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Article ; Online: Memory B-cell derived donor-specific antibodies do not predict outcome in sensitized kidney transplant recipients: a retrospective single-center study.

Altulea, Dania / van den Born, Joost C / Diepstra, Arjan / Bungener, Laura / Terpstra, Dagmar / Hepkema, Bouke G / Lammerts, Rosa / Heeringa, Peter / Heidt, Sebastiaan / Otten, Henny / Reteig, Leon / Karahan, Gonca E / Berger, Stefan P / Sanders, Jan-Stephan

Frontiers in immunology

2024 Volume 15, Page(s) 1360627

Abstract: Background: Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant ... ...

Abstract	Background: Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant recipients (KTRs). This single-center retrospective study aimed to identify DSAm and assess their association with outcomes in a cohort of KTRs with pretransplant serum donor-specific antibodies (DSA). Methods: We polyclonally activated pretransplant peripheral blood mononuclear cells (PBMCs) from 60 KTRs in vitro, isolated and quantified IgG from the culture supernatant using ELISA, and analyzed the HLA antibodies of eluates with single antigen bead (SAB) assays, comparing them to the donor HLA typing for potential DSAm. Biopsies from 41 KTRs were evaluated for rejection based on BANFF 2019 criteria. Results: At transplantation, a total of 37 DSAm were detected in 26 of 60 patients (43%), of which 13 (35%) were found to be undetectable in serum. No significant association was found between pretransplant DSAm and ABMR (P=0.53). Similar results were observed in a Kaplan-Meier analysis for ABMR within the first year posttransplant (P=0.29). Additionally, MFI levels of DSAm showed no significant association with ABMR (P=0.28). Conclusion: This study suggests no significant association between DSAm and biopsy-proven clinical ABMR. Further prospective research is needed to determine whether assessing DSAm could enhance existing immunological risk assessment methods for monitoring KTRs, particularly in non-sensitized KTRs.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; Retrospective Studies ; Male ; Female ; Middle Aged ; Graft Rejection/immunology ; Isoantibodies/immunology ; Isoantibodies/blood ; Adult ; HLA Antigens/immunology ; Memory B Cells/immunology ; Tissue Donors ; Aged ; Transplant Recipients ; Graft Survival/immunology
Chemical Substances	Isoantibodies ; HLA Antigens
Language	English
Publishing date	2024-04-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1360627
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Article ; Online: Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial.

van den Born, Joost C / Meziyerh, Soufian / Vart, Priya / Bakker, Stephan J L / Berger, Stefan P / Florquin, Sandrine / de Fijter, Johan W / Gomes-Neto, António W / Idu, Mirza M / Pol, Robert A / Roelen, Dave L / van Sandwijk, Marit S / de Vries, Dorottya K / de Vries, Aiko P J / Bemelman, Frederike J / Sanders, Jan Stephan F

Transplantation

2024 Volume 108, Issue 2, Page(s) 556–566

Abstract: Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.: Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open- ... ...

Abstract	Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. Results: A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m 2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m 2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m 2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection ( P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. Conclusions: Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
MeSH term(s)	Humans ; Tacrolimus/adverse effects ; Kidney Transplantation/adverse effects ; Immunosuppressive Agents/adverse effects ; Immunosuppression Therapy ; Mycophenolic Acid/adverse effects ; Steroids ; Graft Rejection/prevention & control ; Carbazoles ; Tryptamines
Chemical Substances	Tacrolimus (WM0HAQ4WNM) ; frovatriptan (H82Q2D5WA7) ; Immunosuppressive Agents ; Mycophenolic Acid (HU9DX48N0T) ; Steroids ; Carbazoles ; Tryptamines
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Randomized Controlled Trial ; Multicenter Study ; Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004776
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Zs.A 488: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 509: Show issues

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Article ; Online: Hydrogen sulfide in hypertension.

van Goor, Harry / van den Born, Joost C / Hillebrands, Jan-Luuk / Joles, Jaap A

Current opinion in nephrology and hypertension

2016 Volume 25, Issue 2, Page(s) 107–113

Abstract: Purpose of review: Hypertension is an important determinant of cardiovascular disease, and strict blood pressure regulation is beneficially associated with the risk for cardiovascular events or all-cause mortality. However, intensive antihypertensive ... ...

