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Article ; Online: Disease Recurrence-The Sword of Damocles in Kidney Transplantation for Primary Focal Segmental Glomerulosclerosis.

Kienzl-Wagner, Katrin / Waldegger, Siegfried / Schneeberger, Stefan

2019 Volume 10, Page(s) 1669

Abstract: A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to ...

Abstract	A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell depleting antibodies are effective in recurrent FSGS. This indicates, that the secretion and/or activity of the postulated circulating permeability factor(s) may be B-cell related. This review summarizes the current knowledge on permeability factor(s) possibly related to the disease and discusses strategies for the management of recurrent FSGS. These include profound B-cell depletion prior to transplantation, as well as the salvage of an allograft affected by recurrent FSGS by transfer into a second recipient.
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; Glomerulosclerosis, Focal Segmental/immunology ; Glomerulosclerosis, Focal Segmental/surgery ; Humans ; Kidney/immunology ; Kidney/surgery ; Kidney Transplantation/adverse effects ; Recurrence
Language	English
Publishing date	2019-07-17
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.2019.01669
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Article: Heartburn: cardiac potassium channels involved in parietal cell acid secretion.

Waldegger, Siegfried

Pflugers Archiv : European journal of physiology

2003 Volume 446, Issue 2, Page(s) 143–147

Abstract: Hydrochloric acid is produced in parietal cells of the gastric glands by an H(+)/K(+)-ATPase. This proton pump couples the outwards movement of H(+) to the inwards movement of K(+) thus requiring the presence of luminal K(+) to operate. To maintain the ... ...

Abstract	Hydrochloric acid is produced in parietal cells of the gastric glands by an H(+)/K(+)-ATPase. This proton pump couples the outwards movement of H(+) to the inwards movement of K(+) thus requiring the presence of luminal K(+) to operate. To maintain the activity of the pump, K(+) recirculates over the apical membrane via conductive pathways, the molecular nature of which has been identified in the past few years. This review gives a short overview about the recent advances in the understanding of the role of K(+) channels in the process of parietal cell H(+) secretion and focuses on the identification of KCNQ1/KCNE2 K(+) channel as the molecular correlate of the parietal cell apical potassium conductance.
MeSH term(s)	Animals ; Heartburn/metabolism ; Humans ; KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; Parietal Cells, Gastric/metabolism ; Parietal Cells, Gastric/secretion ; Potassium Channels/metabolism ; Potassium Channels/secretion ; Potassium Channels, Voltage-Gated
Chemical Substances	KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; KCNQ1 protein, human ; Potassium Channels ; Potassium Channels, Voltage-Gated
Language	English
Publishing date	2003-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-003-1048-5
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Article ; Online: De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus.

Cortina, Gerard / Trojer, Raphaela / Waldegger, Siegfried / Schneeberger, Stefan / Gut, Nadezda / Hofer, Johannes

Pediatric nephrology (Berlin, Germany)

2015 Volume 30, Issue 4, Page(s) 693–697

Abstract: Background: Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA) is a rare complication after renal transplantation. It may be difficult to distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its clinical ... ...

Abstract	Background: Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA) is a rare complication after renal transplantation. It may be difficult to distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its clinical presentation may vary from isolated localised forms up to catastrophic systemic presentations. Case: We report a case of tacrolimus-induced TMA soon after renal transplantation in an 11-year-old boy who received his second renal transplantation. His first graft was lost because of AMR. On day 12 after his second renal transplantation, his renal function started worsening and a kidney biopsy was performed, which showed histopathological signs of TMA. The diagnosis of tacrolimus-induced TMA was established after excluding AMR and other causes of de novo TMA. Genetic complement investigation disclosed two complement factor H risk polymorphisms as possible modifiers of TMA emergence. Treatment was based on replacing tacrolimus with everolimus, with a subsequent normalisation of renal function. Conclusion: A prompt diagnosis of de novo TMA by early allograft biopsy is essential for the allograft outcome and genetic investigations for possible complement abnormalities are reasonable, not only for patients with a systemic aspect of their post-transplant TMA. Replacing tacrolimus with everolimus effectively controlled the TMA and stabilised renal function in our patient.
MeSH term(s)	Calcineurin Inhibitors/adverse effects ; Child ; Drug Substitution ; Everolimus/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation ; Male ; Tacrolimus/adverse effects ; Thrombotic Microangiopathies/chemically induced ; Thrombotic Microangiopathies/diagnosis
Chemical Substances	Calcineurin Inhibitors ; Immunosuppressive Agents ; Everolimus (9HW64Q8G6G) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2015-04
Publishing country	Germany
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-014-3036-8
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Zs.A 2196: Show issues

