent viral infections and immune system from over-activation.

Measured GFR in Donor Selection, to Do or Not to Do? That is the Question.

INTRODUCTION: The accurate assessment of the pre-donation glomerular filtration rate (GFR) is a crucial step in donor selection. We conducted a prospective cross-sectional study to identify the best equation to estimate GFR and the necessity of a radio-nuclear scan in GFR evaluation. METHODS: In this study, 154 potential donors were enrolled, and GFR equations (the MDRD study, the CKD-EPI study, and the full age spectrum [FAS]), and creatinine clearance were compared with measured GFR (mGFR) by the radio-nuclear method. RESULTS: The study results indicate that Potential donors had an mGFR of 95.56 ± 15.57 mL/min per 1.73 m2. Though body surface area (BSA) adjusted full age spectrum (FAS) and CKD-EPI equations were most correlated with mGFR, the correlation coefficients were weak (ICC: 0.3 and 0.32, respectively). Misclassification at the cut-off of 80 cc/min/ 1.73 m2 was about 42% for both equations. Besides, 16.8% of donors with eGFR more than 80 cc/min/ 1.73 m2 had a difference in split renal function, and 57.1% of participants had a > 2% probability of having an mGFR < 90 mL/min per 1.73 m2. CONCLUSION: If the nuclear scan is easily available, we suggest measuring GFR by 99mTc -DTPA scan as the preferred method. Otherwise, our data suggest utilizing mGFR in patients with high body mass index, size asymmetry in CT-scan, eGFR less than 90 mL/min per 1.73 m2 with FAS and/or CKD-EPI equation as these factors deviated the estimated GFR, and also in those with inaccurate creatinine clearance measurements or with posttest probability of having mGFR less than 90 mL/min per 1.73 m2 more than 2%.  DOI: 10.52547/ijkd.7271.

Clinical outcomes of kidney recipients with COVID-19 (COVID-19 in kidney recipients).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality since late 2019. Patients undergoing kidney transplantation (KT) are prone to COVID-19 due to immunosuppressive drug use and various comorbidities such as hypertension and diabetes. METHODS: One hundred thirty-three KT recipients with COVID-19 were included in this retrospective cohort study. Hospital mortality was considered a primary outcome, while acute kidney injury (AKI) was considered a secondary outcome. Demographic information, maintenance immunosuppression, medical history, laboratory information, and echocardiographic and electrocardiography results of patients were recorded. Patients were also followed for 2 months post-discharge for post-COVID-19 symptoms, readmission, and transplant function. RESULTS: Regarding the primary outcome of the 133 patients, 13 died and 120 survived. The deceased patients were significantly older (median age, 64 vs. 50.5 years; p = 0.04) and had a significantly higher median serum creatinine level (p = 0.002) and lower median glomerular filtration rate (p = 0.010) than patients who survived. The incidence of AKI was 47.3%, more common in deceased patients (p = 0.038) than in patients who survived. Troponin levels were significantly higher in deceased patients and those with AKI (p = 0.0004 and p = 0.039, respectively) than in patients who survived and those without AKI. A multivariable Cox regression analysis revealed that older age (adjusted hazard ratio, 1.13; 95% confidence interval, 1.01-1.27) and AKI (adjusted hazard ratio, 3.43; 95% confidence interval, 1.34-8.79) were associated with in-hospital mortality. CONCLUSION: In conclusion, kidney recipients with COVID-19 had a higher mortality rate than the general population, with a higher prevalence in older individuals and those who experienced AKI during hospitalization than in patients who survived and those without AKI.

The relationship between CT value and clinical outcomes in renal patients with COVID-19.

PURPOSE: Concomitant kidney diseases raise the mortality rate due to the SARS-CoV-2 virus as an independent factor. Although a qualitative PCR test's result is sufficient for diagnosis, Cycle threshold value may present relevant information to the physicians in providing faster treatment in patients with chronic conditions, including kidney diseases, to prevent morbidity and subsequent mortality. Thus, the present study was conducted to determine the relationship between the Cycle threshold value and clinical outcomes in renal patients with the coronavirus 2019. METHODS: This retrospective study was conducted on renal patients with the coronavirus 2019 infection admitted to Labbafinejad Hospital in Tehran, the capital of Iran, within a period of one year, from late February 2020 to February 2021. Data were collected per the prepared checklist. Cycle threshold values were measured by performing PCR on nasopharynx and oropharynx swab samples of patients. RESULTS: According to the adjusted analysis, having high viral load increased the odds of in-hospital mortality (aOR = 11.65, 95% CI 3.93-34.54), ICU admission (aOR = 5.49, 95% CI 2.16-13.97), and invasive ventilation (aOR = 7.18, 95% CI 2.61-19.74). Having high viral load also increased the odds of O2 therapy (aOR = 3.08, 95% CI 0.79-12.01), although the difference was not statistically significant (P = 0.105). CONCLUSION: Cycle threshold value was a significant predictor of mortality in renal patients. Nevertheless, further studies are required on how to render optimal use of the Cycle threshold value, given that the quality of the test sample and the different groups of patients under study affect the effectiveness of this marker in predicting disease severity.

