Kidney transplantation is the treatment of choice for patients with end-stage renal disease, and leads to everyday self-management of this chronic condition. This article aims to provide ...documentation for a participatory design study of a telehealth solution to improve the kidney transplantation process, and to identify the impact from the different participants in the participatory design study. Through a participatory design approach, a smartphone application (app) was developed for the entire kidney transplantation process together with a workflow for post-transplantation follow-up. A core element in participatory design is user involvement. By way of workshops and laboratory tests, the telehealth solution was developed in close cooperation with patients, their families, healthcare professionals, kidney association representatives, and Information Technology designers. The participatory design approach means that the telehealth solution was designed to be functional in a clinical setting, address patients’ needs, and support their self-management.
Aim
Activation of sodium reabsorption by urinary proteases has been implicated in sodium retention associated with nephrotic syndrome. The study was designed to test the hypothesis that nephrotic ...proteinuria in mice after conditional deletion of podocin leads to urokinase‐dependent, amiloride‐sensitive plasmin‐mediated sodium and water retention.
Methods
Ten days after podocin knockout, urine and faeces were collected for 10 days in metabolic cages and analysed for electrolytes, plasminogen, protease activity and ability to activate γENaC by patch clamp and western blot. Mice were treated with amiloride (2.5 mg kg−1 for 2 days and 10 mg kg−1 for 2 days) or an anti‐urokinase‐type plasminogen activator (uPA) targeting antibody (120 mg kg−1/24 h) and compared to controls.
Results
Twelve days after deletion, podocin‐deficient mice developed significant protein and albuminuria associated with increased body wt, ascites, sodium accumulation and suppressed plasma renin. This was associated with increased urinary excretion of plasmin and plasminogen that correlated with albumin excretion, urine protease activity co‐migrating with active plasmin, and the ability of urine to induce an amiloride‐sensitive inward current in M1 cells in vitro. Amiloride treatment in podocin‐deficient mice resulted in weight loss, increased sodium excretion, normalization of sodium balance and prevention of the activation of plasminogen to plasmin in urine in a reversible way. Administration of uPA targeting antibody abolished urine activation of plasminogen, attenuated sodium accumulation and prevented cleavage of γENaC.
Conclusions
Nephrotic range glomerular proteinuria leads to urokinase‐dependent intratubular plasminogen activation and γENaC cleavage which contribute to sodium accumulation.
Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from nephrotic rats and from patients with nephrotic syndrome activate ...the epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells and in Xenopus laevis oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a urinary serine protease by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. Purified plasmin activated ENaC currents, and inhibitors of plasmin abolished urinary protease activity and the ability to activate ENaC. In nephrotic syndrome, tubular urokinase-type plasminogen activator likely converts filtered plasminogen to plasmin. Consistent with this, the combined application of urokinase-type plasminogen activator and plasminogen stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC gamma subunit ectodomain. These data suggest that a defective glomerular filtration barrier allows passage of proteolytic enzymes that have the ability to activate ENaC.
Renal transplantation is the preferred treatment of end stage renal disease, but allograft survival is limited by the development of interstitial fibrosis and tubular atrophy in response to various ...stimuli. Much effort has been put into identifying new protein markers of fibrosis to support the diagnosis. In the present work, we performed an in-depth quantitative proteomics analysis of allograft biopsies from 31 prevalent renal transplant patients and correlated the quantified proteins with the volume fraction of fibrosis as determined by a morphometric method. Linear regression analysis identified four proteins that were highly associated with the degree of interstitial fibrosis, namely Coagulation Factor XIII A chain (estimate 18.7, adjusted
< 0.03), Uridine Phosphorylase 1 (estimate 19.4, adjusted
< 0.001), Actin-related protein 2/3 subunit 2 (estimate 34.2, adjusted
< 0.05) and Cytochrome C Oxidase Assembly Factor 6 homolog (estimate -44.9, adjusted
< 0.002), even after multiple testing. Proteins that were negatively associated with fibrosis (
< 0.005) were primarily related to normal metabolic processes and respiration, whereas proteins that were positively associated with fibrosis (
< 0.005) were involved in catabolic processes, cytoskeleton organization and the immune response. The identified proteins may be candidates for further validation with regards to renal fibrosis. The results support the notion that cytoskeleton organization and immune responses are prevalent processes in renal allograft fibrosis.
