Is there a dominant-negative effect in individuals with heterozygous disease-causing variants in COL4A3/COL4A4?

Alport syndrome (AS) shows a broad phenotypic spectrum ranging from isolated microscopic hematuria (MH) to end-stage kidney disease (ESKD). Monoallelic disease-causing variants in COL4A3/COL4A4 have been associated with autosomal dominant AS (ADAS) and biallelic variants with autosomal recessive AS (ARAS). The aim of this study was to analyze clinical and genetic data regarding a possible genotype-phenotype correlation in individuals with disease-causing variants in COL4A3/COL4A4.

MatricS-A novel tool for monitoring professional role development in surgical disciplines.

Introduction: Mentoring is an effective method for human resource development. Monitoring the process is important for individual mentee/mentor pairs as well as for program directors. Due to individual personality differences of both mentees and mentors and their respective interactions, it is challenging to monitor the individual development process of mentees in a structured manner.

High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer.

Background: The cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet.

Learning in peer teaching of patient relations and communication skills at the "Anamnesegruppen" Munich - proof-of-concept and lessons learned.

Due to the ban on classroom teaching during the pandemic, the Munich "Anamnesegruppen" had to be switched to e-learning at short notice. There were no established concepts for this, which is why digitalization was piloted and evaluated for feasibility. "Anamnesegruppen" have existed for over 50 years and are organized as independent student peer teaching.

Isn't here just there without a "t" - to what extent can digital Clinical Case Discussions compensate for the absence of face-to-face teaching?

COVID-19 challenges curriculum managers worldwide to create digital substitutes for classroom teaching. Case-based teaching formats under expert supervision can be used as a substitute for practical bedside teaching, where the focus is on teaching clinical reasoning skills. For medical students of LMU and TU Munich, the interactive, case-based, and supervised teaching format of Clinical Case Discussion (CCD) was digitised and implemented as dCCD in their respective curricula.

[Mentoring in urological postgraduate training : Use of a competence matrix for the evaluation of results].

Objectives: For the professional development of junior employees, sufficient competence is decisive for their career. The mentoring programme Urology Roadmap provides residents career planning in various roles (junior staff member, developer, networker, multiplier). To date, no data are available on the extent to which the role matrix instrument is suitable as a competence matrix for evaluating results.

Clinical Case Discussions - a novel, supervised peer-teaching format to promote clinical reasoning in medical students.

Clinical reasoning (CR) is a clinical core competence for medical students to acquire. While the necessity for CR teaching has been recognized since the early 20 century, to this day no consensus on how to best educate students in CR exists. Hence, few universities have incorporated dedicated CR teaching formats into their medical curriculum.

Identification of disease-causing variants by comprehensive genetic testing with exome sequencing in adults with suspicion of hereditary FSGS.

In about 30% of infantile, juvenile, or adolescent patients with steroid-resistant nephrotic syndrome (SRNS), a monogenic cause can be identified. The histological finding in SRNS is often focal segmental glomerulosclerosis (FSGS). Genetic data on adult patients are scarce with low diagnostic yields.

[Impact of the experience of urological senior physicians in Germany on professional and personal aspects].

Background: Urological senior physicians in Germany are a heterogeneous group with various clinical priorities and career objectives. To date, there are no reliable data concerning the impact of the time span for which senior physicians have been holding their position on professional, personal and position-linked aspects.

Material And Methods: The objective of this study was a comparative analysis of perspectives, private and professional settings, specific job-related activities and individual professional goals of urological senior physicians in Germany based on their experience in this position assessed as number of years (dichotomised at 8 years as senior physician).

Exome Sequencing and Identification of Phenocopies in Patients With Clinically Presumed Hereditary Nephropathies.

Rationale & Objective: Hereditary nephropathies are clinically and genetically heterogeneous disorders. For some patients, the clinical phenotype corresponds to a specific hereditary disease but genetic testing reveals that the expected genotype is not present (phenocopy). The aim of this study was to evaluate the spectrum and frequency of phenocopies identified by using exome sequencing in a cohort of patients who were clinically suspected to have hereditary kidney disorders.

Can clinical case discussions foster clinical reasoning skills in undergraduate medical education? A randomised controlled trial.

Objective: Fostering clinical reasoning is a mainstay of medical education. Based on the clinicopathological conferences, we propose a case-based peer teaching approach called clinical case discussions (CCDs) to promote the respective skills in medical students. This study compares the effectiveness of different CCD formats with varying degrees of social interaction in fostering clinical reasoning.

