Introduction
The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated ...immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters.
Methods
We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs.
Heterologous regimen:
two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75).
Homologous vaccination
: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters.
Results
A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference.
Conclusion
switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.
We assessed the feasibility of ambulatory pulse wave analysis by comparing this approach with an established tonometric technique. We investigated 35 volunteers (45.6 years; 51.0% women) exclusively ...at rest (R study) and 83 volunteers (49.9 years; 61.4% women) at rest and during daytime (1000-2000 h) ambulatory monitoring (R+A study). We recorded central systolic (cSP), diastolic (cDP) and pulse (cPP) pressures, augmentation index (cAI) and pulse wave velocity (PWV) by brachial oscillometry (Mobil-O-Graph 24h PWA Monitor) and radial tonometry (SphygmoCor). We applied the Bland and Altman's statistics. In the R study, tonometric and oscillometric estimates of cSP (105.6 vs. 106.9 mm Hg), cDP (74.6 vs. 74.7 mm Hg), cPP (31.0 vs. 32.1 mm Hg), cAI (21.1 vs. 20.6%) and PWV (7.3 vs. 7.0 m s(-1)) were similar (P0.11). In the R+A study, tonometric vs. oscillometric assessment yielded similar values for cSP (115.4 vs. 113.9 mm Hg; P=0.19) and cAI (26.5 vs. 25.3%; P=0.54), but lower cDP (77.8 vs. 81.9 mm Hg; P<0.0001), so that cPP was higher (37.6 vs. 32.1 mm Hg; P<0.0001). PWV (7.9 vs. 7.4 m s(-1)) was higher (P=0.0002) on tonometric assessment. The differences between tonometric and oscillometric estimates increased (P0.004) with cSP (r=0.37), cAI (r=0.39) and PWV (r=0.39), but not (P0.17) with cDP (r=0.15) or cPP (r=0.13). Irrespective of measurement conditions, brachial oscillometry compared with an established tonometric method provided similar estimates for cSP and systolic augmentation, but slightly underestimated PWV. Pending further validation, ambulatory assessment of central hemodynamic variables is feasible.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The impact of habitual diet on chronic diseases has not been extensively characterized in South America. We aimed to identify major dietary patterns (DP) in an adult cohort in Uruguay (Genotype ...Phenotype and Environment of Hypertension Study—GEFA-HT-UY) and to assess associations with metabolic, anthropometric characteristics, and cardiovascular and kidney phenotypes. In a cross-sectional study (n = 294), DP were derived by the principal component analysis. Blood and urine parameters, anthropometrics, blood pressure, pulse wave velocity, and glomerular filtration rate were measured. Multivariable adjusted linear models and adjusted binary logistic regression were used. Three DP were identified (Meat, Prudent, Cereal and Mate) explaining 22.6% of total variance in food intake. The traditional Meat DP, characterized by red and barbecued meat, processed meat, bread, and soft drinks, was associated with worse blood lipid profile. Prudent DP, characterized by vegetables, fish, and nuts, and lower loads for bread and crackers, was associated with reduced risk of vitamin D deficiency. Cereal and Mate DP, was characterized by higher loads of cereals, bread, and crackers, and mate infusion, with higher odds of excessive body weight. No direct associations of dietary patterns with hypertension, arterial stiffness, chronic kidney disease, and nephrolithiasis were found in the studied population, nor by age categories or sex.
Our aim is to describe variations in the incidence rates of glomerular disease diagnosed by renal biopsies performed in Uruguay over the last 25 years in relation to sex, age, clinical presentation ...and histological diagnosis. We analyzed all renal biopsies performed in Uruguay during the 25 years period and estimated incidence rates per million people per year (pmp/yr) for the population older than 14 years. Mann Kendall's trend analysis was used to assess incidence trends. In order to identify changes in trends, we compared annual incidence rates with the Joinpoint method. From 1990 to 2014, 3390 biopsies of native kidneys corresponding to glomerular disease were performed in patients older than 14 years. The average biopsy rate was 58 per pmp/yr. The glomerular disease incidence rate increased progressively over the period (p<0.05). Trends analysis over five-year periods demonstrated a progressive increase of IgA nephropathy (3.08 pmp/yr 1990-1994 to 12.53 pmp/yr 2010-2014 p<0.05), membranous nephropathy (2.38 pmp/yr 1990-1994 to 8.04 pmp/yr 2010-2014 p< 0.05) and lupus nephritis (4,23 pmp/yr 1990-1994 to 7,81 pmp/yr 2010-2014 p<0.05). There was a change in the trend of focal segmental glomerular sclerosis (FSGS) which increased until 1996 and decreased afterwards. The incidence rates of glomerular disease have doubled globally in the last quarter of a century in Uruguay, mainly related to the increase of IgA nephropathy, membranous nephropathy and lupus nephritis. There was a change in the slope of the incidence rate of FSGS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment.
A retrospective ...analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy ESKD/KRT or all-cause death) were obtained from mandatory national registries.
The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors.
The IS group had more severe risk factors than the NoIS group but attained a similar outcome.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hypertension and its consequences, including heart failure, stroke, and kidney disease, are responsible for substantial morbidity and mortality worldwide. Lifestyle changes, particularly sodium ...reduction, contribute to blood pressure control. However, not all individuals, whether normotensive or hypertensive, have the same susceptibility to the effects of salt. While a variety of approaches have been proposed to identify salt sensitive patients, there is no consensus for a definition of salt sensitivity and the precise mechanisms that explain their association are not yet fully understood. In this review we summarize the current understanding of the various pathophysiological mechanisms potentially involved in determining the salt sensitive phenotype. Genetic, neuronal, and immune alterations are reviewed. Additionally, we provide an update on the current knowledge of a new approach proposing the interstitium of the skin may act as a sodium reservoir. The role of dietary potassium on salt sensitive hypertension is also summarized.
Hypertension is a frequent and modifiable cardiovascular risk factor with a cyclic relationship with chronic kidney disease (CKD). The diagnosis, treatment, monitoring and control of high blood ...pressure are all mandatory not only in CKD but also in end-stage renal disease (ESRD). As demonstrated by studies using population and hypertensive patients, white-coat hypertension (WCHT) and masked hypertension (MHT) carry a particular degree of risk. The advantages of ambulatory techniques in the management and prognostic stratification of patients with CKD and ESRD have also been recognized. However, most of the evidence underlines the importance of nocturnal hypertension and neglects WCHT and MHT. The absence of specific reports involving untreated and treated patients hinders the ability to significantly discriminate WCHT from the white-coat effect and MHT from masked uncontrolled hypertension. The heterogeneous definitions that are used add additional difficulty in translating experimental evidence into clinical practice. Reaching a consensus in definitions is mandatory for designing future research. Cross-sectional studies underscore the frequency of misdiagnosis, potentially leading to undertreatment (MHT) and overtreatment (WCHT) in renal disease. The divergent prevalence of WCHT and MHT reported in CKD could be related to the diverse definitions of hypertension and the heterogeneity of the pathologies pooled under the CKD definition. Even in the absence of randomized clinical trials specifically addressing this issue, the scarce longitudinal studies confirm that WCHT carries a risk close to that of sustained normotension, whereas MHT is associated with a risk close or identical to that of sustained hypertension.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged ...as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats.
This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation.
Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model.
Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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