Neonatal nephron loss during active nephrogenesis results in altered expression of renal developmental genes and markers of kidney injury

2021 ◽  
Author(s):  
Roman Raming ◽  
Nada Cordasic ◽  
Philipp Kirchner ◽  
Arif B Ekici ◽  
Fabian Fahlbusch ◽  
...  
Keyword(s):  
Tissue Repair ◽  
Animal Studies ◽  
Renal Damage ◽  
Kidney Injury ◽  
Preterm Neonates ◽  
Renal Development ◽  
Altered Expression ◽  
Renal Regeneration ◽  
Nephron Loss ◽  
Specific Regulation

Preterm neonates are at a high risk for nephron loss under adverse clinical conditions. Renal damage potentially collides with postnatal nephrogenesis. Recent animal studies suggest that nephron loss within this vulnerable phase leads to renal damage later in life. Nephrogenic pathways are commonly reactivated after kidney injury supporting renal regeneration. We hypothesized that nephron loss during nephrogenesis affects renal development which in turn impairs tissue repair after secondary injury. Neonates prior to 36 weeks of gestation show an active nephrogenesis. In rats, nephrogenesis is ongoing until day 10 after birth. Mimicking the situation of severe nephron loss during nephrogenesis, male pups were uninephrectomized at day 1 of life (UNXd1). A second group of males was uninephrectomized at postnatal day 14 (UNXd14), after terminated nephrogenesis. Age-matched controls were sham operated. Three days after uninephrectomy transcriptional changes in the right kidney were analyzed by RNA-sequencing, followed by functional pathway analysis. In UNXd1 1182 genes were differentially regulated, but only 143 genes showed a regulation both in UNXd1 and UNXd14. The functional groups "renal development" and "kidney injury" were among the most differentially regulated groups and revealed distinctive alterations. Reduced expression of candidate genes concerning renal development (Bmp7, Gdnf, Pdgf-B, Wt1) and injury (nephrin, podocin, Tgf-β1) were detected. The downregulation of Bmp7 and Gdnf persisted until day 28. In UNXd14 Six2 was upregulated and Pax2 downregulated. We conclude that nephron loss during nephrogenesis affects renal development and induces a specific regulation of genes which might hinder tissue repair after secondary kidney injury.

scholarly journals Evaluation of Fetal and Maternal Vancomycin-Induced Kidney Injury during Pregnancy in a Rat Model

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Medha D. Joshi ◽  
Gwendolyn M. Pais ◽  
Jack Chang ◽  
Khrystyna Hlukhenka ◽  
Sean N. Avedissian ◽  
...  
Keyword(s):  
Animal Studies ◽  
Renal Damage ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Tissue Homogenate ◽  
Tandem Mass ◽  
Pregnant Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Kidney Injury Molecule 1 ◽  
Rat Pup

ABSTRACT Previous literature suggests that maternal vancomycin crosses the placental barrier to the fetus. Further, early animal studies indicated that kidney injury was not observed in the progeny. These studies were conducted prior to the availability of sensitive biomarkers for kidney injury. Therefore, a previous finding of no renal damage to the infant may be misleading. Vancomycin was administered intravenously to pregnant rats at a dose of 250 mg/kg of body weight/day (N = 6 per trimester) on three consecutive gestational days (GD) during trimesters 1, 2, and 3 (T1, T2, and T3, respectively) in three independent cohorts. The dams carried to term and delivered vaginally on GD 21. Kidneys were harvested from dams and pups and homogenized. Samples were prepared by protein precipitation and injected in a liquid chromatography tandem mass spectrometer, and vancomycin was quantified. The kidney tissue homogenate from dams and pups were analyzed for kidney injury molecule-1 (KIM-1). As trimesters progressed, the quantity of vancomycin increased linearly in the kidneys of both rat dams and pups (P < 0.0001 for T1 and T3, P < 0.0001 for T2 and T3, and P < 0.0001 for T3 and T3 control for both rat dams and pups). KIM-1 concentrations in pup kidneys were significantly higher when dams were administered vancomycin in trimesters 1 (P = 0.0001) and 2 (P = 0.0024) than in controls in trimester 3. Data demonstrate persistence of vancomycin in maternal and rat pup kidneys in all three trimesters of pregnancy with associated damage to the kidney, as indicated by expression of KIM-1.

scholarly journals Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Norbert Kiss ◽  
Péter Hamar
Keyword(s):  
Acute Kidney Injury ◽  
Animal Studies ◽  
Renal Damage ◽  
Cell Injury ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Rodent Models ◽  
Histologic Appearance ◽  
Rats And Mice ◽  
To Receive

Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments.

scholarly journals Potential Renoprotective Effects of Silymarin Against Nephrotoxic Drugs: A Review of Literature

2012 ◽  
Vol 15 (1) ◽  
pp. 112 ◽  
Author(s):  
Foroud Shahbazi ◽  
Simin Dashti-Khavidaki ◽  
Hossein Khalili ◽  
Mahboob Lessan-Pezeshki
Keyword(s):  
Animal Studies ◽  
Renal Damage ◽  
Kidney Injury ◽  
Modern Medicine ◽  
Drug Induced ◽  
Substantial Impact ◽  
Hepatic Diseases ◽  
Nephrotoxic Drugs ◽  
Apoptotic Effects ◽  
Hospital Acquired

