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.

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.

TLR-2, TLR-4 and MyD88 genes expression in renal transplant acute and chronic rejections.

BACKGROUND: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. METHODS: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR). RESULTS: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. CONCLUSION: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.

The appropriate dose of thymoglobulin induction therapy in kidney transplantation.

BACKGROUND: Thymoglobulin is used effectively as an induction agent in kidney transplantation, but there is no consensus on the optimal dose. In order to delineate the safest effective dose, an open-labeled randomized clinical trial was designed. METHODS: In this study, 90 adult kidney transplant recipients (KTR) were randomized before transplantation in three groups to receive thymoglobulin: Arm A (4.5 mg/kg in 3 days), Arm B (4.5 mg/kg single bolus dose), and Arm C (6 mg/kg in 3 days). Renal function, infections, and rate of readmissions were evaluated during the first post transplantation year. RESULTS: Ninety adult kidney recipients were enrolled (51% deceased donor). No significant statistical difference was found in acute rejection episodes or type of rejection between these groups, although patients in Arm A showed more severe histopathologic changes according to Banff 2013 criteria, in renal biopsies (P=.03). At the first month after transplantation serum Cr was lower (P=.001) and GFR was higher (P=.04) in Arm A, but there was no significant difference among the three groups at 3, 6, and 12 months post-transplant. CONCLUSION: Although all regimens showed the same efficacy regarding the rate of rejection episodes, 3-day 4.5 mg/kg Thymoglobulin had significantly fewer complications.

1 H NMR-based metabolomics study for identifying urinary biomarkers and perturbed metabolic pathways associated with severity of IgA nephropathy: a pilot study.

The severity of IgA nephropathy (IgAN), the most common primary glomerulonephritis, is judged on the basis of histologic and clinical features. A limited number of studies have considered molecular signature of IgAN for this issue, and no reliable biomarkers have been presented non-invasively for use in patient evaluations. This study aims to identify metabolite markers excreted in the urine and impaired pathways that are associated with a known marker of severity (proteinuria) to predict mild and severe stages of IgAN. Urine samples were analysed using nuclear magnetic resonance from biopsy-proven IgAN patients at mild and severe stages. Multivariate statistical analysis and pathway analysis were performed. The most changed metabolites were acetoacetate, hypotaurine, homocysteine, L-kynurenine and phenylalanine. Nine metabolites were positively correlated with proteinuria, including mesaconic acid, trans-cinnamic acid, fumaric acid, 5-thymidylic acid, anthranilic acid, indole, deoxyguanosine triphosphate, 13-cis-retinoic acid and nicotinamide riboside, while three metabolites were negatively correlated with proteinuria including acetoacetate, hypotaurine and hexanal. 'Phenylalanine metabolism' was the most significant pathway which was impaired in severe stage in comparison to mild stage of IgAN. This study indicates that nuclear magnetic resonance is a versatile technique that is capable of detecting metabolite biomarkers in combination with advanced multivariate statistical analysis. Copyright © 2017 John Wiley & Sons, Ltd.

1 H NMR-based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.

Which echocardiographic parameter is a better marker of volume status in hemodialysis patients?

AIM: Bio-impedance analysis (BIA) is a preferred method for estimating the volume status. However, it cannot be utilized in daily practice. Since the assessment of the volume status is important and challenging for hemodialysis (HD) patients, the aim of study was to determine the volume status in chronic HD patients using echocardiographic parameters and assess its correlation with BIA. METHODS: In this cross-sectional analysis, echocardiography and BIA were performed on 30 chronic HD patients 30 min before and 30 min after dialysis. All the cases of dialysis were performed in the middle of the week. This study also assessed the correlation between echocardiographic parameters and BIA parameters. RESULTS: There were significant differences between ECW, TBW, and TBW% (TBW/W) before and after HD. Significant differences were observed between echocardiographic parameters of IVCD, IVCDimin, IVCDimax before and after the HD. LVEDD, LVESD, LA area, mitral valve inflow, E/E', and IVRT, were improved after dialysis, too. There was a significant correlation between IVCDimin as an index of volume status, ECW% and TBW% before HD and IVCDimin change after dialysis had a significant correlation with %ECW change after dialysis. Comparison between hypertensive and non-hypertensive groups indicated IVCDimin was significantly lower in non-hypertensive group after dialysis. CONCLUSION: Our results showed a correlation between IVCDimin and BIA parameters before HD. So, it seems that IVCDimin can be a good parameter for determining the volume status of HD patients. However, further studies, with larger sample size and with a prospective study design, are required to confirm these results.

