We investigated whether urinary vascular non-inflammatory molecule-1 (vanin-1), a promising early-onset tubular injury marker, correlates with other established tubular injury markers and is ...associated with graft failure in kidney transplant recipients (KTR). We measured 24 h urinary vanin-1 excretion in 656 KTR (age 53 ± 13 years, 43% female, estimated glomerular filtration rate (eGFR) 53 ± 21 mL/min/1.73 m
) who had undergone kidney transplantation ≥ 1 year. The median 24 h urinary vanin-1 excretion was 145 51-331 pmol/24 h. 24 h urinary vanin-1 excretion correlated weakly but significantly with other tubular injury markers (ρ = 0.14, p < 0.001 with urinary liver-type fatty acid binding protein, ρ = 0.13, p = 0.001 with urinary post-translationally modified fetuin-A protein, and ρ = 0.10, p = 0.011 with plasma neutrophil gelatinase-associated lipocalin) and with eGFR (ρ = - 0.13, p = 0.001). During a median follow-up of 7.4 4.9-8.0 years, 94 (14%) KTR developed death-censored graft failure. In multivariable Cox regression analyses, 24 h urinary vanin-1 excretion was not associated with an increased risk of death-censored graft failure (adjusted hazard ratio 95% confidence interval = 0.96 0.86-1.07, p = 0.5). In conclusion, our findings do not support the role of urinary vanin-1 as a biomarker of graft failure after kidney transplantation.
Most transplant centers in the Netherlands use estimated glomerular filtration rate (eGFR) for evaluation of potential living kidney donors. Whereas eGFR often underestimates GFR, especially in ...healthy donors, measured GFR (mGFR) allows more precise kidney function assessment, and therefore holds potential to increase the living donor pool. We hypothesized that mGFR-based donor screening leads to acceptance of donors with lower pre-donation eGFR than eGFR-based screening. In this longitudinal cohort study, we compared eGFR (CKD-EPI) before donation in one center using mGFR-based screening (mGFR-cohort, n = 250) with two centers using eGFR-based screening (eGFR-cohort1, n = 466 and eGFR-cohort2, n = 160). We also compared differences in eGFR at five years after donation. Donor age was similar among the cohorts (mean±standard deviation (SD) mGFR-cohort 53±10 years, eGFR-cohort1 52±13 years, P = 0.16 vs. mGFR-cohort, and eGFR-cohort2 53±9 years, P = 0.61 vs. mGFR-cohort). Estimated GFR underestimated mGFR by 10±12 mL/min/1.73m.sup.2 (mean±SD), with more underestimation in younger donors. In the overall cohorts, mean±SD pre-donation eGFR was lower in the mGFR-cohort (91±13 mL/min/1.73m.sup.2) than in eGFR-cohort1 (93±15 mL/min/1.73m.sup.2, P<0.05) and eGFR-cohort2 (94±12 mL/min/1.73m.sup.2, P<0.05). However, these differences disappeared when focusing on more recent years, which can be explained by acceptance of more older donors with lower pre-donation eGFR over time in both eGFR-cohorts. Five years post-donation, mean±SD eGFR was similar among the centers (mGFR-cohort 62±12 mL/min/1.73m.sup.2, eGFR-cohort1 61±14 mL/min/1.73m.sup.2, eGFR-cohort2 62±11 mL/min/1.73m.sup.2, P = 0.76 and 0.95 vs. mGFR-cohort respectively). In the mGFR-cohort, 38 (22%) donors were excluded from donation due to insufficient mGFR with mean±SD mGFR of 71±9 mL/min/1.73m.sup.2. Despite the known underestimation of mGFR by eGFR, we did not show that the routine use of mGFR in donor screening leads to inclusion of donors with a lower pre-donation eGFR. Therefore eGFR-based screening will be sufficient for the majority of the donors. Future studies should investigate whether there is a group (e.g. young donors with insufficient eGFR) that might benefit from confirmatory mGFR testing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death ...in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury.
Methods
This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (
n
= 6) and bacterial sepsis (
n
= 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (
n
= 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients.
