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Article ; Online: Case report of progressive renal dysfunction as a consequence of amiodarone-induced phospholipidosis.

Duineveld, Mirjam D / Kers, Jesper / Vleming, Louis-Jean

European heart journal. Case reports

2023 Volume 7, Issue 9, Page(s) ytad457

Abstract: Background: Amiodarone is associated with a range of unwanted effects on pulmonary, thyroid, and liver function. However, the nephrotoxic side effect caused by renal phospholipidosis has hardly received any attention up to now.: Case summary: This is ...

Abstract	Background: Amiodarone is associated with a range of unwanted effects on pulmonary, thyroid, and liver function. However, the nephrotoxic side effect caused by renal phospholipidosis has hardly received any attention up to now. Case summary: This is a case of an 86-year-old Caucasian male with an acute on chronic kidney disease 4 months after the initiation of amiodarone. A renal biopsy demonstrated the intracellular accumulation of phospholipids that have previously been demonstrated in association with organ dysfunction because of amiodarone use. Serum creatinine levels subsequently improved from 388 to 314 µmol/L after stopping amiodarone over the course of 2 months. Discussion: In this case, a diagnosis of partially reversible acute on chronic kidney disease caused by lysosomal phospholipidosis due to amiodarone use was deemed highly likely. Lysosomal dysfunction leads to the accumulation of intra-lysosomal phospholipids (phospholipidosis). This accumulation is accompanied by progressive organ damage and dysfunction, including renal dysfunction, in rare instances. Guidelines advise regular surveillance for liver, lung, and thyroid toxicity during amiodarone treatment but do not mention the potential for renal toxicity. This case suggests that it might be prudent to include screening for renal toxicity in this surveillance.
Language	English
Publishing date	2023-09-14
Publishing country	England
Document type	Case Reports
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytad457
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Article ; Online: Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells.

du Long, Romy / Florquin, Sandrine / Kers, Jesper

Journal of the American Society of Nephrology : JASN

2022 Volume 33, Issue 4, Page(s) 867

MeSH term(s)	B-Lymphocytes ; Biopsy ; Graft Rejection/pathology ; Kidney/pathology ; Kidney Transplantation ; Lymphoid Tissue
Language	English
Publishing date	2022-02-03
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2021111509
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Zs.A 3344: Show issues

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Article ; Online: Multistain segmentation of renal histology: first steps toward artificial intelligence-augmented digital nephropathology.

Bülow, Roman D / Kers, Jesper / Boor, Peter

Kidney international

2021 Volume 99, Issue 1, Page(s) 17–19

Abstract: Artificial intelligence (AI), and particularly deep learning (DL), are showing great potential in improving pathology diagnostics in many aspects, 1 of which is the segmentation of histology into (diagnostically) relevant compartments. Although most ... ...

Abstract	Artificial intelligence (AI), and particularly deep learning (DL), are showing great potential in improving pathology diagnostics in many aspects, 1 of which is the segmentation of histology into (diagnostically) relevant compartments. Although most current studies focus on AI and DL in oncologic pathology, an increasing number of studies explore their application to nephropathology, including the study published in this issue of Kidney International by Jayapandian et al.
MeSH term(s)	Artificial Intelligence ; Coloring Agents ; Deep Learning ; Kidney ; Kidney Cortex
Chemical Substances	Coloring Agents
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2020.08.025
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Zs.A 797: Show issues

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Article ; Online: Evaluation of Fast and Sensitive Proteome Profiling of FF and FFPE Kidney Patient Tissues.

Dapic, Irena / Uwugiaren, Naomi / Kers, Jesper / Mohammed, Yassene / Goodlett, David R / Corthals, Garry

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 3

Abstract: The application of proteomics to fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) human tissues is an important development spurred on by requests from stakeholder groups in clinical fields. One objective is to complement current diagnostic ... ...

Abstract	The application of proteomics to fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) human tissues is an important development spurred on by requests from stakeholder groups in clinical fields. One objective is to complement current diagnostic methods with new specific molecular information. An important goal is to achieve adequate and consistent protein recovery across and within large-scale studies. Here, we describe development of several protocols incorporating mass spectrometry compatible detergents, including Rapigest, PPS, and ProteaseMax. Methods were applied on 4 and 15 μm thick FF tissues, and 4 μm thick FFPE tissues. We evaluated sensitivity and repeatability of the methods and found that the protocol containing Rapigest enabled detection of 630 proteins from FF tissue of 1 mm
MeSH term(s)	Formaldehyde ; Humans ; Kidney/chemistry ; Mass Spectrometry ; Paraffin Embedding ; Proteome/analysis ; Proteomics ; Tissue Fixation
Chemical Substances	Proteome ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2022-02-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27031137
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Zs.MO 81: Show issues

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Article ; Online: Renal biopsies from donors with acute kidney injury show different molecular patterns according to the post-transplant function.

