Peritoneal and renal DKK3 clearance in peritoneal dialysis.

Background: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis.

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.

High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation.

Kidney medullary sodium chloride concentrations induce neutrophil and monocyte extracellular DNA traps that defend against pyelonephritis in vivo.

Urinary tract infections are common. Here, we delineate a role of extracellular DNA trap (ET) formation in kidney antibacterial defense and determine mechanisms of their formation in the hyperosmotic environment of the kidney medulla. ET of granulocytic and monocytic origin were present in the kidneys of patients with pyelonephritis along with systemically elevated citrullinated histone levels.

CD4 T cells produce GM-CSF and drive immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12.

GM-CSF in glomerulonephritisDespite glomerulonephritis being an immune-mediated disease, the contributions of individual immune cell types are not clear. To address this gap in knowledge, Paust . characterized pathological immune cells in samples from patients with glomerulonephritis and in samples from mice with the disease.

NT-proBNP as predictor of major cardiac events after renal transplantation in patients with preserved left ventricular ejection fraction.

Background: For the improvement of outcome after renal transplantation it is important to predict future risk of major adverse cardiac events as well as all-cause mortality. We aimed to determine the relationship of pre-transplant NT-proBNP with major adverse cardiac events and all-cause mortality after transplant in patients on the waiting-list with preserved left ventricular ejection fraction.

Patients And Methods: We included 176 patients with end-stage renal disease and preserved left ventricular ejection fraction who received a kidney transplant.

Pre-transplant serum Beta Trace Protein indicates risk for post-transplant major cardiac adverse events.

Background: Beta Trace Protein (BTP) is a biomarker for residual kidney function which has been linked to cardiovascular and all-cause mortality in haemodialysis patients. Following renal transplantation, recipients remain at increased risk for cardiovascular events compared with the general population. We aimed to determine the relationship of pre-transplant BTP to major adverse cardiac events (MACE) in patients following kidney transplantation.

Annexin A1 exerts renoprotective effects in experimental crescentic glomerulonephritis.

Non-resolving inflammation plays a critical role during the transition from renal injury towards end-stage renal disease. The glucocorticoid-inducible protein annexin A1 has been shown to function as key regulator in the resolution phase of inflammation, but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Acute crescentic glomerulonephritis was induced in annexin A1-deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents.

Generation of an alpaca serum that induces immune-mediated crescentic glomerulonephritis in mice.

Crescentic glomerulonephritis (cGN) is the most aggressive form of glomerulonephritis in humans. A widely studied mouse model is induced by sheep or rabbit antisera raised against murine renal cortical antigens. We here, report that Alpaca readily produce ample amounts of antisera that induces pathology in mice, resembling human disease regarding crescent formation, proteinuria, infiltrating immune cells and a significant Th1, but not Th17 immune response.

Single cell versus single nucleus: transcriptome differences in the murine kidney after ischemia-reperfusion injury.

The kidney is a complex organ, which consists of multiple components with highly diverse cell types. A detailed understanding of these cell types in health and disease is crucial for the future development of preventive and curative treatment strategies. In recent years, single-cell RNA sequencing (scRNAseq) and single-nucleus RNA sequencing (snRNAseq) technology has opened up completely new possibilities in investigating the variety of renal cell populations in physiological and pathological states.

Induction of ferroptosis selectively eliminates senescent tubular cells.

The accumulation of senescent cells is an important contributor to kidney aging, chronic renal disease, and poor outcome after kidney transplantation. Approaches to eliminate senescent cells with senolytic compounds have been proposed as novel strategies to improve marginal organs. While most existing senolytics induce senescent cell clearance by apoptosis, we observed that ferroptosis, an iron-catalyzed subtype of regulated necrosis, might serve as an alternative way to ablate senescent cells.

Myeloid CCR2 Promotes Atherosclerosis after AKI.

Background: The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms.

Renal medullary osmolytes NaCl and urea differentially modulate human tubular cell cytokine expression and monocyte recruitment.

Renal immune cells serve as sentinels against ascending bacteria but also promote detrimental inflammation. The kidney medulla is characterized by extreme electrolyte concentrations. We here address how its main osmolytes, NaCl and urea, regulate tubular cell cytokine expression and monocyte chemotaxis.

Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures.

Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged.

Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice.

Background: Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice.

Long-term B cell depletion associates with regeneration of kidney function.

Background: Chronic kidney disease (CKD) is a common condition that increases mortality and the risk of cardiovascular and other morbidities regardless of underlying renal condition. Chronic inflammation promotes renal fibrosis. Recently, renal B cell infiltrates were described in chronic kidney disease of various etiologies beyond autoimmunity.

A flow cytometry approach reveals heterogeneity in conventional subsets of murine renal mononuclear phagocytes.

Mononuclear phagocytes (MNPs) participate in inflammation and repair after kidney injury, reflecting their complex nature. Dissection into refined functional subunits has been challenging and would benefit understanding of renal pathologies. Flow cytometric approaches are limited to classifications of either different MNP subsets or functional state.

Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease.

Attraction, retention, and differentiation of leukocytes to and within the kidney are governed by chemokines. The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 are exemplary in this regard as they are highly expressed and further upregulated in a range of kidney diseases. CX3CL1 is chiefly produced by renal endothelium and tubular epithelium, where it promotes leukocyte attraction.

Advances in the pharmacological management of bacterial peritonitis.

Bacterial peritonitis is an infection with high mortality if not treated immediately. In the absence of an intraabdominal source of infection, bacterial peritonitis may arise in patients with liver cirrhosis, in patients on peritoneal dialysis (PD) for end-stage renal disease or in patients with tuberculosis. In patients with cirrhosis, bacterial peritonitis may trigger acute on chronic liver failure with substantial mortality despite optimal treatment.

SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate.

Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin.

Peritoneal dialysate-range hypertonic glucose promotes T-cell IL-17 production that induces mesothelial inflammation.

Peritoneal dialysis (PD) employs hypertonic glucose to remove excess water and uremic waste. Peritoneal membrane failure limits its long-term use. T-cell cytokines promote this decline.