Results
We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42,
p
= 0.0002) and bacterial sepsis patients (fold change 0.24,
p
< 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3,
p
= 0.0006, PV-1 fold change 1.5,
p
= 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27,
p
< 0.0001) and bacterial sepsis patients (fold change 0.67,
p
< 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33,
p
= 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09,
p
< 0.0001) suggest decreased microvascular flow in COVID-19.
Conclusions
In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.
Recent developments, improvements, and trends in the ultra-trace determination of per- and polyfluoroalkyl substances (PFASs) in environmental and human samples are highlighted and the remaining ...challenges and uncertainties are outlined and discussed. Understanding the analytical implications of such things as adsorption of PFASs to surfaces, effects of differing matrices, varying PFAS isomer response factors, potential bias effects of sampling, sample preparation, and analysis is critical to measuring highly fluorinated compounds at trace levels. These intricate analytical issues and the potential consequences of ignoring to deal with them correctly are discussed and documented with examples. Isomer-specific analysis and the development of robust multi-chemical methods are identified as topical trends in method development for an ever-increasing number of PFASs of environmental and human interest. Ultimately, the state-of-the-art of current analytical method accuracy is discussed on the basis of results from interlaboratory comparison studies.
Figure
Separation of the linear, mono-trifluoromethyl branched, and di-trifluoromethyl branched structural isomers of PFOS and PFOA by ultra-performance liquid chromatography using a conventional C18 reversed-phase column. The PFOS and PFOA structural isomers were detected by tandem mass spectrometry
Pregnancy after solid organ transplantation (SOT) has potential risks for the offspring. Most existing research focused on short-term pregnancy outcomes. The aim of this systematic review was to ...evaluate available data concerning longer term outcomes (>1 year) of these children. A systematic literature search, following PRISMA guidelines, of PubMed and Embase was performed from the earliest date of inception through to 6th April 2022. Publications on all types of (combined) SOT were eligible for inclusion. In total, 53 articles were included. The majority assessed offspring after kidney (78% of offspring) or liver transplantation (17% of offspring). 33 studies included offspring aged >4 years and five offspring aged >18 years. One study was included on fathers with SOT. The majority of the 1,664 included children after maternal SOT had normal intellectual, psychomotor, and behavioral development. Although prematurity and low birth weight were commonly present, regular growth after 1 year of age was described. No studies reported opportunistic or chronic infections or abnormal response to vaccinations. In general, pregnancy after SOT appears to have reassuring longer term outcomes for the offspring. However, existing information is predominantly limited to studies with young children. Longer prospective studies with follow-up into adulthood of these children are warranted.
Elderly kidney transplant recipients (KTRs) represent almost one third of the total kidney transplant population. These patients have a very high coronavirus disease 2019 (COVID-19)-related ...mortality, whereas their response to COVID-19 vaccination is impaired. Finding ways to improve the COVID-19 vaccination response in this vulnerable population is of uttermost importance.
In the OPTIMIZE trial, we randomly assign elderly KTRs to an immunosuppressive regimen with standard-exposure calcineurin inhibitor (CNI), mycophenolate mofetil, and prednisolone or an adapted regimen with low dose CNI, everolimus, and prednisolone. In this substudy, we measured the humoral response after 2 (N = 32) and 3 (N = 22) COVID-19 mRNA vaccinations and the cellular response (N = 15) after 2 vaccinations.
. The seroconversion rates of elderly KTRs on a standard immunosuppressive regimen were only 13% and 38% after 2 and 3 vaccinations, respectively, whereas the response rates of KTRs on the everolimus regimen were significantly higher at 56% (P = 0.009) and 100% (P = 0.006). Levels of severe acute respiratory syndrome coronaVirus 2 IgG antibodies were significantly higher at both time points in the everolimus group (P = 0.004 and P < 0.001). There were no differences in cellular response after vaccination.
. An immunosuppressive regimen without mycophenolate mofetil, a lower CNI dose, and usage of everolimus is associated with a higher humoral response rate after COVID-19 vaccination in elderly KTRs after transplantation. This encouraging finding should be investigated in larger cohorts, including transplant recipients of all ages.