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Article ; Online: Therapeutic plasma exchange in children: One center's experience.

Cortina, Gerard / Ojinaga, Violeta / Giner, Thomas / Riedl, Magdalena / Waldegger, Siegfried / Rosales, Alejandra / Trojer, Raphaela / Hofer, Johannes

Journal of clinical apheresis

2017 Volume 32, Issue 6, Page(s) 494–500

Abstract: Background: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this ... ...

Abstract	Background: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this study was to review the procedure in the context of clinical indications, effectiveness, and safety. Study design and methods: All TPE procedures performed at a tertiary care hospital during a 12-year period (2005-2016) were retrospectively evaluated. Results: Eighteen patients with a median age of 8.5 (0.2-17) years underwent a total of 280 TPE sessions. Eleven (61%) patients were treated for renal diseases. Three (17%) patients were diagnosed with neurological diseases, two had liver failure, and one patient each had sepsis and stem cell transplant-associated thrombotic microangiopathy. Seven patients (39%) were classified as American Society for Apheresis Category I, four (22%) as Category II, two (13%) each as Category III and IV, and two (13%) were not classified. Two patients with atypical hemolytic-uremic syndrome received TPE as long-term therapy over 2 and 5 years. All procedures were performed using the filtration technique and heparin anticoagulation. Twelve (67%) patients showed full or partial recovery after TPE, six had no response or an uncertain response. Minor adverse events occurred in 30/280 (10.6%) procedures, and one major complication (0.4%) was reported. Conclusion: TPE is a safe apheresis method in children, even when performed as a long-term therapy. Efficacy is high under selected conditions. A highly skilled and experienced staff is mandatory to ensure patient safety and efficacy.
MeSH term(s)	Adolescent ; Blood Component Removal ; Child ; Child, Preschool ; Filtration ; Heparin/therapeutic use ; Humans ; Infant ; Plasma Exchange/adverse effects ; Plasma Exchange/standards ; Remission Induction ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome
Chemical Substances	Heparin (9005-49-6)
Language	English
Publishing date	2017-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604912-6
ISSN	1098-1101 ; 0733-2459
ISSN (online)	1098-1101
ISSN	0733-2459
DOI	10.1002/jca.21547
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Zs.A 1831: Show issues

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Article ; Online: Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization.

Hou, Jianghui / Renigunta, Aparna / Yang, Jing / Waldegger, Siegfried

Proceedings of the National Academy of Sciences of the United States of America

2010 Volume 107, Issue 42, Page(s) 18010–18015

Abstract: Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant route for transepithelial chloride reabsorption that determines the ... ...