Predictive urinary biomarkers for steroid-resistant and steroid-sensitive focal segmental glomerulosclerosis using high resolution mass spectrometry and multivariate statistical analysis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a glomerular scarring disease diagnosed mostly by kidney biopsy. Since there is currently no diagnostic test that can accurately predict steroid responsiveness in FSGS, prediction of the responsiveness of patients to steroid therapy with noninvasive means has become a critical issue. In the present study urinary proteomics was used as a noninvasive tool to discover potential predictive biomarkers. METHODS: Urinary proteome of 10 patients (n = 6 steroid-sensitive, n = 4 steroid-resistant) with biopsy proven FSGS was analyzed using nano-LC-MS/MS and supervised multivariate statistical analysis was performed. RESULTS: Twenty one proteins were identified as discriminating species among which apolipoprotein A-1 and Matrix-remodeling protein 8 had the most drastic fold changes being over- and underrepresented, respectively, in steroid sensitive compared to steroid resistant urine samples. Gene ontology enrichment analysis revealed acute inflammatory response as the dominant biological process. CONCLUSION: The obtained results suggest a panel of predictive biomarkers for FSGS. Proteins involved in the inflammatory response are shown to be implicated in the responsiveness. As a tool for biomarker discovery, urinary proteomics is especially fruitful in the area of prediction of responsiveness to drugs. Further validation of these biomarkers is however needed.

Pericardial effusion in patients with chronic kidney disease: A two-center study.

BACKGROUND AND AIMS: Pericardial effusion (PE) is a prevalent form of pericardial involvement in chronic kidney disease (CKD). This study aims to investigate the clinical and laboratory features associated with PE severity in patients with CKD. METHODS: In this cross-sectional study, we examined the medical records of patients admitted to tertiary hospitals with International Classification of Diseases 10th Revision (ICD-10) codes associated with CKD and PE. We included 112 CKD patients in stage 4 and 5 non-dialysis (ND) with PE for assessing the clinical and laboratory features of severity. RESULTS: Patients were divided into two categories based on the severity of PE. Seventy-two patients had mild and 40 had moderate and severe PE. Univariate analysis of demographic and laboratory features on the date of admission demonstrated that chest pain, dyspnea, serum albumin, and neutrophil-to-lymphocyte ratio (NLR) are associated with the severity of PE. The univariate analysis on the date of echocardiography showed significantly higher white blood cell count (WBC), neutrophil count (percentage and absolute count), and NLR, along with significantly lower lymphocyte percentage and serum albumin among patients with moderate and severe PE. In the multivariable analysis of laboratory features, on admission hypoalbuminemia (p-value = 0.014, OR = 4.03, CI: 1.32-12.25) and NLR greater than 5.5 (p-value = 0.015, OR = 4.22, CI: 1.32-13.50) were significantly associated with moderate and severe PE. In a parallel matter, at the time of echocardiography hypoalbuminemia (p-value = 0.004, OR = 5.38, CI: 1.74-16.65) and neutrophilia (p-value = 0.005, OR = 7.94, CI: 1.89-33.44) were significantly associated with moderate and severe PE. CONCLUSION: Despite advancements in the diagnosis and treatment of CKD, PE is still a concerning issue in these patients. This study revealed that hypoalbuminemia, neutrophilia, and NLR greater than 5.5 could be predictive factors of moderate and severe PE in CKD patients with PE. Further prospective study with larger sample size is needed to confirm these results.

Tacrolimus Intrapatient Variability on Graft Outcomes in Adherent Renal Transplantation Patients: A Cross-Sectional Study.

INTRODUCTION: Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients. METHODS: In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated. RESULTS: Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P > .05).  However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively). CONCLUSION: Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients. DOI: 10.52547/ijkd.7815.

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.

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.

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.

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.

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.

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.

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.

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.