Abstract	Purpose of review: Hypertension is an important determinant of cardiovascular disease, and strict blood pressure regulation is beneficially associated with the risk for cardiovascular events or all-cause mortality. However, intensive antihypertensive treatment is not always sufficient to reach normotension. Hydrogen sulfide (H2S) is a gaseous signalling molecule with antihypertensive properties. It is endogenously produced, but can also be exogenously administrated. The current review provides an overview on H2S research performed in the context of hypertension and cardiovascular disease. Recent findings: H2S has been increasingly found to contribute to different (patho-)physiological processes such as blood pressure regulation and scavenging of reactive oxygen species. A deficiency of H2S-producing enzymes results in hypertension, and administration of H2S donors lowers blood pressure and protects against organ damage in the experimental setting. Thiosulfate, a H2S metabolite, can act as a H2S donor, and is already clinically used for the treatment of calciphylaxis in patients with end-stage renal disease. Treatment of hypertensive rats with thiosulfate results in lower blood pressure and reduces organ damage. Summary: Although human data on H2S and hypertension are scarce, experimental data indicate that elevation of H2S levels using dietary sulfate or exogenous H2S (donors) could be a promising therapeutic strategy in the setting of hypertension.
MeSH term(s)	Animals ; Antihypertensive Agents/therapeutic use ; Blood Pressure/drug effects ; Humans ; Hydrogen Sulfide/metabolism ; Hydrogen Sulfide/pharmacology ; Hydrogen Sulfide/therapeutic use ; Hypertension/drug therapy ; Hypertension/metabolism ; Thiosulfates/therapeutic use
Chemical Substances	Antihypertensive Agents ; Thiosulfates ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000206
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Zs.A 3686: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Gasotransmitters in Vascular Complications of Diabetes.

van den Born, Joost C / Hammes, Hans-Peter / Greffrath, Wolfgang / van Goor, Harry / Hillebrands, Jan-Luuk

Diabetes

2016 Volume 65, Issue 2, Page(s) 331–345

Abstract: In the past decades three gaseous signaling molecules-so-called gasotransmitters-have been identified: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These gasotransmitters are endogenously produced by different enzymes in various ... ...

Abstract	In the past decades three gaseous signaling molecules-so-called gasotransmitters-have been identified: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These gasotransmitters are endogenously produced by different enzymes in various cell types and play an important role in physiology and disease. Despite their specific functions, all gasotransmitters share the capacity to reduce oxidative stress, induce angiogenesis, and promote vasorelaxation. In patients with diabetes, a lower bioavailability of the different gasotransmitters is observed when compared with healthy individuals. As yet, it is unknown whether this reduction precedes or results from diabetes. The increased risk for vascular disease in patients with diabetes, in combination with the extensive clinical, financial, and societal burden, calls for action to either prevent or improve the treatment of vascular complications. In this Perspective, we present a concise overview of the current data on the bioavailability of gasotransmitters in diabetes and their potential role in the development and progression of diabetes-associated microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (cerebrovascular, coronary artery, and peripheral arterial diseases) complications. Gasotransmitters appear to have both inhibitory and stimulatory effects in the course of vascular disease development. This Perspective concludes with a discussion on gasotransmitter-based interventions as a therapeutic option.
MeSH term(s)	Biological Availability ; Carbon Monoxide/physiology ; Diabetes Mellitus/physiopathology ; Diabetic Angiopathies/etiology ; Diabetic Angiopathies/physiopathology ; Gasotransmitters/physiology ; Humans ; Hydrogen Sulfide/metabolism ; Neovascularization, Pathologic/etiology ; Nitric Oxide/physiology ; Oxidative Stress ; Vasodilation
Chemical Substances	Gasotransmitters ; Nitric Oxide (31C4KY9ESH) ; Carbon Monoxide (7U1EE4V452) ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db15-1003
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Uh III Zs.175: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Urinary Excretion of Sulfur Metabolites and Risk of Cardiovascular Events and All-Cause Mortality in the General Population.