Abstract	Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant route for transepithelial chloride reabsorption that determines the extracellular NaCl content and the blood pressure. However, the molecular mechanisms underlying the paracellular chloride reabsorption in the collecting duct are not understood. Here we showed that in mouse kidney collecting duct cells, claudin-4 functioned as a Cl(-) channel. A positively charged lysine residue at position 65 of claudin-4 was critical for its anion selectivity. Claudin-4 was observed to interact with claudin-8 using several criteria. In the collecting duct cells, the assembly of claudin-4 into TJ strands required its interaction with claudin-8. Depletion of claudin-8 resulted in the loss of paracellular chloride conductance, through a mechanism involving its recruitment of claudin-4 during TJ assembly. Together, our data show that claudin-4 interacts with claudin-8 and that their association is required for the anion-selective paracellular pathway in the collecting duct, suggesting a mechanism for coupling chloride reabsorption with sodium reabsorption in the collecting duct.
MeSH term(s)	Amino Acid Sequence ; Animals ; Cell Membrane Permeability ; Chloride Channels/metabolism ; Claudin-4 ; Claudins ; Kidney Tubules, Collecting/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Membrane Proteins/physiology ; Mice ; Molecular Sequence Data ; Mutagenesis ; Protein Binding ; RNA Interference ; Sequence Homology, Amino Acid ; Tight Junctions/metabolism
Chemical Substances	Chloride Channels ; Claudin-4 ; Claudins ; Cldn4 protein, mouse ; Membrane Proteins ; claudin 8 (HJ6C19SU7L)
Language	English
Publishing date	2010-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1009399107
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Zs.A 1148: Show issues

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Article ; Online: Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study.

Suhlrie, Adriana / Hennies, Imke / Gellermann, Jutta / Büscher, Anja / Hoyer, Peter / Waldegger, Siegfried / Wygoda, Simone / Beetz, Rolf / Lange-Sperandio, Bärbel / Klaus, Günter / Konrad, Martin / Holder, Martin / Staude, Hagen / Rascher, Wolfgang / Oh, Jun / Pape, Lars / Tönshoff, Burkhard / Haffner, Dieter

Pediatric nephrology (Berlin, Germany)

2020 Volume 35, Issue 7, Page(s) 1235–1246

Abstract: Background: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare.: Methods: Twelve-month renal outcome and comorbidity were ... ...

Abstract	Background: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare. Methods: Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015. Results: At the time of diagnosis, median age was 13.7 (interquartile range 11.8-15.8) years; 86% showed WHO histology class IV, nephrotic range proteinuria was noted in 55%, and median estimated glomerular filtration rate amounted to 75 ml/min/1.73 m Conclusions: In this cohort of juvenile proliferative LN, renal outcome at 12 months was good irrespectively if patients received induction treatment with MMF or IVCYC, but glucocorticoid toxicity was very high underscoring the need for corticoid sparing protocols. Graphical abstract.
MeSH term(s)	Adolescent ; Child ; Cyclophosphamide/administration & dosage ; Cyclophosphamide/adverse effects ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/adverse effects ; Female ; Germany ; Glucocorticoids/adverse effects ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Lupus Nephritis/drug therapy ; Male ; Mycophenolic Acid/administration & dosage ; Mycophenolic Acid/adverse effects ; Prospective Studies ; Registries ; Remission Induction ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Enzyme Inhibitors ; Glucocorticoids ; Immunosuppressive Agents ; Cyclophosphamide (8N3DW7272P) ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2020-03-19
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-020-04501-x
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Book ; Online ; Thesis: Funktionelle Untersuchung der Bedeutung der Mutation G832A des CLCNKA-Promotors bei einer Patientin mit renalem Salzverlust und Taubheit

Pelken, Lutz Werner Josef [Verfasser] / Waldegger, Siegfried [Akademischer Betreuer]

2011

Author's details	Lutz Pelken. Betreuer: Siegfried Waldegger
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Cell Volume–Regulated Gene Transcription

Waldegger, Siegfried / Lang, Florian

Kidney and Blood Pressure Research

2008 Volume 21, Issue 2-4, Page(s) 241–244

Institution	Department of Physiology I, University of Tübingen, Germany
Keywords	Osmotic stress ; Metabolic control ; Gene transcription ; Organic osmolytes ; Immediate early genes ; Heat–shock response
Language	English
Publishing date	2008-11-13
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Basic Renal Research
ZDB-ID	1326018-2
ISSN	1423-0143 ; 1420-4096
ISSN (online)	1423-0143
ISSN	1420-4096
DOI	10.1159/000025865
Database	Karger publisher's database

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Zs.A 1458: Show issues

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Article ; Online: Successful management of recurrent focal segmental glomerulosclerosis.