Immunogenicity and Safety of SpikoGen, an Adjuvanted Recombinant SARS-CoV-2 Spike Protein, as a Heterologous Third Booster Dose in Kidney Transplant Patients: A Single-arm Clinical Trial.

PURPOSE: Studies have found that immunocompromised patients have suboptimal responses to COVID-19 vaccines, leading to approval of a need for booster doses in this population. SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2™ adjuvant to protect against COVID-19. Previous clinical trials found this vaccine to be tolerable, immunogenic, and efficacious in reducing the risk of COVID-19, including severe disease. However, the effects of this vaccine have not been assessed in immunocompromised patients. This study sought to assess the immunogenicity and safety of the SpikoGen vaccine as a third booster dose in patients undergoing kidney transplant who were receiving immunosuppressive therapy and had received their primary vaccination based on an inactivated whole virus platform (Sinopharm). METHODS: This single-arm trial was performed with 43 patients undergoing kidney transplant. The participants received a single booster dose of the SpikoGen vaccine 1 to 3 months after primary vaccination with 2 doses of the Sinopharm vaccine. Immunogenicity assessments were performed at baseline and 30 days after the booster dose. The primary outcomes were seroconversion rates of anti-S1 and surrogate virus neutralizing antibodies. Safety outcomes included the incidence of solicited and unsolicited adverse events in the 7 days and 1 month after the booster dose, respectively. FINDINGS: The SpikoGen vaccine induced positive humoral and cellular responses 30 days after the booster dose in those patients who were seropositive or seronegative after 2 primary doses of the Sinopharm vaccine. Thirty days after the SpikoGen vaccine booster, seroconversion rates were 35.29% (95% CI, 19.75%-53.51%) to anti-S1 and 29.41% (95% CI, 13.27%-46.57%) to surrogate neutralizing antibodies. The most common local and systemic reported solicited adverse events were injection site pain and fatigue, which were largely mild and transient. No serious adverse events were reported. IMPLICATIONS: A single booster dose of SpikoGen vaccine given 1 to 3 months after primary vaccination with 2 doses of Sinopharm vaccine induced positive humoral and cellular immune responses in immunosuppressed patients undergoing renal transplant, thereby achieving spike antibody levels predictive of protection. This study was performed as a single-center study, and it will be important for future large multicenter studies to extend these results to other immunocompromised patient groups.

Humoral immunity of BBIBP-CorV (Sinopharm) in kidney transplant recipients: Is it time to revise vaccination strategies.

BACKGROUND: The mortality of coronavirus disease 2019 (COVID-19) is high in transplant patients, and effective vaccination is aimed to reduce severe disease and mortality. METHODS: We conducted a cross-sectional study to evaluate humoral and cellular response to two 4-µg doses of BBIBP-CorV vaccine in 100 kidney transplant recipients, using anti-spike IgG, total anti-receptor-binding domain, neutralizing antibody (Ab) level (enzyme-linked immunoassay), and interferon-gamma release assay (IGRA). RESULTS: Seroconversion was evaluated 85.84 ± 30.72 days after the second dose. Note that, 58% of all and 43.05% of infection-naïve participants have developed at least one of the tested antibodies. IGRA was positive in 30.7% of tested transplant recipients. Sixty percent of the participants had either humoral or cellular responses to COVID-19. Only age was independently linked to seropositivity of any degree after vaccination (p < .05). COVID-naïve patients older than 60 years developed significantly less neutralizing Abs. (p = .011). Six patients developed mild COVID infection more than a month after the second dose of the vaccine (54.5 ± 20.8 days). No vaccine-related adverse effects were reported, except self-limited mild to moderate fever and injection site pain. CONCLUSION: BBIBP-CorV vaccine can be used safely in kidney transplant recipients, although impaired cellular and humoral immunity necessitate adjustments in vaccination strategies, like higher (8-µg doses), fourth booster dose, or boost with different platform vaccine.