Solid organ transplant (SOT) recipients have shown suboptimal antibody response following COVID-19 vaccination. Several risk factors for the diminished response have been identified including ...immunosuppression and older age, but the influence of different comorbidities is not fully elucidated.
This case-control study consisted of 420 Danish adult SOT recipients and 840 sex- and age-matched controls, all vaccinated with a third homologous dose of either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. The primary outcome was differences in humoral immune response. The secondary outcome was breakthrough infections. Additionally, we looked for factors that could predict possible differences between the two groups.
Response rate increased from 186/382 (49%) to 275/358 (77%) in SOT recipients and remained on 781/790 (99%) to 601/609 (99%) in controls following a third vaccine dose. SOT recipients had significantly lower median antibody concentrations after third dose compared to controls (332.6 BAU/ml vs 46,470.0 BAU/ml, p <0.001). Lowest median antibody concentrations were seen in SOT recipients with liver disease (10.3 BAU/ml, IQR 7.1-319) and diabetes (275.3 BAU/ml, IQR 7.3-957.4). Breakthrough infections occurred similarly frequent, 150 (40%) among cases and 301 (39%) among controls (p = 0.80).
A third COVID-19 vaccine dose resulted in a significant increase in humoral immunogenicity in SOT recipients and maintained high response rate in controls. Furthermore, SOT recipients were less likely to produce antibodies with overall lower antibody concentrations and humoral immunity was highly influenced by the presence of liver disease and diabetes. The prevalence of breakthrough infections was similar in the two groups.
Interleukin-8 (IL-8) has been associated with ischemia reperfusion injury after renal allograft transplantation. Impaired allograft function may cause major impact on patient morbidity and health ...care costs. We investigated whether transcript levels in mononuclear cells including IL-8 on the first postoperative day may be involved in immediate allograft dysfunction as defined by reduced relative change in plasma creatinine at the first postoperative day.
We performed a single center, prospective-cohort study of 113 patients receiving kidney transplants. Peripheral blood mononuclear cells were harvested within 24 hours after transplantation. Transcripts were measured using quantitative RT-PCR.
Transcript levels of IL-8 and S100A8 were significantly lower in patients with relative change in plasma creatinine less than 10% at the first postoperative day. Receiver-operator characteristic curves showed that IL-8 predicted the relative change in plasma creatinine less than 10% (area under curve (AUC), 0.80; P = 0.0007). Multivariate analyses showed that lower IL-8 transcripts, longer time on dialysis, higher recipient body mass index and deceased donor type were associated with relative change in plasma creatinine at the first postoperative day less than 10%.
Reduced levels of IL-8 transcripts in peripheral mononuclear cells predict immediate graft dysfunction and delayed graft function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Contrast-enhanced CT (CECT) is widely used for diagnostic purposes. The use of contrast medium carries a risk for postcontrast acute kidney injury (PC-AKI), especially in patients with ...AKI or chronic kidney disease (CKD). Current guidelines recommend prophylactic intravenous hydration to prevent PC-AKI in high-risk patients. Oral hydration is non-inferior to intravenous hydration in patients with moderate CKD, but it has not been evaluated in high-risk patients.
Methods and analysis
The ENRICH trial will enrol 254 patients with estimated glomerular filtration rate ≤30 mL/min/1.73 m
2
undergoing intravenous CECT, who are block randomised (2-4-2) with stratification for CKD stage, diabetes status, and indication for referral to prophylactic treatment with oral or intravenous hydration. PC-AKI is defined as an absolute increase in SCr of >0.3 mg/dL or >1.5 from baseline at 2–5 days. Renal function will also be evaluated <90 days, <7 days and 1–3 days before intravenous CECT, and 25–40 days after intravenous CECT. Secondary outcomes include dialysis, renal adverse events, hospitalisation due to hydration-related or contrast-related sequelae, and all-cause mortality ≤30 days postcontrast. Pre- and postcontrast plasma and urinary biomarkers will be evaluated for diagnostic and prognostic accuracy of the primary and secondary outcomes.
