AKI Repair

Sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin (Dapa), exhibited nephroprotective effects in patients with chronic kidney disease (CKD). We assessed the efficacy of short-term Dapa administration following acute kidney injury (AKI) in preventing CKD. Male Wistar rats were randomly assigned to Sham surgery, bilateral ischemia for 30 minutes (abbreviated as IR), and IR + Dapa groups. Daily treatment with Dapa was initiated just 24 hours after IR and maintained for only 10 days. Initially, rats were euthanized at this point to study early renal repair...

Acute Kidney injury (AKI) is characterized by a sudden, and usually reversible, decline in kidney function. In mice, ischemia reperfusion injury (IRI) is commonly used to model the pathophysiological features of clinical AKI. Macrophages are a unifying feature of IRI as they regulate both the initial injury response as well as the long-term outcome following resolution of injury. Initially, macrophages in the kidney take on a pro-inflammatory phenotype characterized by production of inflammatory cytokines such as CCL2 (MCP-1), IL-6, IL-1β, and TNF-α...

Acute kidney injury (AKI) frequently occurs in patients with chronic kidney disease (CKD) and in turn, may cause or accelerate CKD. Therapeutic options in AKI are limited and mostly relate to replacement of kidney function until the kidneys recover spontaneously. Furthermore, there is no treatment that prevents the AKI-to-CKD transition. Regulated necrosis has recently emerged as key player in kidney injury. Specifically, there is functional evidence for a role of necroptosis, ferroptosis or pyroptosis in AKI and the AKI-to-CKD progression...

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD...

Almost every cell in the kidney, including renal tubular epithelial cells, has a primary cilium, which is a membrane-bound, hair-like structure protruding from the cellular surface. Dysfunction of primary cilia has been linked to a wide spectrum of human genetic diseases, termed ciliopathies. Planar cell polarity (PCP) refers to the coordinated alignment of cells along the cell sheet or tissue plane, a fundamental process in embryo development and organogenesis. Interestingly, there is evidence that primary cilium and PCP are interconnected...

Glomerulonephritis are renal disorders resulting from different pathogenic mechanisms (i.e., autoimmunity, complement, inflammatory activation, etc.). Clarifying details of the pathogenic cascade is basic to limit the progression from starting inflammation to degenerative stages. The balance between tissue injury, activation of protective systems and renal tissue repair determines the final outcome. Induction of an oxidative stress is part of glomerular inflammation and activation of protective antioxidant systems has a crucial role in reducing tissue effects...

Background: Renal repair is closely related to the prognosis of acute kidney injury (AKI) and has attracted increasing attention in the research field. However, there is a lack of a comprehensive bibliometric analysis in this research area. This study aims at exploring the current status and hotspots of renal repair research in AKI from the perspective of bibliometrics. Methods: Studies published between 2002 and 2022 related to kidney repair after AKI were collected from Web of Science core collection (WoSCC) database...

BACKGROUND: AKI triggers a proliferative response as part of an intrinsic cellular repair program, which can lead to adaptive renal repair, restoring kidney structure and function, or maladaptive repair with the persistence of injured proximal tubule cells (PTCs) and an altered kidney structure. However, the cellular and molecular understanding of these repair programs is limited. METHODS: To examine chromatin and transcriptional responses in the same cell upon ischemia-reperfusion injury (IRI), we combined genetic fate mapping of cycling (Ki67+) cells labeled early after IRI with single-nucleus multiomics-profiling transcriptome and chromatin accessibility in the same nucleus-and generated a dataset of 83,315 nuclei...

A common drawback of metabolic analyses of complex biological samples is the inability to consider cell-to-cell heterogeneity in the context of an organ or tissue. To overcome this limitation, we present an advanced high-spatial-resolution metabolomics approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) combined with isotope tracing. This method allows mapping of cell-type-specific dynamic changes in central carbon metabolism in the context of a complex heterogeneous tissue architecture, such as the kidney...

The kidney has a remarkable ability of repair after acute kidney injury (AKI). However, when injury is severe or persistent, the repair is incomplete or maladaptive and may lead to chronic kidney disease (CKD). Maladaptive kidney repair involves multiple cell types and multifactorial processes, of which inflammation is a key component. In the process of inflammation, there is a bidirectional interplay between kidney parenchymal cells and the immune system. The extensive and complex crosstalk between renal tubular epithelial cells and interstitial cells, including immune cells, fibroblasts, and endothelial cells, governs the repair and recovery of the injured kidney...