Agreement between the results of tuberculin skin test and Interferon-Gamma Release Assays in renal transplant candidates.

INTRODUCTION: Identification of latent tuberculosis (TB) infection is important in kidney transplant candidates. Due to the absence of a gold standard, both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) are used to screen patients. The aim of this study was to evaluate the agreement of these two tests in patients undergoing renal transplantation. MATERIALS AND METHODS: Two hundred kidney transplant candidates at a referral center in 2014-2017 were included in this study. TST and Quantiferon-Gold (QFT-G) tests were performed for all patients before transplantation. In case of a positive result in any of the tests, patients were administered a 9-month prophylaxis treatment using isoniazid. Cohen's kappa coefficient (k) test was used to determine the agreement between the two tests. RESULTS: The mean age of patients was 40.72 ± 18.33. Nine (4.5%) patients had positive TST and 16 (8%) had positive IGRA. Concordance of the two tests was evaluated as medium (κ = 0.44 and P < 0.001). No association was found between the underlying causes of renal failure and skin test positive or IGRA. The tests showed a poor agreement among diabetics, candidates of re-transplantation, and those who were on dialysis for longer than a year (κ < 0.20). CONCLUSION: TST or IGRA can be used to screen TB in kidney transplant candidates with a moderate agreement. However, we suggest using both TST and QFT-G in diabetics, re-transplant candidates, and those on dialysis for >1 year.

Prognostic Value of Blood Pressure Responsiveness in Hemodialysis for Cardiovascular Mortality, Development of A New Predictive Equation.

INTRODUCTION: Cardiovascular disease is considered as the main cause of mortality and morbidity in HD-patients and AS is a fundamental cause. This study was conducted to investigate whether intradialytic BP changes can use as a surrogate clinical marker. METHODS: Fifty-one patients on maintenance hemodialysis, for at least 12 hours per week, were included in a prospective cohort study. Intradialytic BP was measured using validated automated device. PWV was performed to assess Augmentation Index (AIx) as marker of arterial stiffness. All measurements were repeated in alive individuals after 5 years of follow-up. Patients with 5% reduction of intradialytic BP were considered as HD-responsive and Several statistical analyses were employed based on responsiveness to HD. RESULTS: After 5-year follow-up the findings demonstrated BP response to HD was an important and independent determinant of mortality (P < .05). Augmentation index (AIx) (P < .05), heart rate (P < .05), and calcium phosphate product (P < .05) as well as log PTH (P < .05) were significantly different between two responsive and non-responsive to HD. Pearson's Correlation studies revealed a significant relationship between the BP response to HD and heart rate (r = 0.4, P < .05), LVEF (r = -0.4, P < .05) and PTH (r = -0.3, P < .05). BP response to HD and log-PTH remained significant even after age and gender adjustment (P < .05). CONCLUSION: BP-response to HD can use as a clinical and surrogate marker of AS which is significantly associated with mortality and LVEF. Arterial stiffness and intradialytic BP can predict the changes in Ejection Fraction (EF). DOI: 10.52547/ijkd.6810.

Predictive Biomarker Panel in Proliferative Lupus Nephritis- Two-Dimensional Shotgun Proteomics.

INTRODUCTION: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematous (SLE). With no specific clinical or laboratory manifestation to predict response to treatment, this study was aimed to provide a panel of predictive biomarkers of response before initiation of treatment. METHODS: Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was performed on plasma and urine samples of 11 patients with biopsy proven proliferative LN at the time of biopsy. Unsupervised principal component analysis (PCA), orthogonal projection to latent structures discriminant analysis (OPLS-DA), gene ontology annotation and protein mapping were performed on 326 proteins in plasma and 1381 proteins in urine samples. RESULTS: Samples of eight patients achieved complete remission and three reached partial remission were analyzed. The mean 24-hour protein excretion was 3259 mg/day and the mean eGFR was 87.73 cc/min. OPLS-DA analysis of plasma samples showed a clear discrimination for complete and partial remission patients. Twenty plasma proteins and ten urine proteins with the highest fold changes and AUCs were selected as candidate biomarkers (IGHV1-18, PI16, IGHD, C3, FCER2, EPS8L2, CTTN, BLVRB). This plasma and urine biomarker panel is involved in oxidative stress, acute inflammation, reduction in regulatory T cells, complement pathway consumption, and proximal tubule bicarbonate reclamation. CONCLUSION: Our suggested panel of plasma and urine biomarkers can precisely discriminate patients with possibility of complete response to treatment. It seems that the higher indices of inflammation will associate with better chance of achieving complete remission.

