International Nephrology Masterclass in Chronic Kidney Disease: Rationale, Summary, and Future Perspectives.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers.

Empagliflozin in patients with autosomal dominant polycystic kidney disease (EMPA-PKD): study protocol for a randomised controlled trial.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that causes the formation of cysts primarily in the kidneys. The continuous growth of multiple cysts leads to the destruction of functional parenchyma, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD.

Left Ventricular Hypertrophy After Renal Transplantation: Systematic Review and Meta-analysis.

Background: Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH.

Grainyhead-like 2 Deficiency and Kidney Cyst Growth in a Mouse Model.

Key Points: Our study reveals segment-specific mechanisms in cystic kidney disease and suggests as a modifier of collecting duct–derived cyst progression. Our data demonstrate that genetic deletion of accelerates disease progression in a cystic mouse model.

Background: The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in maintaining the epithelial barrier properties of the kidney collecting duct and is important to osmoregulation.

Epithelial cell states associated with kidney and allograft injury.

The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes.

Discovery of a non-canonical GRHL1 binding site using deep convolutional and recurrent neural networks.

Background: Transcription factors regulate gene expression by binding to transcription factor binding sites (TFBSs). Most models for predicting TFBSs are based on position weight matrices (PWMs), which require a specific motif to be present in the DNA sequence and do not consider interdependencies of nucleotides. Novel approaches such as Transcription Factor Flexible Models or recurrent neural networks consequently provide higher accuracies.

Prevalence of pericardial effusion in autosomal dominant polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) has numerous extrarenal manifestations. Pericardial effusion (PE) may be an underrecognized complication with a reported prevalence of up to 35%. Our study is the first to systematically evaluate the prevalence of PE and associated risk factors in an ADPKD cohort outside the USA.

Protocol of the Berlin Long-term Observation of Vascular Events (BeLOVE): a prospective cohort study with deep phenotyping and long-term follow up of cardiovascular high-risk patients.

Introduction: The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.

Methods And Analysis: A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm.

Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia.

Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

Background: The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR).

Methods: A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up.

CSF-1 and Notch signaling cooperate in macrophage instruction and tissue repair during peripheral limb ischemia.

Ischemia causes an inflammatory response featuring monocyte-derived macrophages (MF) involved in angiogenesis and tissue repair. Angiogenesis and ischemic macrophage differentiation are regulated by Notch signaling Notch ligand Delta-like 1 (Dll1). Colony stimulating factor 1 (CSF-1) is an essential MF lineage factor, but its role in ischemic macrophage development and the interaction with Notch signaling is so far unclear.

The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression.

Introduction: Even during physiologic aging, the kidney experiences a loss of mass and a progressive functional decline. This is clinically relevant as it leads to an increased risk of acute and chronic kidney disease. The kidney tubular system plays an important role in the underlying aging process, but the involved cellular mechanisms remain largely elusive.

Strikingly conserved gene expression changes of polyamine regulating enzymes among various forms of acute and chronic kidney injury.

The polyamines spermidine and spermine and their common precursor molecule putrescine are involved in tissue injury and repair. Here, we test the hypothesis that impaired polyamine homeostasis contributes to various kidney pathologies in mice during experimental models of ischemia-reperfusion, transplantation, rhabdomyolysis, cyclosporine treatment, arterial hypertension, diabetes, unilateral ureteral obstruction, high oxalate feeding, and adenine-induced injuries. We found a remarkably similar pattern in most kidney pathologies with reduced expression of enzymes involved in polyamine synthesis together with increased expression of polyamine degrading enzymes.

Blood pressure dynamics during home blood pressure monitoring with a digital blood pressure coach-a prospective analysis of individual user data.

Introduction: Self-monitoring of blood pressure at home is a better predictor of prognosis and recommended in hypertension guidelines. However, the influence of baseline blood pressure category and measurement schedule on BP values during a period of home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application.

Methods: We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach.

Current practice of blood pressure measurement in Germany: a nationwide questionnaire-based survey in medical practices.

Purpose: Discrepancies exist between guideline recommendations and real-world practice of blood pressure (BP) measurements. The aim of this study was to assess, with a nationwide, questionnaire-based survey, the current practice of BP measurement and associated BP values in German medical practices.

Material And Methods: A nationwide survey in German medical practices was performed in the period from 10 May 2021 to 15 August 2021.

[What is confirmed in the treatment of chronic kidney disease?].

Chronic kidney disease (CKD) is defined as a relevant excretion of albumin into the urine or a reduction of the glomerular filtration rate (GFR) over a longer time period of ≥ 3 months. The causes of CKD are manifold, whereby the association with diabetes mellitus is the most frequent cause. Early stages of CKD affect approximately 10% of the total population.

The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage.

During embryonic development, the mesoderm undergoes patterning into diverse lineages including axial, paraxial, and lateral plate mesoderm (LPM). Within the LPM, the so-called intermediate mesoderm (IM) forms kidney and urogenital tract progenitor cells, while the remaining LPM forms cardiovascular, hematopoietic, mesothelial, and additional progenitor cells. The signals that regulate these early lineage decisions are incompletely understood.

Acute kidney injury biomarkers in the single-cell transcriptomic era.

Acute kidney injury (AKI) affects many hospitalized patients and is associated with increased morbidity and mortality even at milder and reversible stages. The current clinical definition relies on serum creatinine increases or decreased urinary output. However, both parameters are of limited use because of poor sensitivity, specificity, and timeliness.

Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.

Background: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.

Methods: We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria).

Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury.

Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting.

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.

Methods: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV).