Preterm Neonatal Urinary Renal Developmental and acute kidney injury Metabolomic Profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Urine
DISEASE(S): Kidney Disease
PROVIDER: ST000050 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Hypoxic ischemic encephalopathy (HIE) is associated with acute kidney injury (AKI) in neonates with birth asphyxia. This study aimed to utilize urinary biomarkers to characterize AKI in an established neonatal rat model of HIE. Day 7 Sprague-Dawley rat pups underwent HIE using the Rice-Vannucci model (unilateral carotid ligation followed by 120 mins of 8% oxygen). Controls included no surgery and sham surgery. Weights and urine for biomarkers (NGAL, osteopontin, KIM-1, albumin) were collected the day prior, daily for 3 days post-intervention, and at sacrifice day 14. Kidneys and brains were processed for histology. HIE pups displayed histological evidence of kidney injury including damage to the proximal tubules, consistent with resolving acute tubular necrosis, and had significantly elevated urinary levels of NGAL and albumin compared to sham or controls 1-day post-insult that elevated for 3 days. KIM-1 significantly increased for 2 days post-HIE. HIE did not significantly alter osteopontin levels. Seven days post-start of experiment, controls were 81.2% above starting weight compared to 52.1% in HIE pups. NGAL and albumin levels inversely correlated with body weight following HIE injury. The AKI produced by the Rice-Vannucci HIE model is detectable by urinary biomarkers, which can be used for future studies of treatments to reduce kidney injury.
| S-EPMC9768655 | biostudies-literature
Project description:Background There is little known about the contribution of microRNAs (miRNAs) in the recovery from acute kidney injury (AKI). This study aimed to discover and validate miRNA profiles for predicting renal recovery from severe AKI. Patients and methods A prospective observational study was conducted between June 2020 and January 2021. Urine and serum samples of participants with AKI stage 3 were collected from two groups: renal recovery and renal non-recovery. Transcriptomic analysis was performed using nCounter miRNA Expression Assay. Expression levels of candidate miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results The discovery phase identified 18 and 11 differentially expressed miRNAs that were statistically significant between the two groups in urine and serum specimens, respectively. Top candidate miRNAs selected included miR-556-3p, miR-1915-3p, miR-4284, miR-32-5p, miR-96-5p, and miR-556-5p in urine, and miR-499b-5p, miR-30a-3p, miR-92b-3p and miR-770-5p in serum. This study enrolled 110 participants in the validation phase. The qRT-PCR analysis indicated that urine miR-556-3p was significantly higher in the renal recovery group than in the renal non-recovery group. Urine miR-556-3p alone predicted renal recovery with an area under the curve (AUC) of 0.64 (95%CI 0.52–0.75, p = 0.03). Combining the clinical model with urine miR-556-3p predicted renal recovery with an AUC of 0.83 (95%CI 0.75–0.92, p < 0.01). Conclusion This data provides evidence that microtranscriptome profiles of severe AKI patients with renal recovery differed from the non-recovery group. Urine miR-556-3p had the potential to improve the prediction of renal recovery from severe AKI. Supplementary Information The online version contains supplementary material available at 10.1186/s40560-022-00637-0.