van den Born, Joost C / Frenay, Anne-Roos S / Koning, Anne M / Bachtler, Matthias / Riphagen, Ineke J / Minovíc, Isidor / Feelisch, Martin / Dekker, Marinda M / Bulthuis, Marian L C / Gansevoort, Ron T / Hillebrands, Jan-Luuk / Pasch, Andreas / Bakker, Stephan J L / van Goor, Harry

Antioxidants & redox signaling

2018 Volume 30, Issue 17, Page(s) 1999–2010

Abstract: Aims: ...

Abstract	Aims:
MeSH term(s)	Adult ; Aged ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/urine ; Cause of Death ; Disease Susceptibility ; Female ; Humans ; Male ; Metabolome ; Middle Aged ; Mortality ; Population Surveillance ; Prognosis ; Proportional Hazards Models ; Sulfates/urine ; Sulfur/metabolism ; Sulfur/urine ; Thiosulfates/urine
Chemical Substances	Sulfates ; Thiosulfates ; Sulfur (70FD1KFU70)
Language	English
Publishing date	2018-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2017.7040
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Zs.A 5488: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: High urinary sulfate concentration is associated with reduced risk of renal disease progression in type 2 diabetes.

van den Born, Joost C / Frenay, Anne-Roos S / Bakker, Stephan J L / Pasch, Andreas / Hillebrands, Jan-Luuk / Lambers Heerspink, Hiddo J / van Goor, Harry

Nitric oxide : biology and chemistry

2016 Volume 55-56, Page(s) 18–24

Abstract: Diabetes is associated with a high incidence of microvascular disease, including nephropathy. Diabetic nephropathy is the most common cause of chronic kidney disease in the Western world. Sulfate in the urine is the metabolic end product of hydrogen ... ...

Abstract	Diabetes is associated with a high incidence of microvascular disease, including nephropathy. Diabetic nephropathy is the most common cause of chronic kidney disease in the Western world. Sulfate in the urine is the metabolic end product of hydrogen sulfide (H2S), a recent discovered gaseous signaling molecule. Urinary sulfate has earlier shown beneficial predictive properties in renal transplant recipients. Based on the protective role of exogenous H2S in experimental models of diabetic nephropathy, we aimed to cross-sectionally investigate the association of sulfate with renal risk markers, and to prospectively investigate its predictive value for renal events in patients with diabetic nephropathy. Post-hoc analysis on data of the sulodexide macroalbuminuria (Sun-MACRO) trial and the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study was performed. A total of 1004 patients with type 2 diabetes were included. Urinary sulfate concentration was measured and cross-sectionally associated to renal risk markers by linear regression. Multivariable Cox regression analysis was performed to assess the prospective association of sulfate with renal events, which was defined as end stage renal disease or a doubling of baseline serum creatinine. Mean age was 63 ± 9 years, median sulfate concentration was 8.0 (IQR 5.8-11.4) mmol/L. Urinary sulfate positively associated with male gender, hemoglobin, and negatively associated with albuminuria at baseline. During follow-up for 12 (IQR 6-18) months, 38 renal events occurred. Each doubling of urinary sulfate was associated with a 19% (95%CI 1%-34%) lower risk of renal events, independent of adjustment for potential confounders, including age, estimated glomerular filtration rate (eGFR), and albuminuria. To conclude, higher urinary sulfate concentration is associated with a more beneficial profile of renal risk markers, and is independently associated with a reduced risk for renal events in type 2 diabetes patients with nephropathy.
Language	English
Publishing date	2016-05-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1362794-6
ISSN	1089-8611 ; 1089-8603
ISSN (online)	1089-8611
ISSN	1089-8603
DOI	10.1016/j.niox.2016.03.001
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Zs.A 4677: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.