Ethics and dissemination
Oral hydration is patient-friendly and less costly compared with intravenous hydration. If oral hydration is non-inferior to intravenous hydration in high-risk patients, it could be implemented as new hydration strategy, which will facilitate the clinical diagnosing of elective patients with severe CKD without unnecessary resource utilisation. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20210126), and the Data Protection Agency (21/66779). The study is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported in international peer-reviewed journals.
Trial registration number
NCT05283512
.
In solid organ transplant (SOT) recipients, the humoral response following COVID-19 vaccination is reduced, as a result of their immunosuppressed treatment. In this study, we investigated antibody ...concentrations after booster vaccinations until the fifth dose, the latter by monovalent or bivalent BA1 or BA4/5 vaccines. In addition, we evaluated the efficacy of vaccination by recording breakthrough infections, hospitalizations, and deaths.
This prospective cohort study included 438 SOT recipients (>18 years) vaccinated with mRNA vaccines against COVID-19 from January 2021 until March 2023. Blood samples were drawn before and after each vaccination and tested for SARS-CoV-2 spike RBD IgG antibodies with the lowest and highest cut-off at 7.1 and 5,680 BAU/mL, respectively. Vaccine information, breakthrough infections, and hospitalizations were collected from the medical records.
Most participants received BNT162b2 and 61.4% received five vaccine doses. The response proportion in SOT recipients increased from 86.7% after the fourth dose to 93.0% following the fifth dose. Antibody concentration decreased with 142.7 BAU/mL between the third and fourth dose (median 132 days, Quartile 1: 123, Quartile 3: 148) and 234.3 BAU/mL between the fourth and fifth (median 250 days, Quartile 1: 241, Quartile 3: 262) dose among those without breakthrough infection (p=0.34). When comparing the Omicron BA.1 or Omicron BA.4/BA.5 adapted vaccines, no significant differences in antibody concentration were found, but 20.0% of SOT recipients receiving a monovalent fifth vaccine dose had a breakthrough infection compared to 4.0% and 7.9% among those who received BA.1 and BA.4/BA.5 adapted vaccines, respectively (p=0.04). Since January 2021, 240 (54.8%) participants had a breakthrough infection, and 22 were hospitalized, but no deaths were observed.
The fifth COVID-19 vaccine dose raised antibody response to 93.0% of the study population. Additional booster doses, as well as bivalent vaccines, led to higher levels of antibody concentration in SOT recipients. We found a lower incidence of breakthrough infections among SOT recipients after receiving a bivalent vaccine as a fifth dose compared to those receiving a monovalent dose. Antibody concentrations did not wane when the time between doses was prolonged from four to eight months.
Kidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. ...Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation. The Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles. The study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim and objective
To explore living kidney donors' experiences during the donor evaluation process.
Background
Due to a shortage of organs for kidney transplantation from deceased donors, the living ...kidney donation rate has increased. The time period until transplantation is often shorter when using living donors compared to deceased donors. Although technological developments in immunology have made it possible to perform successful kidney transplants between donors and recipients, a large disparity still exists between the number of patients needing a kidney transplant and the supply of kidneys from living donors. This need has promoted donation from living kidney donors. The evaluation phase prior to donation is a crucial period in the recruitment of living kidney donors, as it ensures that donors are physically and mentally suitable for donation.
Design
A qualitative study taking a phenomenological‐hermeneutic approach.
Methods
Data were generated using participant observation during the evaluation period and semi‐structured interviews after conclusion of the evaluation. In total, 18 potential donors were included. Data were interpreted and discussed in accordance with Ricoeur's theory of interpretation: naïve reading, structural analysis, critical interpretation and discussion.
Results
Feelings of hope concerning acceptance as a donor and concerns for the recipient's illness and everyday life were evident during evaluation. Donors' experiences largely depended on the quality of their communication and interaction with the healthcare professionals. In some cases, donors were supported and cared for, while in other cases, frustrations and vulnerability were evident and emotional support and attention to donors' needs were not present.
Conclusion
The evaluation period for living kidney donation involves hope, vulnerability and concern. Interaction, communication and support from healthcare professionals to help donors manage this crucial phase are essential. Accordingly, the identification of donors' specific care and support needs, including physical, mental and ethical factors, is key to a positive experience.
Relevance to clinical practice
The attention, commitment and engagement of healthcare professionals are essential elements in the identification of donors' individual needs.
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