Neri, Flavia / Lo Faro, Maria Letizia / Kaisar, Maria / Tam, Ka Ho / Borak, Martyna / Lindeman, Jan / Angelini, Annalisa / Fedrigo, Marny / Kers, Jesper / Hunter, James / Ploeg, Rutger

Scientific reports

2024 Volume 14, Issue 1, Page(s) 6643

Abstract: The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty ... ...

Abstract	The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty kidney biopsies from donors with (20) and without AKI (20) were selected and then subdivided according to the post-transplant outcome defined as a threshold of 45 ml/min for the eGFR at 1 year from transplantation. Tissue homogenates were analysed by western blot to assess how the levels of 17 pre-selected proteins varied across the four groups. Samples from AKI kidneys with a poor outcome showed a fourfold increase in the levels of PPARg and twofold reduction of STAT1 compared to the other groups (p < 0.05). On the contrary, antioxidant enzymes including TRX1 and PRX3 were increased in the AKI kidneys with a good outcome (p < 0.05). An opposite trend was observed for the detoxifying enzyme GSTp which was significantly increased in the AKI group with poor versus good outcome (p < 0.05). The importance of lipid metabolism (PPARg) and inflammatory signals (STAT1) in the function recovery of these kidneys hints to the therapeutical targeting of the involved pathways in the setting of organ reconditioning.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; PPAR gamma ; Graft Survival ; Tissue Donors ; Kidney/pathology ; Acute Kidney Injury/pathology ; Biopsy ; Retrospective Studies
Chemical Substances	PPAR gamma
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56277-x
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Article ; Online: Metabolic Flexibility and Innate Immunity in Renal Ischemia Reperfusion Injury: The Fine Balance Between Adaptive Repair and Tissue Degeneration.

Tammaro, Alessandra / Kers, Jesper / Scantlebery, Angelique M L / Florquin, Sandrine

Frontiers in immunology

2020 Volume 11, Page(s) 1346

Abstract: Renal ischemia reperfusion injury (IRI), a common event after renal transplantation, causes acute kidney injury (AKI), increases the risk of delayed graft function (DGF), primes the donor kidney for rejection, and contributes to the long-term risk of ... ...

Abstract	Renal ischemia reperfusion injury (IRI), a common event after renal transplantation, causes acute kidney injury (AKI), increases the risk of delayed graft function (DGF), primes the donor kidney for rejection, and contributes to the long-term risk of graft loss. In the last decade, epidemiological studies have linked even mild episodes of AKI to chronic kidney disease (CKD) progression, and innate immunity seems to play a crucial role. The ischemic insult triggers an acute inflammatory reaction that is elicited by Pattern Recognition Receptors (PRRs), expressed on both infiltrating immune cells as well as tubular epithelial cells (TECs). Among the PRRs, Toll-like receptors (TLRs), their synergistic receptors, Nod-like receptors (NLRs), and the inflammasomes, play a pivotal role in shaping inflammation and TEC repair, in response to renal IRI. These receptors represent promising targets to modulate the extent of inflammation, but also function as gatekeepers of tissue repair, protecting against AKI-to-CKD progression. Despite the important considerations on timely use of therapeutics, in the context of IRI, treatment options are limited by a lack of understanding of the intra- and intercellular mechanisms associated with the activation of innate immune receptors and their impact on adaptive tubular repair. Accumulating evidence suggests that TEC-associated innate immunity shapes the tubular response to stress through the regulation of immunometabolism. Engagement of innate immune receptors provides TECs with the metabolic flexibility necessary for their plasticity during injury and repair. This could significantly affect pathogenic processes within TECs, such as cell death, mitochondrial damage, senescence, and pro-fibrotic cytokine secretion, well-known to exacerbate inflammation and fibrosis. This article provides an overview of the past 5 years of research on the role of innate immunity in experimental and human IRI, with a focus on the cascade of events activated by hypoxic damage in TECs: from programmed cell death (PCD) and mitochondrial dysfunction-mediated metabolic rewiring of TECs to maladaptive repair and progression to fibrosis. Finally, we will discuss the important crosstalk between metabolism and innate immunity observed in TECs and their therapeutic potential in both experimental and clinical research.
MeSH term(s)	Acute Kidney Injury/etiology ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Animals ; Apoptosis ; Cellular Senescence ; Computational Biology/methods ; Disease Progression ; Energy Metabolism ; Humans ; Immunity, Innate ; Kidney Transplantation ; Kidney Tubules/immunology ; Kidney Tubules/metabolism ; Kidney Tubules/pathology ; Ligands ; Mitochondria/genetics ; Mitochondria/immunology ; Mitochondria/metabolism ; Receptors, Pattern Recognition/metabolism ; Reperfusion Injury/etiology ; Reperfusion Injury/metabolism ; Reperfusion Injury/pathology ; Wound Healing
Chemical Substances	Ligands ; Receptors, Pattern Recognition
Language	English
Publishing date	2020-07-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01346
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Article ; Online: Generation of Alloreactive-Anergized Tr1 Cells From Patients on Dialysis for the Induction of Renal Transplant Tolerance: Are We There Yet?