Snijder, Pauline M / de Boer, Rudolf A / Bos, Eelke M / van den Born, Joost C / Ruifrok, Willem-Peter T / Vreeswijk-Baudoin, Inge / van Dijk, Marcory C R F / Hillebrands, Jan-Luuk / Leuvenink, Henri G D / van Goor, Harry

PloS one

2013 Volume 8, Issue 5, Page(s) e63291

Abstract: Background: Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S) is protective during IRI by inducing a hypometabolic state in mice which is associated with anti- ... ...

Abstract	Background: Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S) is protective during IRI by inducing a hypometabolic state in mice which is associated with anti-apoptotic, anti-inflammatory and antioxidant properties. We investigated whether gaseous H2S administration is protective in cardiac IRI and whether non-hypometabolic concentrations of H2S have similar protective properties. Methods: Male C57BL/6 mice received a 0, 10, or 100 ppm H2S-N2 mixture starting 30 minutes prior to ischemia until 5 minutes pre-reperfusion. IRI was inflicted by temporary ligation of the left coronary artery for 30 minutes. High-resolution respirometry equipment was used to assess CO2-production and blood pressure was measured using internal transmitters. The effects of H2S were assessed by histological and molecular analysis. Results: Treatment with 100 ppm H2S decreased CO2-production by 72%, blood pressure by 14% and heart rate by 25%, while treatment with 10 ppm H2S had no effects. At day 1 of reperfusion 10 ppm H2S showed no effect on necrosis, while treatment with 100 ppm H2S reduced necrosis by 62% (p<0.05). Seven days post-reperfusion, both 10 ppm (p<0.01) and 100 ppm (p<0.05) H2S showed a reduction in fibrosis compared to IRI animals. Both 10 ppm and 100 ppm H2S reduced granulocyte-influx by 43% (p<0.05) and 60% (p<0.001), respectively. At 7 days post-reperfusion both 10 and 100 ppm H2S reduced expression of fibronectin by 63% (p<0.05) and 67% (p<0.01) and ANP by 84% and 63% (p<0.05), respectively. Conclusions: Gaseous administration of H2S is protective when administered during a cardiac ischemic insult. Although hypometabolism is restricted to small animals, we now showed that low non-hypometabolic concentrations of H2S also have protective properties in IRI. Since IRI is a frequent cause of myocardial damage during percutaneous coronary intervention and cardiac transplantation, H2S treatment might lead to novel therapeutical modalities.
MeSH term(s)	Animals ; Atrial Natriuretic Factor/genetics ; Blood Pressure/drug effects ; Carbon Dioxide/metabolism ; Cell Line ; Disease Models, Animal ; Gene Expression ; Heart Rate/drug effects ; Hydrogen Sulfide/administration & dosage ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/pathology ; Male ; Membrane Glycoproteins/genetics ; Mice ; Myoblasts, Cardiac/drug effects ; Myoblasts, Cardiac/metabolism ; Myocardial Reperfusion Injury/genetics ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/prevention & control ; Myocardium/metabolism ; Myocardium/pathology ; NADPH Oxidase 2 ; NADPH Oxidase 4 ; NADPH Oxidases/genetics ; Oxidative Stress/drug effects ; Rats
Chemical Substances	Membrane Glycoproteins ; Carbon Dioxide (142M471B3J) ; Atrial Natriuretic Factor (85637-73-6) ; Cybb protein, mouse (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-) ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2013-05-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0063291
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Article ; Online: Memory B-cell derived donor-specific antibodies do not predict outcome in sensitized kidney transplant recipients: a retrospective single-center study.

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Article ; Online: Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial.

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Article ; Online: Hydrogen sulfide in hypertension.

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Article ; Online: Gasotransmitters in Vascular Complications of Diabetes.

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Article ; Online: Urinary Excretion of Sulfur Metabolites and Risk of Cardiovascular Events and All-Cause Mortality in the General Population.

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Article ; Online: High urinary sulfate concentration is associated with reduced risk of renal disease progression in type 2 diabetes.

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Article ; Online: Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.

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