Prevalence, serotyping and drug susceptibility patterns of Escherichia coli isolates from kidney transplanted patients with urinary tract infections.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) are among the main pathogens in urinary tract infections (UTIs) among kidney transplant patients (KTPs). AIM: To estimate the prevalence of ESBL-producing E. coli in KTPs and to evaluate the most prevalent serotypes and antibacterial susceptibility patterns of isolated bacteria in Tehran, Iran. METHODS: A total of 60 clinical isolates of uropathogenic E. coli were collected from 3 kidney transplant centers from April to May 2019. Antimicrobial susceptibility testing was performed by the disk diffusion method as recommended by the Clinical Laboratory and Standards Institute. The serotyping of E. coli isolates was performed by the slide agglutination method. The presence of bla TEM, bla SHV, and bla CTX-M genes was evaluated by polymerase chain reaction. RESULTS: The frequency of ESBL-producing E. coli in KTPs was found to be 33.4%. All of the 60 E. coli isolates were found to be susceptible to doripenem (100%) and ertapenem (100%). High resistance rates to ampicillin (86%), cefotaxime (80%), and cefazolin (77%) were also documented. The most frequent serotypes were serotype I (50%), serotype II (15%), serotype III (25%), and serotype VI (10%). The gene most frequently found was bla TEM (55%), followed by bla CTX-M (51%) and bla SHV (41%). CONCLUSION: Molecular analysis showed that bla TEM was the most common ESBL-encoding gene. The high resistance to ß-lactams antibiotics (i.e., ampicillin, cefotaxime, and cefazolin) found in E. coli from KTPs with UTIs remains a serious clinical challenge. Further efforts to control ESBL-producing E. coli should include the careful use of all antibiotics as well as barrier precautions to reduce spread.

Biomarkers in Primary Membranous Nephropathy, A Guide to Precision Medicine.

Membranous nephropathy (MN) as one of the most common glomerulonephritis still relies on an invasive procedure of kidney biopsy for precise recognition. Over the recent past years noninvasive methods using wide range of biomarkers have been developed in order to diagnose and estimating the final prognosis of MN. Plasma, urine and tissue are readily accessible specimens for identification of these biomarkers. In order to utilize a single biomarker or a panel of them for detection of a specific entity, many factors should taking into consideration like the accuracy, precision, and validity, accompanying with being available and cost effective. This review is focused on recently developed biomarkers and their application on the diagnosis besides determining the prognosis of MN. The clinical utilities and limitations of each biomarker are discussed in details.

Low rate of COVID-19 pneumonia in kidney transplant recipients-A battle between infection and immune response?

BACKGROUND: With COVID-19 pandemic, concerns about kidney transplant recipients are rising. However, the incidence, clinical course, outcome, and predictive factors of disease severity are obscured. METHODS: We describe clinical and laboratory manifestations, radiologic findings, clinical course, and finally outcome of kidney transplant recipients with COVID-19 pneumonia. RESULTS: Of 2493 kidney transplant recipients under follow-up in our clinic, 19 cases (4 cases diagnosed based on radiologic findings) were admitted. The mean age of patients was 47.6 ± 12.4 years, and the mean time from transplantation was 115.6 ± 70.3 months. Lymphopenia and eosinopenia were 84.2% and 78.9%, respectively. Nine patients did not survive the hospital course. History of acute rejection during the past 12 months, diabetes, higher N/L ratio, lower platelet count, elevated N/L x CRP, higher levels of LDH, positive D-dimer, higher troponin, and prolonged PT were associated with mortality. Among patients with positive COVID-19 test, history of acute rejection, low platelet count, and positive D-dimer were associated with poor outcome. Treatment with cyclosporine was associated with better clinical outcome. CONCLUSIONS: Low rate of admission in transplant recipients specially in the very first years of transplantation might be due to protective effects of immunosuppressive agents against cytokine storm or modification of immunity function. We suggest evaluation of T-cell number, function, and cytokine profile as a guide to manage COVID-19 mainly in patients with higher risk of mortality.