Drug-induced nephrotoxicity (DIN) accounts for up to sixty percent of hospital acquired acute kidney injury. Several efforts have been made to reduce drug-induced renal damage; however, DIN remains a matter of concern, with substantial impact on patients and the health system. Silymarin is a drug that has been used for many years in alternate and modern medicine for treating hepatic diseases. Its antioxidant, anti-inflammatory and anti-apoptotic effects make it an interesting herbal medicine, and these properties have implicated this compound as a potential renoprotective agent. Based on the findings from animal studies, this review concluded that silymarin might exert significant protective or ameliorative effects against drug-induced kidney disease, especially against cisplatin-induced renal damage. Whether the protective administration of silymarin could be an effective clinical pharmacological strategy to prevent DIN is a question that remains to be answered in clinical trials. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Regenerating tubular epithelial cells of the kidney

2020 ◽  
Author(s):  
Eleni Stamellou ◽  
Katja Leuchtle ◽  
Marcus J Moeller
Keyword(s):  
Animal Studies ◽  
Kidney Injury ◽  
Lineage Tracing ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Classical Concept ◽  
Tubular Cells ◽  
Renal Regeneration ◽  
Renal Tubular ◽  
Experimental Findings

Abstract Acute tubular injury accounts for the most common intrinsic cause for acute kidney injury. Normally, the tubular epithelium is mitotically quiescent. However, upon injury, it can show a brisk capacity to regenerate and repair. The scattered tubular cell (STC) phenotype was discovered as a uniform reaction of tubule cells triggered by injury. The STC phenotype is characterized by a unique protein expression profile, increased robustness during tubular damage and increased proliferation. Nevertheless, the exact origin and identity of these cells have been unveiled only in part. Here, we discuss the classical concept of renal regeneration. According to this model, surviving cells dedifferentiate and divide to replace neighbouring lost tubular cells. However, this view has been challenged by the concept of a pre-existing and fixed population of intratubular progenitor cells. This review presents a significant body of previous work and animal studies using lineage-tracing methods that have investigated the regeneration of tubular cells. We review the experimental findings and discuss whether they support the progenitor hypothesis or the classical concept of renal tubular regeneration. We come to the conclusion that any proximal tubular cell may differentiate into the regenerative STC phenotype upon injury thus contributing to regeneration, and these cells differentiate back into tubular cells once regeneration is finished.

Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications

2012 ◽  
Vol 303 (2) ◽  
pp. F180-F191 ◽  
Author(s):  
Wilfred Lieberthal ◽  
Jerrold S. Levine
Keyword(s):  
Animal Studies ◽  
Kidney Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Graft Function ◽  
Kidney Injury ◽  
Cyst Formation ◽  
Renal Diseases ◽  
Therapeutic Implications ◽  
The Metabolic Syndrome ◽  
Renal Regeneration

The mTOR pathway plays an important role in a number of common renal diseases, including acute kidney injury (AKI), diabetic nephropathy (DN), and polycystic kidney diseases (PKD). The activity of mTOR complex 1 (mTORC1) is necessary for renal regeneration and repair after AKI, and inhibition of mTORC1 by rapamycin has been shown to delay recovery from ischemic AKI in animal studies, and to prolong delayed graft function in humans who have received a kidney transplant. For this reason, administration of rapamycin should be delayed or discontinued in patients with AKI until full recovery of renal function has occurred. On the other hand, inappropriately high mTORC1 activity contributes to the progression of the metabolic syndrome, the development of type 2 diabetes, and the pathogenesis of DN. In addition, chronic hyperactivity of mTORC1, and possibly also mTORC2, contributes to cyst formation and enlargement in a number of forms of PKD. Inhibition of mTOR, using either rapamycin (which inhibits predominantly mTORC1) or “catalytic” inhibitors (which effectively inhibit both mTORC1 and mTORC2), provide exciting possibilities for novel forms of treatment of DN and PKD. In this second part of the review, we will examine the role of mTOR in the pathophysiology of DN and PKD, as well as the potential utility of currently available and newly developed inhibitors of mTOR to slow the progression of DN and/or PKD.

Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors

2019 ◽  
Vol 71 (5) ◽  
Author(s):  
Rita Ladeiras ◽  
Filipa Flor-De-Lima ◽  
Henrique Soares ◽  
Bárbara Oliveira ◽  
Hercília Guimarães
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Gestational Age ◽  
Kidney Injury ◽  
Preterm Neonates

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

scholarly journals Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Female Rats ◽  
Male Rats ◽  
Renal Diseases ◽  
Transgenic Rat ◽  
Increased Risk ◽  
Before And After

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.

Diuretic therapy and acute kidney injury in preterm neonates and infants

2021 ◽  
Author(s):  
Tahagod H. Mohamed ◽  
Brett Klamer ◽  
John D. Mahan ◽  
John D. Spencer ◽  
Jonathan L. Slaughter
Keyword(s):  
Acute Kidney Injury ◽  
Diuretic Therapy ◽  
Kidney Injury ◽  
Preterm Neonates ◽  
Neonates And Infants
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