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  • 1
    In: Kidney International, Elsevier BV, Vol. 100, No. 2 ( 2021-08), p. 336-348
    Type of Medium: Online Resource
    ISSN: 0085-2538
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2007940-0
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  • 2
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 36, No. Supplement_1 ( 2021-05-29)
    Abstract: Hyperkalemia is common in patients on hemodialysis (HD) and in cardiorenal patients on RAAS inhibitors. Frequently, hyperkalemia is a leading reason to withdraw potentially lifesaving therapy in cardiorenal patients. Out-patient monitoring of plasma K+ levels due to preanalytical problems has proven problematic. The present pilot-study examined salivary K+ levels and kinetics based on plasma K+ measurements in HD patients employing a novel class of genetically-encoded fluorescent potassium-ion indicators, the GEPIIs (Bischof et al. Nat. Commun. 2017). HD patients represent a unique population in whom significant K+ derangements and rapid K+ level changes predictably occur and where these phenomena can be safely investigated. Method K+ assessments were performed in healthy individuals (n=20) and HD patients (n=30). Study-related procedures were approved by the local Institutional Review Board. Healthy individuals were recruited on a voluntary basis and provided only saliva samples. HD patients were recruited from our HD unit. Blood and saliva samples for K+ assessment were collected simultaneously during three consecutive HD sessions (HD1-3) prior to and directly after each session (pre/post HD). Blood was drawn in a standardized procedure directly from the HD access line and plasma K+ was measured immediately using standardized ion-selective electrodes (ISE). Saliva samples were gathered in a standardized procedure using a commercially available collection device (SuperSALTM). Of note, gaining adequate amounts of saliva from chronic HD patients, who frequently suffer from xerostomia, has proven challenging in some cases. The K+ content of saliva samples was measured by ISE and GEPII-technique. For the latter, samples were mixed with purified GEPIIs and were inserted into a fluorescent plate-reader. Probes were illuminated at 430 nm and emission light were collected at 475 nm and 525 nm, respectively. The ratio of the fluorescent intensities (F535/F480) after appropriate calibration is a direct measure of the K+ concentration sensed by GEPIIs. Results K+ determination in saliva samples using the GEPII-technique and ISE showed a strong agreement ((Figure 1A), Bias 0,71; 95% limits of agreement from -2.79 to 4.40). Pre-dialytic [K+]saliva of HD patients compared to healthy individuals, was higher (40,64±1,50 vs. 23,15±0,76 mmol/l, p & lt;0.05). As expected, each HD session (HD1-3) led to a significant reduction in [K+]plasma, which is followed by a similar, significant reduction of [K+] saliva (Figure 1B). Dynamics of plasma and salivary [K+] showed a very similar pattern: strong reduction during a HD session followed by a marked increase in the dialysis-free period until the next session 48-72h later (Figure 1C). Although basal [K+] saliva shows individual variations, [K+]Saliva and [K+] plasma exhibited a tendency of linear association (Figure 1D). Correlation analysis in each HD session (HD1-3 pre/post) revealed however no or weak correlation of pre- and post-dialytic saliva and plasma K+ values (Figure 1E). Conclusion The GEPII-technique is an easy to use, reliable and suitable method for salivary K+ determination in healthy individuals and in HD patients with accuracy and precision comparable to that of ISE. Despite heterogeneous baselines, changes of [K+]saliva represent a sensitive marker of K+ derangements as well as hyper- and normokalemia in HD patients. Although we observed that [K+] saliva dynamically follows [K+]plasma , an exact quantification - most likely due to the low number of cases per HD sessions in this pilot-study – was not possible. Additionally, how closely [K+] saliva tracks [K+]plasma in patien ts with hypokalemia was not addressed in this study. To confidently answer whether [K+]saliva measurement can potentially be used in the care of patients at increased risk of hyperkalemia, further studies in a larger number of patients need to be conducted.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. 3 ( 2023-02-28), p. 757-763
    Abstract: Hyperkalemia is a common complication in cardiorenal patients treated with agents interfering with renal potassium (K+) excretion. It frequently leads to discontinuation of potentially life-saving medication, which has increased the importance of K+ monitoring. Non-invasive means to detect hyperkalemia are currently unavailable, but would be of potential use for therapy guidance. The aim of the present study was to assess the analytical performance of genetically encoded potassium-ion indicators (GEPIIs) in measuring salivary [K+] ([K+] Saliva) and to determine whether changes of [K+]Saliva depict those of [K+] Plasma. Methods We conducted this proof-of-concept study: saliva samples from 20 healthy volunteers as well as plasma and saliva from 29 patients on hemodialysis (HD) before and after three consecutive HD treatments were collected. We compared [K+]Saliva as assessed by the gold standard ion-selective electrode (ISE) with GEPII measurements. Results The Bland–Altmann analysis showed a strong agreement (bias 0.71; 95% limits of agreement from –2.79 to 4.40) between GEPII and ISE. Before treatment, patients on HD showed significantly higher [K+]Saliva compared with healthy controls [median 37.7 (30.85; 48.46) vs 23.8 (21.63; 25.23) mmol/L; P  & lt; .05]. [K+] Plasma in HD patients decreased significantly after dialysis. This was paralleled by a significant decrease in [K+]Saliva, and both parameters increased until the subsequent HD session. Despite similar kinetics, we found weak or no correlation between [K+] Plasma and [K+]Saliva. Conclusion GEPIIs have shown an excellent performance in determining [K+]Saliva. [K+] Plasma and [K+]Saliva exhibited similar kinetics. To determine whether saliva could be a suitable sample type to monitor [K+] Plasma, further testing in future studies are required.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 4
    In: The American Journal of Pathology, Elsevier BV, Vol. 178, No. 5 ( 2011-05), p. 1999-2006
    Type of Medium: Online Resource
    ISSN: 0002-9440
    RVK:
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 1480207-7
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  • 5
    In: Diabetes, American Diabetes Association, Vol. 60, No. 11 ( 2011-11-01), p. 2954-2962
    Abstract: To assess the potential role of FoxP3-expressing regulatory T cells (Tregs) in reversing obesity-linked insulin resistance and diabetic nephropathy in rodent models and humans. RESEARCH DESIGN AND METHODS To characterize the role of Tregs in insulin resistance, human visceral adipose tissue was first evaluated for Treg infiltration and second, the db/db mouse model was evaluated. RESULTS Obese patients with insulin resistance displayed significantly decreased natural Tregs but an increase in adaptive Tregs in their visceral adipose tissue as compared with lean control subjects. To further evaluate the pathogenic role of Tregs in insulin resistance, the db/db mouse model was used. Treg depletion using an anti-CD25 monoclonal antibody enhanced insulin resistance as shown by increased fasting blood glucose levels as well as an impaired insulin sensitivity. Moreover, Treg-depleted db/db mice developed increased signs of diabetic nephropathy, such as albuminuria and glomerular hyperfiltration. This was paralleled by a proinflammatory milieu in both murine visceral adipose tissue and the kidney. Conversely, adoptive transfer of CD4+FoxP3+ Tregs significantly improved insulin sensitivity and diabetic nephropathy. Accordingly, there was increased mRNA expression of FoxP3 as well as less abundant proinflammatory CD8+CD69+ T cells in visceral adipose tissue and kidneys of Treg-treated animals. CONCLUSIONS Data suggest a potential therapeutic value of Tregs to improve insulin resistance and end organ damage in type 2 diabetes by limiting the proinflammatory milieu.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2011
    detail.hit.zdb_id: 1501252-9
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