Clinical and Radiologic Characteristics of COVID-19 in Patients With CKD.

INTRODUCTION: In this study, we aimed to evaluate the presentation and outcome of COVID-19 in patients with chronic kidney disease (CKD). METHODS: We included 43 patients with a past history of CKD and confirmed diagnosis of COVID-19. Patients were evaluated for demographic characteristics, clinical and laboratory data and findings of initial chest computed tomography (CT) and were followed until either death or discharge occurred. Then, study variables were compared based on final outcome and stage of CKD. RESULTS: Mean age ± SD of patients was 60.65 ± 14.36 years; 65.1% were male. Five of 43 patients (11.6%) died on follow-up and the rest were discharged. Disease outcome did not differ across CKD stages (P > .05). More than half of the patients (58.1%) presented with severe disease on admission. Clinical symptoms were similar to those of non-CKD individuals. Mean duration of hospitalization was higher in those who died, although not significant (16.6 ± 8.38 vs. 11 ± 6.26, P > .05). The only hematologic parameter that significantly differed between survivors and non-survivors was lactase dehydrogenase level (P < .05). Ground-glass opacification and reticular pattern were the most frequent patterns on CT and pleural effusion existed in about one-fifth of all patients. A greater lower zone score was noted in deceased patients (P < .05). CONCLUSION: Patients with CKD are vulnerable to a more severe form of COVID-19 and experience a higher mortality rate than the general population; however, higher CKD stage is not related to worse prognosis or different imaging manifestation compared with lower stage.

Adding Colchicine to the Antiretroviral Medication - Lopinavir/Ritonavir (Kaletra) in Hospitalized Patients with Non-Severe Covid-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomized Controlled Trial.

OBJECTIVES: Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients. TRIAL DESIGN: Prospective, randomized (1:1 ratio), double blind study with parallel group design. PARTICIPANTS: Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation. EXCLUSION CRITERIA: known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 (by the CKD-EPI Creatinine Equation for Glomerular Filtration Rate (GFR) which estimates GFR based on serum creatinine. ; kidney transplant recipients, using Digoxin, QTc >450 msec. Participants will be recruited from inpatients at Labbafinejad Meidcal Center , Tehran, Iran. INTERVENTION AND COMPARATOR: Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol. MAIN OUTCOMES: Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment - C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction - Percentage of patients who require supplemental Oxygen - Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients. TRIAL STATUS: Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Clinical Course, Imaging Features, and Outcomes of COVID-19 in Kidney Transplant Recipients.

Coronavirus disease 2019 (COVID-19) is a novel and highly contagious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older adults and patients with comorbidities and immunosuppressive conditions may experience severe signs and symptoms that can lead to death. This case series assesses the clinical course, imaging features, and outcomes for 12 patients with COVID-19 and a history of kidney transplantation. Patients were evaluated for symptoms, laboratory data, imaging findings, and outcomes from February 2020 to April 2020. Fever, cough, and dyspnea were the most common clinical symptoms, noted in 75% (nine/12), 75% (nine/12), and 41.7% (five/12) of the patients, respectively. Most of the patients had a normal white blood cell count, while 33.3% (four/12) had leukopenia and 8.3% (one/12) had leukocytosis. A combination of consolidation and ground glass opacity was the most predominant (75%) pattern of lung involvement on computed tomography (CT). Eight patients died of severe COVID-19 pneumonia and acute respiratory distress syndrome and four were discharged. All recovered cases had a unilateral peripheral pattern of involvement limited to only one zone on initial chest CT. It seems that CT imaging has an important role in predicting COVID-19 outcomes for solid organ transplant recipients. Future studies with long-term follow up and more cases are needed to elucidate COVID-19 diagnosis, outcome, and management strategies for these patients.

COVID-19 Rapid Guideline in Kidney Transplant Recipients.

in the reports presented about COVID-19, patients receiving kidney transplantation have not been specifically studied and based on national flowchart, this population is classified as highrisk group, thus it is necessary to be aware of the step-by-step treatment approach of these patients. Suspicious cases included patients with a history of dry cough, chills or sore throat accompanying by shortness of breath with or without fever, patients with upper/lower respiratory symptoms with radiological manifestations as single or double-sided multilobular infiltrations on CT scan or plain chest radiography, any one that has a history of close contact with a definite COVID-19 case within the last 14 days, any one with a history of presence in COVID-19 epidemic regions within the last 14 days and patient with pneumonia that despite of proper treatment has an inappropriate clinical response and clinical condition becomes more severe in an unusual way or unexpectedly.