[Prevention of "contrast-induced" acute kidney injury - practical considerations].

Acute kidney injury (AKI) episodes after iodine radiocontrast application are decreasing since non-ionic agents are routinely used. Retrospective studies (in total comprising more than 100 000 patients) DO NOT show increased AKI rates after CT scans with the application of radiocontrast (vs. uncontrasted CT scans).

Cognitive bias in professional hand hygiene and feedback: A national online-survey on overconfidence in Germany.

To evaluate learning motivation barriers in infection control and feedback competences, we conducted a national online survey in Germany. Among 767 healthcare workers, overconfidence effects could be detected independent from age, gender, profession, education, and hospital-size. The identified effects may impair learning motivation relevant for supervisors and educators in infection control.

Refractory lupus nephritis: a survey.

'Refractory lupus nephritis' is a frequently used term but poorly defined. We conducted a survey among nephrologists and rheumatologists to spot the diversity of perceptions of this term and to better understand the clinical practice related to 'refractory lupus nephritis'. A total of 145 questionnaires completed by lupus nephritis experts were available for analysis, of which 52% were nephrologists, 34% rheumatologists, and 13% internists.

IL-22 sustains epithelial integrity in progressive kidney remodeling and fibrosis.

IL-22, a member of the IL-10 cytokine family, accelerates tubule regeneration upon acute kidney injury, hence we speculated on a protective role also in chronic kidney disease. We quantified intrarenal IL-22 expression after unilateral ureteral (UUO) in wild-type mice and performed UUO in IL-22 knock-out animals. Obstruction phenotypic differences between IL22 and IL22 mice were assessed by histology, immunohistochemistry, immunofluorescence as well as western blotting and reverse-transcriptase quantitative PCR ex vivo.

Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in response to tissue injury.

Notch and interleukin-22 (IL-22) signaling are known to regulate tissue homeostasis and respond to injury in humans and mice, and the induction of endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two pathways in a hierarchical fashion. However in adults, the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-α ADAM metalloprotease converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs.

Tumor necrosis factor superfamily ligand mRNA expression profiles differ between humans and mice during homeostasis and between various murine kidney injuries.

Background: Several tumour necrosis factor (TNF) based therapeutics have already been approved for human use and several others are emerging. Therefore, we determined the mRNA expression levels of the TNF superfamily ligands (TNFSF) - e.g.

The innate immune system in human systemic lupus erythematosus.

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized.

Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis.

The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice.

Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease.

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls.

Next generation sequencing and functional analysis of patient urine renal progenitor-derived podocytes to unravel the diagnosis underlying refractory lupus nephritis.

Often the cause of refractory lupus nephritis (RLN) remains unclear. We performed next-generation sequencing for podocyte genes in an RLN patient and identified compound heterozygosity for APOL1 risk alleles G1 and G2 and a novel homozygous c.[1049C>T]+[1049C>T] NPHS1 gene variant of unknown significance.

PMA and crystal-induced neutrophil extracellular trap formation involves RIPK1-RIPK3-MLKL signaling.

Neutrophil extracellular trap (NET) formation contributes to gout, autoimmune vasculitis, thrombosis, and atherosclerosis. The outside-in signaling pathway triggering NET formation is unknown. Here, we show that the receptor-interacting protein kinase (RIPK)-1-stabilizers necrostatin-1 or necrostatin-1s and the mixed lineage kinase domain-like (MLKL)-inhibitor necrosulfonamide prevent monosodium urate (MSU) crystal- or PMA-induced NET formation in human and mouse neutrophils.

Unmet medical needs in lupus nephritis: solutions through evidence-based, personalized medicine.

Lupus nephritis (LN) remains a kidney disease with significant unmet medical needs despite extensive clinical and translational research over the past decade. These include the need to (i) predict the individual risk for LN in a patient with systemic lupus erythematosus, (ii) identify the best therapeutic option for an individual patient, (iii) distinguish chronic kidney damage from active immunologic kidney injury, (iv) develop efficient treatments with acceptable or no side effects and improve the design of randomized clinical trials so that effective drugs demonstrate efficacy. This review discusses the underlying reasons for these unmet medical needs and options of how to overcome them in the future.

Interleukin-22 in kidney injury and regeneration.

Interleukins have become well-known regulators of innate and adaptive immunity-related tissue inflammation. Recently, IL-22 has gained a lot of interest for its unique functions in maintaining and regaining epithelial integrity. IL-22 is exclusively secreted by different immune cell subsets, while IL-22 receptors are mainly expressed by epithelial cells.