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 Pathogenic and protective role of macrophages in kidney disease

2013 ◽  
Vol 305 (1) ◽  
pp. F3-F11 ◽  
Author(s):  
Qi Cao ◽  
Yiping Wang ◽  
David C. H. Harris
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Protective Role ◽  
Therapeutic Use ◽  
Disease Type ◽  
Dual Role ◽  
Murine Models

Macrophages (MΦ) are located throughout kidney tissue, where they play important roles in homeostasis, surveillance, tolerance, and cytoprotection. MΦ are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. Recent studies have identified a dual role for MΦ in several murine models of kidney disease. In this review, we discuss the pathogenic and protective roles of the various MΦ subsets in experimental and human kidney diseases and summarize current progress toward the therapeutic use of MΦ in kidney diseases.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Anna Julie Peired ◽  
Alessandro Sisti ◽  
Paola Romagnani
Keyword(s):  
Clinical Trials ◽  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Human Kidney ◽  
Consensus Protocol ◽  
Paracrine Factors ◽  
Cell Based Therapy

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose.

scholarly journals Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease

2018 ◽  
Vol 29 (10) ◽  
pp. 2529-2545 ◽  
Author(s):  
Yiqing Guo ◽  
Jesse Pace ◽  
Zhengzhe Li ◽  
Avi Ma’ayan ◽  
Zichen Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Kidney Disease ◽  
Actin Cytoskeleton ◽  
Rna Sequencing ◽  
Wilms Tumor ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Differentiation Markers ◽  
Podocyte Injury

BackgroundPodocyte injury is the hallmark of proteinuric kidney diseases, such as FSGS and minimal change disease, and destabilization of the podocyte’s actin cytoskeleton contributes to podocyte dysfunction in many of these conditions. Although agents, such as glucocorticoids and cyclosporin, stabilize the actin cytoskeleton, systemic toxicity hinders chronic use. We previously showed that loss of the kidney-enriched zinc finger transcription factor Krüppel-like factor 15 (KLF15) increases susceptibility to proteinuric kidney disease and attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte.MethodsWe induced podocyte-specific KLF15 in two proteinuric murine models, HIV-1 transgenic (Tg26) mice and adriamycin (ADR)-induced nephropathy, and used RNA sequencing of isolated glomeruli and subsequent enrichment analysis to investigate pathways mediated by podocyte-specific KLF15 in Tg26 mice. We also explored in cultured human podocytes the potential mediating role of Wilms Tumor 1 (WT1), a transcription factor critical for podocyte differentiation.ResultsIn Tg26 mice, inducing podocyte-specific KLF15 attenuated podocyte injury, glomerulosclerosis, tubulointerstitial fibrosis, and inflammation, while improving renal function and overall survival; it also attenuated podocyte injury in ADR-treated mice. Enrichment analysis of RNA sequencing from the Tg26 mouse model shows that KLF15 induction activates pathways involved in stabilization of actin cytoskeleton, focal adhesion, and podocyte differentiation. Transcription factor enrichment analysis, with further experimental validation, suggests that KLF15 activity is in part mediated by WT1.ConclusionsInducing podocyte-specific KLF15 attenuates kidney injury by directly and indirectly upregulating genes critical for podocyte differentiation, suggesting that KLF15 induction might be a potential strategy for treating proteinuric kidney disease.

scholarly journals Senescence marker activin A is increased in human diabetic kidney disease: association with kidney function and potential implications for therapy

2019 ◽  
Vol 7 (1) ◽  
pp. e000720 ◽  
Author(s):  
Xiaohui Bian ◽  
Tomás P Griffin ◽  
Xiangyang Zhu ◽  
Md Nahidul Islam ◽  
Sabena M Conley ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Human Kidney ◽  
Activin A ◽  
Diabetic Kidney ◽  
Mesenchymal Transition

