scholarly journals Hypoxia and Dysregulated Angiogenesis in Kidney Disease

2015 ◽  
Vol 1 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Shinji Tanaka ◽  
Tetsuhiro Tanaka ◽  
Masaomi Nangaku
Keyword(s):  
Kidney Disease ◽  
Adoptive Transfer ◽  
Kidney Diseases ◽  
Hypoxia Inducible Factor ◽  
Kidney Injury ◽  
Angiogenic Factor ◽  
Vegf Expression ◽  
Peritubular Capillaries ◽  
End Stage ◽  
Endothelial Growth Factor

Background: Accumulating evidence has demonstrated that renal hypoxia has a crucial role in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and AKI-to-CKD transition, ultimately culminating in end-stage kidney disease. Renal hypoxia in progressive CKD is intricately linked to persisting capillary loss, which is mainly due to dysregulated angiogenesis. Summary: In CKD, hypoxia-inducible factor (HIF) accumulates in the ischemic tubulointerstitium but fails to sufficiently stimulate angiogenic responses, partly because of blunted activation of HIF, which is best exemplified in diabetic kidney disease. In addition, vascular endothelial growth factor (VEGF) expression is downregulated, possibly because injured tubules are not able to express sufficient VEGF and inflammatory circumstances inhibit VEGF expression. The upregulation of antiangiogenic factors and the incompetence of endothelial progenitor cells (EPCs) may also play some roles in the inadequacy of capillary restoration. Administration of VEGF or angiopoietin-1 maintains peritubular capillaries in several kidney diseases; however, administration of a single angiogenic factor may lead to the formation of abnormal vessels and induce inflammation, resulting in worsening of hypoxia and tubulointerstitial fibrosis. HIF stabilization, which aims to achieve the formation of mature and stable vessels by inducing coordinated angiogenesis, is a promising strategy. Given that the effect of systemic HIF activation is highly context-dependent, further studies are needed to elucidate the precise roles of HIF in various kidney diseases. The adoptive transfer of EPCs or mesenchymal stem cells (MSCs) is a fascinating alternative strategy to restore the peritubular capillaries. Key Messages: Suppressed HIF activation and VEGF expression may be responsible for the dysregulated angiogenesis in progressive CKD. Administration of a single angiogenic factor can cause abnormal vessel formation and inflammation, leading to a detrimental result. Although further studies are warranted, HIF stabilization and adoptive transfer of EPCs or MSCs appear to be promising strategies to restore normal capillaries.

scholarly journals PROTON PUMP INHIBITORS AND THE RISK OF CHRONIC KIDNEY DISEASES: A CRITICAL REVIEW

2020 ◽  
pp. 11-14
Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
End Stage Renal Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Stage Renal Disease ◽  
End Stage

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.

scholarly journals Troponins, Acute Coronary Syndrome and Renal Disease: From Acute Kidney Injury Through End-stage Kidney Disease

2019 ◽  
Vol 14 (3) ◽  
pp. 187-190
Author(s):  
Debasish Banerjee ◽  
Charlotte Perrett ◽  
Anita Banerjee
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Left Ventricular ◽  
End Stage Kidney Disease ◽  
Chronic Kidney Diseases ◽  
Coronary Syndrome ◽  
End Stage ◽  
Cardiac Troponins

The diagnosis of acute coronary syndromes (ACS) is heavily dependent on cardiac biomarker assays, particularly cardiac troponins. ACS, particularly non-ST segment elevation MI, are more common in patients with acute kidney injury, chronic kidney disease (CKD) and end-stage kidney disease (ESKD), are associated with worse outcomes than in patients without kidney disease and are often difficult to diagnose and treat. Hence, early accurate diagnosis of ACS in kidney disease patients is important using easily available tools, such as cardiac troponins. However, the diagnostic reliability of cardiac troponins has been suboptimal in patients with kidney disease due to possible decreased clearance of troponin with acute and chronic kidney impairment and low levels of troponin secretion due to concomitant cardiac muscle injury related to left ventricular hypertrophy, inflammation and fibrosis. This article reviews the metabolism and utility of cardiac biomarkers in patients with acute and chronic kidney diseases. Cardiac troponins are small peptides that accumulate in both acute and chronic kidney diseases due to impaired excretion. Hence, troponin concentrations rise and fall with acute kidney injury and its recovery, limiting their use in the diagnosis of ACS. Troponin concentrations are chronically elevated in CKD and ESKD, are associated with poor prognosis and decrease the sensitivity and specificity for diagnosis of ACS. Yet, the evidence indicates that the use of high-sensitivity troponins can confirm or exclude a diagnosis of ACS in the emergency room in a significant proportion of kidney disease patients; those patients in whom the results are equivocal may need longer in-hospital assessment.

Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure

2016 ◽  
Vol 41 (1-3) ◽  
pp. 144-150 ◽  
Author(s):  
Hon Liang Tan ◽  
John Q. Yap ◽  
Qi Qian
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Clinical Syndrome ◽  
Occurrence Rate ◽  
Cell Phenotype ◽  
Increased Risk ◽  
End Stage

Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.

scholarly journals Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

2021 ◽  
Vol 22 (21) ◽  
pp. 11857
Author(s):  
Peir-Haur Hung ◽  
Yung-Chien Hsu ◽  
Tsung-Hsien Chen ◽  
Chun-Liang Lin
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Epigenetic Modification ◽  
Kidney Injury ◽  
Diabetic Kidney ◽  
Kidney Fibrosis ◽  
Recent Advances ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease. The natural history of DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated glomerular filtration rate, and, ultimately, kidney failure. It is known that DKD is associated with metabolic changes caused by hyperglycemia, resulting in glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Hyperglycemia is also known to cause programmed epigenetic modification. However, the detailed mechanisms involved in the onset and progression of DKD remain elusive. In this review, we discuss recent advances regarding the pathogenic mechanisms involved in DKD.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

scholarly journals Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond

2021 ◽  
Vol 10 (6) ◽  
pp. 1175
Author(s):  
Emaad M. Abdel-Rahman ◽  
Faruk Turgut ◽  
Jitendra K. Gautam ◽  
Samir C. Gautam
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Severe Form ◽  
Clinical Syndrome ◽  
Current Evidence ◽  
Clinical Predictors ◽  
End Stage

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

scholarly journals Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Innate Immune ◽  
Cellular Mechanisms ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Capillary Rarefaction ◽  
Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Heme Oxygenase 1 ◽  
Wide Range ◽  
Significant Burden ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Effect

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

scholarly journals SARS-CoV-2 infection in hospitalized pediatric patients with kidney disease

2020 ◽  
Vol 10 (3) ◽  
Author(s):  
Flávia Silveira ◽  
Káthia Zuntini ◽  
Márcia Silveira ◽  
Lohanna Tavares ◽  
Juliana Mendes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Pediatric Patients ◽  
Kidney Diseases ◽  
Pediatric Population ◽  
Transplant Rejection ◽  
Kidney Injury ◽  
Underlying Disease ◽  
Great Divergence ◽  
Stage 1

OBJECTIVES: This study aims to present the confirmed cases of SARS-CoV-2 infection in pediatric patients with chronic and acute kidney diseases admitted to a tertiary pediatric hospital. METHODS: Descriptive and retrospective observational study with all children hospitalized between March and June 2020 who had, simultaneously, SARS-CoV-2 infection and renal pathologies. Of this total of patients, those who had another underlying disease besides the renal disease were excluded. RESULTS: During the period, nine children with kidney disease were admitted to the hospital and had infection confirmed by the new coronavirus through positive RT-PCR. Regarding the underlying disease, seven had only kidney disease, three of whom had stage 5 chronic kidney disease; one, with stage 1 chronic kidney disease; one, with cortic-sensitive nephrotic syndrome; and two, with acute kidney injury. Two patients in this study had already undergone kidney transplantation, used immunosuppressants and had their doses reduced due to the infectious condition. Only one required oxygen therapy and transfer to the intensive care unit, but was not intubated and returned to the ward within 24 hours. CONCLUSIONS: According to the cases described, the pediatric population with kidney disease, including those using immunosuppressants due to acute transplant rejection, seems to evolve without severe COVID-19, therefore there is no great divergence in relation to the population of the same healthy age group.

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