The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial.

OBJECTIVES: The present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients. METHODS: To conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20-60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP. RESULTS: Alpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and --6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. - 0.06 ± 0.11 pg/ml; P = 0.65). CONCLUSIONS: Our results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.

A Noninvasive Urine Metabolome Panel as Potential Biomarkers for Diagnosis of T Cell-Mediated Renal Transplant Rejection.

Acute T cell-mediated rejection (TCMR) is a major complication after renal transplantation. TCMR diagnosis is very challenging and currently depends on invasive renal biopsy and nonspecific markers such as serum creatinine. A noninvasive metabolomics panel could allow early diagnosis and improved accuracy and specificity. We report, in this study, on urine metabolome changes in renal transplant recipients diagnosed with TCMR, with a view to future metabolomics-based diagnostics in transplant medicine. We performed urine metabolomic analyses in three study groups: (1) 7 kidney transplant recipients with acute TCMR, (2) 15 kidney transplant recipients without rejection but with impaired kidney function, and (3) 6 kidney transplant recipients with stable renal function, using 1H-nuclear magnetic resonance. Multivariate modeling of metabolites suggested a diagnostic panel where the diagnostic accuracy of each metabolite was calculated by receiver operating characteristic curve analysis. The impaired metabolic pathways associated with TCMR were identified by pathway analysis. In all, a panel of nine differential metabolites encompassing nicotinamide adenine dinucleotide, 1-methylnicotinamide, cholesterol sulfate, gamma-aminobutyric acid (GABA), nicotinic acid, nicotinamide adenine dinucleotide phosphate, proline, spermidine, and alpha-hydroxyhippuric acid were identified as novel potential metabolite biomarkers of TCMR. Proline, spermidine, and GABA had the highest area under the curve (>0.7) and were overrepresented in the TCMR group. Nicotinate and nicotinamide metabolism was the most important pathway in TCMR. These findings call for clinical validation in larger study samples and suggest that urinary metabolomics warrants future consideration as a noninvasive research tool for TCMR diagnostic innovation.

Downregulation of Protein Inhibitor of Activated STAT (PIAS) 1 Is Possibly Involved in the Process of Allograft Rejection.

BACKGROUND: Protein inhibitors of activated STAT (PIAS) proteins are regarded as negative regulators of cytokine-signaling and potent immunosuppressive proteins. However, their role in the process of organ transplant rejection has not been elucidated. METHODS: In the current study, we compared transcript levels of PIAS1 to 4 in the peripheral blood of renal transplant recipients who experienced transplant rejection with those having normal transplant functions. Expression of PIAS1 was significantly higher in nonrejected group compared with the rejected group among male recipients; however, differences were insignificant among female recipients. Expressions of other PIAS genes were not different between study groups. Significant pairwise correlations were found between expression levels of PIAS genes in all study subgroups. The current investigation highlights the role of PIAS1 downregulation in the evolution of graft rejection and potentiates this gene as a predictive marker for transplant fate.

Expression Levels of lncRNAs in the Patients with the Renal Transplant Rejection.

PURPOSE: Long non-coding RNAs (lncRNAs) include a vast portion of human transcripts. They exert regulatory roles in immune responses and participate in diverse biological functions. Recent studies indicated dysregulation of lncRNAs in the process of transplant rejection. In the current study, we aimed at identification of the expression of five lncRNAs (OIP5-AS1, FAS-AS1, TUG1, NEAT1 and PANDAR) in association with the process of transplant rejection. MATERIAL AND METHODS: We assessed expression of these lncRNAs in the peripheral blood of 61 kidney transplant receivers including 29 transplant rejected patients and 32 transplant non-rejected patients using real time PCR technique. RESULTS: Expression of FAS-AS1 was significantly higher in rejected group compared to non-rejected group in males, however, differences between case and control groups were insignificant among females. For other lncRNAs no significant differences were detected between two study groups. Quantile regression model showed that patients' gender was an important parameter in determination of FAS-AS1 expression (Beta=-9.46, t=-2.82, P=0.007) but not for other lncRNAs expressions. Significant pairwise correlations were detected between expression levels of lncRNAs in a disease related manner. CONCLUSION: Based on the higher expression of FAS-AS1 in patients with transplant rejection, this lncRNA might be associated with the pathogenesis of renal transplant rejection.