ObjectiveActivin A, an inflammatory mediator implicated in cellular senescence-induced adipose tissue dysfunction and profibrotic kidney injury, may become a new target for the treatment of diabetic kidney disease (DKD) and chronic kidney diseases. We tested the hypothesis that human DKD-related injury leads to upregulation of activin A in blood and urine and in a human kidney cell model. We further hypothesized that circulating activin A parallels kidney injury markers in DKD.Research design and methodsIn two adult diabetes cohorts and controls (Minnesota, USA; Galway, Ireland), the relationships between plasma (or urine) activin A, estimated glomerular filtration rate (eGFR) and DKD injury biomarkers were tested with logistic regression and correlation coefficients. Activin A, inflammatory, epithelial-mesenchymal-transition (EMT) and senescence markers were assayed in human kidney (HK-2) cells incubated in high glucose plus transforming growth factor-β1 or albumin.ResultsPlasma activin A levels were elevated in diabetes (n=206) compared with controls (n=76; 418.1 vs 259.3 pg/mL; p<0.001) and correlated inversely with eGFR (rs=−0.61; p<0.001; diabetes). After eGFR adjustment, only albuminuria (OR 1.56, 95% CI 1.16 to 2.09) and tumor necrosis factor receptor-1 (OR 6.40, 95% CI 1.08 to 38.00) associated with the highest activin tertile. Albuminuria also related to urinary activin (rs=0.65; p<0.001). Following in vitro HK-2 injury, activin, inflammatory, EMT genes and supernatant activin levels were increased.ConclusionsCirculating activin A is increased in human DKD and correlates with reduced kidney function and kidney injury markers. DKD-injured human renal tubule cells develop a profibrotic and inflammatory phenotype with activin A upregulation. These findings underscore the role of inflammation and provide a basis for further exploration of activin A as a diagnostic marker and therapeutic target in DKD.

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 Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm

2019 ◽  
Author(s):  
Milena Miszczuk ◽  
Verena Müller ◽  
Christian E. Althoff ◽  
Andrea Stroux ◽  
Daniela Widhalm ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Strong Association ◽  
Renal Cysts ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Abdominal Aortic ◽  
And Control ◽  
Charité Berlin

AbstractAbdominal aortic aneurysms (AAA) primarily affect elderly men who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. Two groups of patients (100/group), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. SRC (73% vs. 57%; p<0.001) and CKD (31% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

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.

scholarly journals Role of calcitriol in modulating of placental dysfunction in pregnant women with chronic kidney disease

2020 ◽  
Vol 17 (4) ◽  
pp. 493-499
Author(s):  
G. S. Manasova ◽  
N. V. Didenkul ◽  
L. V. Mnich ◽  
Z. V. Chumak ◽  
N. V. Kuzmin
Keyword(s):  
Vitamin D ◽  
Kidney Disease ◽  
Pregnant Women ◽  
Kidney Diseases ◽  
Active Form ◽  
Decisive Role ◽  
Control Group ◽  
National Academy Of Sciences ◽  
Placental Dysfunction ◽  
Group I

The pleiotropic effects of vitamin D (VD), whose active form is synthesized in the kidneys, play a certain role both in forming and functioning the feto-placental system, including various pregnancy complications. The aim of the study was to evaluate the vitamin D status in pregnant women with placental dysfunction (PD) and chronic inflammatory kidney disease (CIKD). During 24–34 pregnancy weeks, 56 pregnant women with PD were examined (main group ‒ I); 24 patients (42.85 %) had chronic pyelonephritis (group IA). The control group (group II) had 31 conditionally healthy pregnant women. The total VD level in the blood was determined by ELISA; in addition to the general clinical standard examination, the urine also underwent bacteriological examination. The VD mean level in pregnant women with PD and CIKD was significantly lower than that in the control group (31.08 ± 7.2 and 45.42 ± 9.67 ng/ml (p <0.01)). Only 33.33 % of pregnant women in group IA had a VD optimum, as well as 93.55 % (p < 0.01) in the control group and 17.86 % in group I. 8.33 % of pregnant women had a VD deficiency in group IA (RR = 2.09; CI 95 % ‒ 1.8‒2.42). The patients with a VD-deficiency were absent in the control group. 58.33 % of women in group ІА had a suboptimal VD level and 6.45% in the control group (RR = 3.57; CI 95 % ‒ 1.62‒7.88). Bacteriuria was observed in all pregnant women with a VD-deficient or suboptimal level. At the optimum VD level, bacteriuria was diagnosed twice less (χ2 = 66.67; p <0.01). In patients with an inadequate VD level, CIKD was diagnosed 3.8 times more (RR = 3.57; CI 95 % ‒ 1.62‒7.88). 494 Proceedings of the National Academy of Sciences of Belarus. Medical series, 2020, vol. 17, no. 4, pp. 493–499 A significantly calcitriol reduction in pregnant women with placental dysfunction suggests that the deficiency or the suboptimal level of vitamin D and inflammatory kidney diseases may be the interdependent processes that play a decisive role in the formation of placental dysfunction.

scholarly journals Stem cell-based treatment of kidney diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 902-910
Author(s):  
Binbin Pan ◽  
Guoping Fan
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Acute Kidney Injury ◽  
Stem Cell ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Great Promise ◽  
Kidney Organoids

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.

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.

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