Kers, Jesper / Florquin, Sandrine

Transplantation

2015 Volume 99, Issue 8, Page(s) 1551–1552

MeSH term(s)	Female ; Humans ; Immune Tolerance ; Kidney Failure, Chronic/therapy ; Kidney Transplantation ; Male ; Renal Dialysis ; T-Lymphocytes, Regulatory/immunology ; Waiting Lists
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000000752
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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: Antineutrophil cytoplasmic antibodies in infective endocarditis: a case report and systematic review of the literature.

Van Gool, Inge C / Kers, Jesper / Bakker, Jaap A / Rotmans, Joris I / Teng, Y K Onno / Bauer, Martijn P

Clinical rheumatology

2022 Volume 41, Issue 10, Page(s) 2949–2960

Abstract: Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA ... ...

Abstract	Infective endocarditis (IE) may be misdiagnosed as ANCA-associated vasculitis (AAV), especially when antineutrophil cytoplasmic antibodies (ANCA) are detected. Distinguishing IE from AAV is crucial to guide therapy. However, little is known about ANCA positivity in IE patients. We present a case report and systematic review of the literature on patients with ANCA-positive IE, aiming to provide a comprehensive overview of this entity and to aid clinicians in their decisions when encountering a similar case. A systematic review of papers on original cases of ANCA-positive IE without a previous diagnosis of AAV was conducted on PubMed in accordance with PRISMA-IPD guidelines. A predefined set of clinical, laboratory, and kidney biopsy findings was extracted for each patient and presented as a narrative and quantitative synthesis. A total of 74 reports describing 181 patients with ANCA-positive IE were included (a total of 182 cases including our own case). ANCA positivity was found in 18-43% of patients with IE. Patients usually presented with subacute IE (73%) and had positive cytoplasmic ANCA-staining or anti-proteinase-3 antibodies (79%). Kidney function was impaired in 72%; kidney biopsy findings were suggestive of immune complexes in 59%, while showing pauci-immune glomerulonephritis in 37%. All were treated with antibiotics; 39% of patients also received immunosuppressants. During follow-up, 69% of patients became ANCA-negative and no diagnosis of systemic vasculitis was reported. This study reviewed the largest series of patients with ANCA-positive IE thus far and shows the overlap in clinical manifestations between IE and AAV. We therefore emphasize that clinicians should be alert to the possibility of an underlying infection when treating a patient with suspected AAV, even when reassured by ANCA positivity. Key Points • This systematic review describes - to our knowledge - the largest series of patients with ANCA-positive infective endocarditis (IE) thus far (N=182), and shows a high degree of overlap in clinical manifestations between IE and ANCA-associated vasculitis (AAV). • ANCA positivity was found in 18-43% of patients with infective endocarditis. Of patients with ANCA-positive IE, the majority (79%) showed cytoplasmic ANCA-staining or anti-PR3-antibodies. We emphasize that clinicians should be alert to the possibility of an underlying infection when treating a patient with suspected AAV, even when reassured by ANCA positivity. • In patients with IE and ANCA-associated symptoms such as acute kidney injury, an important clinical challenge is the initiation of immunosuppressive therapy. All patients with data in this series received antibiotics; 39% also received immunosuppressive therapy. In many of these patients, ANCA-associated symptoms resolved or stabilized after infection was treated. ANCA titers became negative in 69% , and a diagnosis of AAV was made in none of the cases. We therefore recommend that (empiric) antibiotic treatment remains the therapeutic cornerstone for ANCA-positive IE patients, while a watchful wait-and-see approach with respect to immunosuppression is advised.
MeSH term(s)	Anti-Bacterial Agents ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications ; Antibodies, Antineutrophil Cytoplasmic ; Antigen-Antibody Complex ; Endocarditis ; Humans ; Immunosuppressive Agents/therapeutic use
Chemical Substances	Anti-Bacterial Agents ; Antibodies, Antineutrophil Cytoplasmic ; Antigen-Antibody Complex ; Immunosuppressive Agents
Language	English
Publishing date	2022-06-23
Publishing country	Germany
Document type	Case Reports ; Journal Article ; Review ; Systematic Review
ZDB-ID	604755-5
ISSN	1434-9949 ; 0770-3198
ISSN (online)	1434-9949
ISSN	0770-3198
DOI	10.1007/s10067-022-06240-w
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Zs.A 1740: Show issues

