Benefits of Inactivated Vaccine and Viral Vector Vaccine Immunization on COVID-19 Infection in Kidney Transplant Recipients

The coronavirus virus disease 2019 (COVID-19) pandemic has impacted the global healthcare system. In Thailand, the first and most available vaccines were inactivated and viral vector vaccines. We reported the impact of those vaccines in preventing severe disease and death in kidney transplant recipients. This retrospective study comprised 45 kidney transplant recipients with COVID-19 infection, classified by vaccination status. Outcomes of interest were death, pneumonia, and allograft dysfunction. There were 23 patients in vaccinated group and 22 patients in unvaccinated group. All baseline characteristics were similar except mean age was older in vaccinated group, 55 vs. 48 years. Total 11 patients (24%) died (13% vaccinated vs. 36% unvaccinated RR, 0.56; 95% CI, 0.29–0.83; p = 0.03). Multivariate analysis showed that vaccination significantly decrease mortality (odds ratio, 0.54; 95% CI, 0.10–0.94; p = 0.03). Pneumonia developed equally in both groups (70%). There was a trend toward less oxygen requirement as well as ventilator requirement in vaccinated group. The rate of allograft dysfunction was similar (47%). Inactivated and viral vector COVID-19 vaccines have beneficial effect on mortality reduction in kidney transplant recipients. Even partial vaccination can exert some protection against death. However, full vaccination should be encouraged to achieve better prevention

Impact of self‐monitoring of salt intake by salt meter in hypertensive patients: A randomized controlled trial (SMAL‐SALT)

Abstract Salt intake over reference level would result in elevated blood pressure (BP) and long‐term morbidity. Salt meter is a device used to detect sodium content in daily food. This study aimed to evaluate the efficacy of salt‐meter addition to dietary education. The authors conducted a randomized‐controlled trial in hypertensive patients with uncontrolled BP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). Patients were randomized to receive salt meter plus dietary education (group A) or education only (group B), and followed up for 8 weeks. The primary endpoint was change in 24‐h urinary sodium excretion. Changes in BP, salt taste sensitivity, cardio‐ankle vascular index (CAVI) were also analyzed. There were total number of 90 patients who had complete follow‐up, 45 in each group. Mean age was 62.9 years and 53% were females. Mean baseline 24‐h urine sodium was 151.6 mmol/24 h and mean SBP and DBP were 152.8 and 83.4 mmHg, respectively. Baseline characteristics were similar between two groups. At 8 weeks, mean change in urine sodium were –31.83 mmol/24 h and 0.36 mmol/24 h in group A and group B, respectively (p = .006). Mean decrease in BP were SBP, 14.44 versus 8.22 mmHg (p = .030), and DBP 5.53 versus 1.93 mmHg (p = .032). The salt sensitivity was improved more in group A. There was no different between change in CAVI. From this study, salt meter in conjunction with dietary education, for self‐monitoring of salt intake is superior to education alone in hypertensive patients, and provided better blood pressure control. Salt meter should be considered in uncontrolled hypertensive patients

The Effect of a Booster Dose mRNA Vaccine on COVID-19 Infection in Kidney Transplant Recipients after Inactivated or Viral Vector Vaccine Immunization

The mortality rate after novel coronavirus infection, which causes severe acute respiratory distress syndrome (SARS-CoV-2), is much higher in kidney transplant recipients (KTRs) compared to the general population. Seroconversion after vaccination is also lower, and breakthrough infection is much higher. Many studies reported seroconversion rate after a booster (third) dose of vaccine but clinical outcomes received less attention. Here, we reported the impact of an mRNA vaccine booster dose on clinical outcomes of KTRs with SARS-CoV-2 infection. A total of 183 KTRs with SARS-CoV-2 infection were identified. Of 183 KTRs, 146 KTRs had sufficient data for analysis and were included in this study. Forty-eight patients (32.9%) received zero to 1 doses of vaccine (Group 1), thirty-one (21.2%) received two doses (Group 2), and sixty-seven (45.9%) received a booster dose (Group 3). Pneumonia developed in 50%, 23%, and 10% in Group 1, 2, and 3 (p < 0.001). Hospital admission requirement was 81%, 48%, and 12% (p < 0.001). Mortality rate was 26%, 3%, and 3% (p = 0.001). A multivariate analysis showed that only diabetes adversely affects mortality while the booster dose of the vaccine significantly reduced mortality. The booster dose of the vaccine is strongly recommended in all KTRs especially those with diabetes. Our study also suggested the timing of the booster dose vaccine to be administered within 4 months after the second dose