Objectives Monitoring tacrolimus blood concentrations is important for preventing allograft rejection in transplant patients. Our hospital offers dried blood spot (DBS) sampling, giving patients the ...opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. In this study, both a volumetric absorptive microsampling (VAMS) device and DBS sampling were compared to venous whole blood (WB) sampling. Methods A total of 130 matched fingerprick VAMS, fingerprick DBS and venous WB samples were obtained from 107 different kidney transplant patients by trained phlebotomists for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. A multidisciplinary team pre-defined an acceptance limit requiring >80% of all matched samples within 15% of the mean of both samples. Sampling quality was evaluated for both VAMS and DBS samples. Results 32.3% of the VAMS samples and 6.2% of the DBS samples were of insufficient quality, leading to 88 matched samples fit for analysis. Passing-Bablok regression showed a significant difference between VAMS and WB, with a slope of 0.88 (95% CI 0.81-0.97) but not for DBS (slope 1.00; 95% CI 0.95-1.04). Both VAMS (after correction for the slope) and DBS showed no significant bias in Bland-Altman analysis. For VAMS and DBS, the acceptance limit was met for 83.0% and 96.6% of the samples, respectively. Conclusions VAMS sampling can replace WB sampling for tacrolimus trough concentration monitoring, but VAMS sampling is currently inferior to DBS sampling, both regarding sample quality and agreement with WB tacrolimus concentrations.
FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample ...sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.
The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.
Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval 95% CI, 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio HR, 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m
; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.
Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Measuring vibration perception threshold (VPT) accurately classifies and quantifies the severity of loss of vibration perception. A biothesiometer (Bio-thesiometer.sup.#174; ; Bio Medical Instrument ...Co, Ohio, USA) appears to be the most suitable tool to determine VPT due to its low inter-rater variability and low occurence of adaption to the sensation. Different VPT values for a biothesiometer have been described, however, specification on age, height and different measurement locations is currently lacking. The objective of our study was to identify determinants of vibration perception in non-diabetic subjects, in order to provide individualized normal values of VPTs for clinical practice. Measurements of the vibration perception were performed on the big toes, insteps, lateral malleoli, and wrists. A total of 205 healthy subjects were included (108 (52.7%) males) with a median interquartile range age of 59 51;64 (range 21-80) years. Mean height was 174.45 #177; 9.20 cm and mean weight was 82.94 #177; 14.84 kg, resulting in a mean BMI of 27.19 #177; 4.00 kg/m.sup.2 . In stepwise forward linear regression analyses, age (st. beta = 0.51, p 0.001) and height (st. beta = 0.43, p 0.001) were found to be the independent unmodifiable determinants of the VPT at the big toe. Regression coefficients for quantiles of the determinants age and height were incorporated in the corresponding regression equations. This study provides equations to calculate age- and height-specific normal values for VPT that can be used in clinical practice and in large research studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study focused on the value of quantitatively analyzed and qualitatively graded renal scintigraphy in relation to the expected duration of delayed graft function after kidney transplantation. A ...more reliable prediction of delayed graft function duration may result in a more tailored and patient-specific treatment regimen post-transplantation.
From 2000 to 2014, patients with early transplant dysfunction and a Tc-99m MAG3 renal scintigraphy, within 3 days post-transplantation, were included in a dual center retrospective study. Time-activity curves of renal scintigraphy procedures were qualitatively graded and various quantitative indices (R20/3, TFS, cTER, MUC10) were combined with a new index (Average upslope). The delayed graft function duration was defined as the number of days of dialysis-based/functional delayed graft function.
A total of 377 patients were included, with a mean age (± SD) of 52 ± 14 years, and 58% were male. A total of 274 (73%) patients experienced delayed graft function≥ 7 days. Qualitative grading for the prediction of delayed graft function≥ 7 days had a sensitivity and specificity of respectively 87% and 65%. The quantitative indices with the most optimal results were cTER (76% sensitivity, 72% specificity), and Average upslope (75% sensitivity, 73% specificity).
Qualitative renal scintigraphy grading and the quantitative indices cTER and Average upslope predict delayed graft function ≥ 7 days with a high sensitivity. This finding may help to support both clinicians and patients in managing early post-operative expectations. However, the specificity is limited and thus renal scintigraphy does not reliably help to identify patients in whom the course of delayed graft function is longer than anticipated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
