Infection induced kidney diseases are of concern for clinicians because timely detection and treatment of infections may cure or limit the extent of injury inflicted by microorganisms causing the infections. Infections can cause kidney injury by either direct invasion, or indirectly by immune mediated mechanisms, which manifest as post-infectious glomerulonephritis, or infection-related glomerulonephritis. Clinical manifestations may be acute or chronic depending on the microorganisms, endemic/epidemic nature and source of infection. All microbials virus, bacteria, mycobacteria, fungus, and protozoa have been implicated in kidney diseases either causing direct kidney injuries or immune-mediated injuries. Infection control practices in large parts of world is limited by poverty, social behavior, high population density, deforestation, inadequate access to safe drinking water, and poor health care facilities. Although, antimicrobials and vaccinations have successfully eradicated and cured many infectious diseases; however injudicious antimicrobial use and emergence of resistant organisms complicated the disease severity like secondary renal amyloidosis with chronic persistent infection. Re-emergence of various infections has been a recent pattern in developed world leading to uncertain diagnostic challenges, and association with kidney diseases.
IntroductionVascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) −1154 G/A, −2578 C/A, +936 C/T, and −2549 Ins/Del in chronic allograft nephropathy.MethodsBlood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs −1154 G/A (rs1570360), −2578 C/A (rs699947), +936 C/T (rs112005313), and −2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2−ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy−Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan−Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies.ResultsThere was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of −2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs −2578 C/A and −2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF −2578 C/A SNP. The carrier −2578*CC, −1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas.ConclusionRecipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival.
Vaccination-induced SARS-CoV-2 neutralizing antibodies are required for herd immunity. Vaccine availability and poor vaccine response in renal transplant recipients (RTRs) remain a concern. There is no report on the efficacy of Covaxin and Covishield vaccines in RTRs. We recruited 222 live donors RTRs and analyzed the serum titer of anti-SARS-CoV-2 spike protein antibody by chemiluminescent magnetic microparticle immunoassay. Patients were categorized into three groups: group1 with SARS-CoV-2 infection and no vaccination (n = 161); group 2 with only vaccination and no SARS-CoV-2 infection (n = 41); and group 3 with both vaccination and SARS-CoV-2 infection (n = 20). Overall seroconversion rate was 193/222 (86.9%) with a median titer 1095.20 AU/mL. The median IgG titer value in group 1 was 647.0 AU/mL; group 2 was 1409.0 AU/mL; and group 3 was 1831.30 AU/mL. Covaxin associated seroconversion was observed in 16/19 (84.21%), with a median titer of 1373.90 AU/mL compared to that of Covishield 32/42 (76.19%), whose median titer was 1831.10 AU/mL. The seroconversion rate due to SARS-CoV-2 infection was 145 (90.06%), it was lowest with the vaccination-only group (70.7%), and with both vaccination and SARS-CoV-2 infection group it was highest (95%). In RTRs, SARS-CoV-2 infection and both Covaxin and Covishield vaccination effectively induce a humoral immune response against the SARS-CoV-2 spike protein; however, seroconversion rate was lower and the antibody titer was higher with vaccine than infection.
Introduction: Vitamin D deficiency can impact post-transplant outcomes due to its effect on graft function and rejection. The effect of pre-and post-transplant serum vitamin D levels was evaluated on graft function. Objectives: This study aims to determine the incidence of vitamin D deficiency and its effect on post kidney transplant allograft function in a North Indian cohort. Patients and Methods: We evaluated 57 patients on dialysis, going for transplantation. Estimated glomerular filtration rate (eGFR) was measured using modification of diet in renal disease (MDRD) formula at 2 weeks and 3, 6, 12 months interval after kidney transplantation. Results: Pre-and post-transplant (3 months) vitamin D levels were evaluated for vitamin D deficiency and graft function. Before transplant vitamin D levels were 25.77 ± 13.68 ng/mL, 40.4% of these recipients had vitamin D deficiency (levels <20 ng/mL). After transplant, vitamin D levels at 3 months were 22.08 ± 11.15 ng/mL and 54.4% of recipients had vitamin D deficiency. No patient was on vitamin D supplementation after transplantation. At 3 months post-transplant, recipients with vitamin D levels <20 ng/mL, had significantly lower eGFR and higher serum creatinine value as compared to the group with vitamin D levels >20ng/mL. Recipients were divided into 3 groups based on pre-and post-transplant vitamin D levels (<20, 20-30 and >30ng/mL). Pre-transplant vitamin D levels correlated with graft function at 14 days. On multiple regression analysis, 3-month post-transplant vitamin D levels correlated with 12 months eGFR. There was increased incidence of acute rejection episodes in vitamin D deficiency group. Conclusion: There is a high incidence of vitamin D deficiency and insufficiency in kidney transplant recipients. Low levels of post-transplant vitamin D levels at 3 months were associated with inferior allograft function (eGFR) at 1 year.
Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/ml, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/ml, which was not significant between the two groups (P = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.
Site-selective ring-opening process of two different aziridine classes with hydroperoxide is described herein that provides access to various α-and β-amino and α-(imino)-peroxy compounds. This strainrelease-driven peroxide addition to aziridines represents an alternative approach for entries to biologically significant heteroatom substituted organic peroxides and complements existing methods in the field. The peroxide products obtained by this method displayed a different reactivity during peroxide-specific rearrangement processes promoted by either acid or base. Mechanistic studies and useful synthetic elaboration of the products have also been presented.
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