Clinical and immunological characteristics for BK polyomavirus‐associated nephropathy after kidney transplantation

Abstract Introduction BK polyomavirus (BKPyV)‐associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV‐specific immunity is associated with viral containment. This study investigated BKPyV‐specific immunological factors among KT recipients. Methods This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV‐cell‐specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon‐gamma (IFN‐γ)‐producing CD4+ T, CD8+ T, natural killer (NK), and natural killer T (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). Results In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1‐year cumulative incidence of high‐level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre‐KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077–1.469; p = .004) and %VP1‐specific NK cells (HR, 1.209; 95% CI, 1.055–1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1‐specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). Conclusion Individuals with nonspecific and VP1‐specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high‐level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV‐specific innate immune surveillance in predicting the occurrence of BKPyVAN

Vasopressin-induced activation of protein kinase C in renal epithelial cells

AbstractRecent studies indicate that the actions of arginine vasopressin (AVP) and other agonists that stimulate electrogenic sodium transport in renal epithelial A6 cells are linked to a Ca2+-mobilizing signal transduction mechanism that involves generation of inositol trisphosphate. Since diacylglycerol is the other product in this pathway, studies were performed to determine the possible role of PKC in the stimulation of sodium transport. AVP induced a biphasic increase in diacylglycerol generation, characterized by an initial rapid rise and then a sustained elevation, and PKC activation, reflected by phosphorylation of a specific 80 kDa myristoylated alanine-rich PKC substrate (MARCKS). To determine the PKC isoform(s) involved in this process, immunoblot analysis was performed using antisera that recognize both classical PKC isoforms, XPKC-I and XPCK-II, cloned from Xenopus oocytes. The transcripts of both isoforms were expressed in the A6 cell. Since protein recognized by antisera was translocated from cytosol to the particulate fraction after exposure to AVP, one or both isoforms were activated in the A6 cell. Further studies showed that cyclohexyladenosine and insulin, additional agonists of sodium transport in A6 cells, also stimulated phosphorylation of MARCKS. These results argue that Ca2+-dependent PKC is involved in the action of AVP, and that of other agonists, which stimulate sodium transport

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.BackgroundGenetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background.MethodsUsing a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH.ResultsGenome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 ± 9.5 vs. 91.8 ± 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH.ConclusionsOur study demonstrates the application of a transgene as a “major gene” to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype

Controlled hypertension, a transgenic toggle switch reveals differential mechanisms underlying vascular disease

A novel inbred rat model with inducible hypertension has been generated using a renin transgene under the transcriptional control of the cytochrome P450, Cyp1a1 promoter. The degree and duration of hypertension are regulated tightly by administration of the natural xenobiotic indole-3 carbinol and can be readily reversed. Induction experiments reveal distinct temporal and mechanistic responses to hypertensive injury in different vascular beds, which is indicative of differential susceptibility of organs to a hypertensive stimulus. The mesentery and heart exhibited the greatest sensitivity to damage, and the kidney showed an adaptive response prior to the development of malignant hypertensive injury. Quantitative analysis of morphological changes induced in mesenteric resistance arteries suggest eutrophic remodeling of the vessels. Kinetic evidence suggests that locally activated plasma prorenin may play a critical role in mediating vascular injury. This model will facilitate studies of the cellular and genetic mechanisms underlying vascular injury and repair and provide a basis for the identification of novel therapeutic targets for vascular disease