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Article ; Online: Immune reconstitution inflammatory syndrome induced by gluteal silicones in a transgender woman living with HIV.

van der Pluijm, Rob W / W Haak, Bastiaan / Kers, Jesper / L Siegenbeek van Heukelom, Thijs / van Vugt, Michele

International journal of STD & AIDS

2022 Volume 33, Issue 6, Page(s) 625–627

Abstract: We report a case of an immune reconstitution inflammatory syndrome induced by gluteal silicones in a transgender woman living with HIV following the start of antiretroviral therapy. This case resembles the autoimmune/inflammatory syndrome induced by ... ...

Abstract	We report a case of an immune reconstitution inflammatory syndrome induced by gluteal silicones in a transgender woman living with HIV following the start of antiretroviral therapy. This case resembles the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) syndrome that has been described as a complication of insertions of materials such as injected or implanted silicones. The potential of developing an inflammatory response in patient with injected or implanted silicones/foreign substances should be considered in patients who have recently started antiretroviral therapy.
MeSH term(s)	Adjuvants, Immunologic ; Female ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Immune Reconstitution Inflammatory Syndrome/complications ; Silicones ; Transgender Persons
Chemical Substances	Adjuvants, Immunologic ; Silicones
Language	English
Publishing date	2022-03-26
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1018089-8
ISSN	1758-1052 ; 0956-4624
ISSN (online)	1758-1052
ISSN	0956-4624
DOI	10.1177/09564624221086853
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Zs.A 2829: Show issues

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Article: Renal amyloidosis: validation of a proposed histological scoring system in an independent cohort.

Hoelbeek, Joris J / Kers, Jesper / Steenbergen, Eric J / Roelofs, Joris J T H / Florquin, Sandrine

Clinical kidney journal

2020 Volume 14, Issue 3, Page(s) 855–862

Abstract: Background: In systemic amyloidosis, the kidney is frequently affected and renal involvement has a major impact on survival. Renal involvement is clinically characterized by decreased estimated glomerular filtration rate (eGFR) and proteinuria. The two ... ...

Abstract	Background: In systemic amyloidosis, the kidney is frequently affected and renal involvement has a major impact on survival. Renal involvement is clinically characterized by decreased estimated glomerular filtration rate (eGFR) and proteinuria. The two most common renal amyloidosis types are light chain-related amyloidosis (AL) and serum amyloid A (AA) amyloidosis. Standardized histopathological scoring of amyloid deposits is crucial to assess disease progression. Therefore, we aimed to validate the proposed scoring system from Rubinstein Methods: We attempt to reproduce the scoring system, consisting of an amyloid score (AS) and a composite scarring injury score (CSIS), in a multicentre AL and AA case series. Additionally, we analysed all renal amyloidosis kidney biopsies performed in the Netherlands between 1993 and 2012. Results: Similar to the original study, AS and CSIS correlated to eGFR ( Conclusions: In our AL case series and the original study, AS and CSIS were correlated to eGFR but not to proteinuria, and AS correlated with renal outcome. Overall, we regard this scoring system as competent for standardized histopathological assessment of amyloid deposits burden and thereby disease advancement in renal biopsies.
Language	English
Publishing date	2020-03-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfaa019
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Zs.A 6587: Show issues

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