Kienzl-Wagner, Katrin / Rosales, Alejandra / Scheidl, Stefan / Giner, Thomas / Bösmüller, Claudia / Rudnicki, Michael / Oberhuber, Rupert / Margreiter, Christian / Soleiman, Afschin / Öfner, Dietmar / Waldegger, Siegfried / Schneeberger, Stefan

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2018 Volume 18, Issue 11, Page(s) 2818–2822

Abstract: Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. ... ...

Abstract	Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Child, Preschool ; Glomerulosclerosis, Focal Segmental/surgery ; Graft Rejection/etiology ; Graft Rejection/prevention & control ; Humans ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Prognosis ; Recurrence
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; ofatumumab (M95KG522R0)
Language	English
Publishing date	2018-08-13
Publishing country	United States
Document type	Case Reports
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.14998
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Zs.A 5542: Show issues

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Article: pH dependence of extracellular calcium sensing receptor activity determined by a novel technique.

Doroszewicz, Jolanta / Waldegger, Petra / Jeck, Nikola / Seyberth, Hannsjörg / Waldegger, Siegfried

Kidney international

2005 Volume 67, Issue 1, Page(s) 187–192

Abstract: Background: Increasing evidence points to the role of the extracellular Calcium Sensing Receptor (CaSR) as a multimodal receptor responding to diverse physiologic stimuli, such as extracellular divalent and polyvalent cations, amino acids, and ionic ... ...

Abstract	Background: Increasing evidence points to the role of the extracellular Calcium Sensing Receptor (CaSR) as a multimodal receptor responding to diverse physiologic stimuli, such as extracellular divalent and polyvalent cations, amino acids, and ionic strength. Within the kidney, these stimuli converge on the CaSR to coordinate systemic calcium and water homeostasis. In this process, the impact of urinary pH changes on the activity of the CaSR has not yet been defined. We therefore performed the present study to analyze the pH sensitivity of the CaSR. Methods: To assess the activation state of the CaSR, we developed a new method based on the functional coupling between CaSR activity and gating of calcium sensitive potassium currents mediated by SK4 potassium channels. Two-electrode voltage clamping was used to determine whole cell currents in Xenopus oocytes heterologously expressing rat CaSR and rat SK4 potassium channels. Results: Coexpression of CaSR and SK4 gave rise to potassium currents that were dependent on CaSR-mediated intracellular calcium release, and thereby corresponded to the activation state of the CaSR. In presence of extracellular calcium, ambient alkalinization above pH 7.5 increased CaSR activity. Evaluation of the CaSR calcium sensitivity at various ambient proton concentrations revealed that this effect was due to a sensitization of the CaSR towards extracellular calcium. Conclusion: Coexpression with SK4 potassium channels provides a fast and sensitive approach to evaluate CaSR activity in Xenopus oocytes. As disclosed by this novel technique, CaSR activity is regulated by extracellular pH.
MeSH term(s)	Animals ; Base Sequence ; DNA, Complementary/genetics ; Female ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intermediate-Conductance Calcium-Activated Potassium Channels ; Ion Channel Gating ; Oocytes/metabolism ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated/genetics ; Potassium Channels, Calcium-Activated/metabolism ; Rats ; Receptors, Calcium-Sensing/genetics ; Receptors, Calcium-Sensing/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Xenopus laevis
Chemical Substances	DNA, Complementary ; Intermediate-Conductance Calcium-Activated Potassium Channels ; Kcnn4 protein, rat ; Potassium Channels, Calcium-Activated ; Receptors, Calcium-Sensing ; Recombinant Proteins ; extracellular calcium cation-sensing receptor, rat
Language	English
Publishing date	2005-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1111/j.1523-1755.2005.00069.x
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Zs.A 797: Show issues

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