Extracellular vesicles are released by the majority of cell types and circulate in body fluids. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence has established a central role of extracellular vesicles in kidney physiology and pathology. Urinary extracellular vesicles mediate crosstalk between glomerular and tubular cells and between different segments of the tubule, whereas circulating extracellular vesicles mediate organ crosstalk and are involved in the amplification of kidney damage and inflammation...

BACKGROUND: After kidney injury, macrophages transition from initial proinflammatory activation to a proreparative phenotype characterized by expression of arginase-1 ( Arg1 ), mannose receptor 1 ( Mrc1 ), and macrophage scavenger receptor 1 ( Msr1 ). The mechanism by which these alternatively activated macrophages promote repair is unknown. METHODS: We characterized the macrophage and renal responses after ischemia-reperfusion injury with contralateral nephrectomy in LysM-Cre;Arg1fl/fl mice and littermate controls and used in vitro coculture of macrophages and tubular cells to determine how macrophage-expressed arginase-1 promotes kidney repair...

The kidney has a remarkable regenerative capacity. In response to ischemic or toxic injury, proximal tubule cells can proliferate to rebuild damaged tubules and restore kidney function. However, severe acute kidney injury (AKI) or recurrent AKI events can lead to maladaptive repair and disease progression from AKI to chronic kidney disease (CKD). The application of single cell technologies has identified injured proximal tubule cell states weeks after AKI, distinguished by a pro-inflammatory senescent molecular signature...

The kidneys play an indispensable role in glucose homeostasis via glucose reabsorption, production, and utilization. Conversely, aberrant glucose metabolism is involved in the onset, progression, and prognosis of kidney diseases, including acute kidney injury (AKI). In this review, we describe the regulation of glucose homeostasis and related molecular factors in kidneys under normal physiological conditions. Furthermore, we summarize recent investigations about the relationship between glucose metabolism and different types of AKI...

Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all...

The ability of the kidney to regenerate successfully after injury is lost with advancing age, chronic kidney disease, and after irradiation. The factors responsible for this reduced regenerative capacity remain incompletely understood, with increasing interest in a potential role for cellular senescence in determining outcomes after injury. Here, we demonstrated correlations between senescent cell load and functional loss in human aging and chronic kidney diseases including radiation nephropathy. We dissected the causative role of senescence in the augmented fibrosis occurring after injury in aged and irradiated murine kidneys...

Acute kidney injury (AKI) is a major complication in critically ill patients and affects up to 50% of those admitted to intensive care units. Causes of AKI include patient specific factors (susceptibility: e.g. age, pre-existing chronic kidney disease, chronic heart failure, diabetes) and patient unspecific factors (exposure: e.g. sepsis, hypovolemia, cardiac surgery, nephrotoxin application). Mortality of severe AKI is in the range of 40 - 50%.AKI is accompanied by volume overload, electrolyte disorders, acidosis, and uremia...

Our aging population is growing and developing treatments for age-related diseases such as Alzheimer's and Parkinson's disease has taken on an increasing urgency and is accompanied by high public awareness. The already high and rising incidence of acute kidney injury (AKI) in the elderly, however, has received relatively little attention despite the potentially fatal outcomes associated with an episode of AKI in this age group. When discussing AKI and aging, one should consider two aspects: first, elderly patients have an increased susceptibility to an AKI episode, and second, they have decreased kidney repair after AKI given the high incidence of progression to chronic kidney disease (CKD)...

Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery and intrarenal hypoxia is a hallmark of AKI, and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in recovery from an ischemic insult is presently unclear. The present study was designed to investigate 1) the role of systemic hypoxia in the acute progression and recovery of AKI, and 2) if increased intrarenal oxygenation improves recovery from an ischemic insult...

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) have been recognized as a promising cell-free therapy for acute kidney injury (AKI), which avoids safety concerns associated with direct cell engraftment. However, low stability and retention of MSC-EVs have limited their therapeutic efficacy. RGD (Arg-Gly-Asp) peptide binds strongly to integrins, which have been identified on the surface of MSC-EV membranes; yet RGD has not been applied to EV scaffolds to enhance and prolong bioavailability...