| S-EPMC9523985 | biostudies-literature
Project description:BackgroundRecent animal studies have shown that mitochondrial dysfunction initiates and accelerates renal injury in sepsis, but its role in sepsis remains unknown. Mitochondrial stress or dying cells can lead to fragmentation of the mitochondrial genome, which is considered a surrogate marker of mitochondrial dysfunction. Therefore, we evaluated the efficiency of urinary mitochondrial DNA (UmtDNA) as a marker of renal dysfunction during sepsis-induced acute kidney injury (AKI).MethodsWe isolated DNA from plasma and urine of patients. mtDNA levels were quantified by quantitative PCR. Sepsis patients were divided into no AKI, mild AKI, and severe AKI groups according to RIFLE criteria. Additionally, cecal ligation and puncture (CLP) was established in rats to evaluate the association between UmtDNA and mitochondrial function.ResultsA total of 52 (49.5%) developed AKI among enrolled sepsis patients. Increased systemic mtDNA did not correlate with systemic inflammation or acute renal dysfunction in sepsis patients, while AKI did not have an additional effect on circulating mtDNA levels. In contrast, UmtDNA was significantly enriched in severe AKI patients compared with that in the mild AKI or no AKI group, positively correlated with plasma creatinine, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1, and inversely with the estimated glomerular filtration rate. Additionally, UmtDNA increased in rats following CLP-induced sepsis. UmtDNA was predictive of AKI development and correlated with plasma creatinine and blood urea nitrogen in the rat sepsis model. Finally, the UmtDNA level was inversely correlated with the cortical mtDNA copy number and relative expression of mitochondrial gene in the kidney.ConclusionAn elevated UmtDNA level correlates with mitochondrial dysfunction and renal injury in sepsis patients, indicating renal mitochondrial injury induced by sepsis. Therefore, UmtDNA may be regarded as a valuable biomarker for the occurrence of AKI and the development of mitochondria-targeted therapies following sepsis-induced AKI.
| S-EPMC5846356 | biostudies-literature
Project description:BackgroundAcute kidney injury represents a major threat to the transplanted kidney. Nevertheless, these kidneys have the potential to fully recover. Tubular regeneration following acute kidney injury is driven by the regenerative potential of tubular cells originating from a tubular stem cell pool. We investigated urinary sediments of acute kidney injury transplanted patients and compared it to those of non-transplanted patients. Thereby we discovered tubular cell agglomerates, which have not been described in vivo. We hypothesized that these so-called nephrospheres were associated with recovery from acute kidney injury.MethodsUrine sediment of 45 kidney-transplanted and 19 non-transplanted individuals was investigated. Nephrospheres were isolated and stained for several molecular markers including aquaporin 1 (AQP1) and calcium sensing receptor (CASR). Nephrospheres were cultured to examine their growth behavior in vitro. In addition, quantitative PCR for CASR, AQP1, and podocin (NPHS2) was performed.ResultsNephrospheres were excreted in the urine of 17 kidney-transplant recipients 7 days after onset of acute kidney injury and were detectable over several days until kidney function was recovered to baseline creatinine levels. None were found in the urine of non-transplanted individuals. Nephrospheres were either AQP1+/CASR+ or AQP1-/CASR+ and could be cultured for 27 days. Mitotic cells could still be visualized after 17 days in culture. Quantitative PCR detected AQP1 in both kidney-transplanted and non-transplanted individuals during the phase of creatinine decline. As a limitation qPCR was only performed for the entire urinary sediment.ConclusionsNephrospheres are three dimensional tubular cell agglomerates which appeared in urine of kidney transplant recipients recovering from acute kidney injury. Appearance of nephrospheres in urine was independent of the duration after kidney transplantation. Nephrospheres proliferated in cell culture and kept expressing kidney specific marker. Presence of nephrospheres in urine showed a specificity of 100% and a sensitivity of 60.71% for recovery.
| S-EPMC6617660 | biostudies-literature
Project description:Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.
| S-EPMC5487594 | biostudies-literature
Project description:Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by quantitative PCR. Patients were stratified into no AKI, stable AKI, and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 h of reperfusion. UmtDNA increased in mice after 10-15 min of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus UmtDNA may serve as valuable biomarker for the development of mitochondrial-targeted therapies in AKI.
| S-EPMC4675682 | biostudies-literature
Project description:The kidney is comprised of heterogeneous cell populations that function together to perform a number of tightly controlled, complex and interdependent processes. Renal endothelial cells contribute to vascular tone, regulation of blood flow to local tissue beds, modulation of coagulation and inflammation, and vascular permeability. Both ischemia and sepsis have profound effects on the renal endothelium, resulting in microvascular dysregulation resulting in continued ischemia and further injury. In recent years, the concept of the vascular endothelium as an organ that is both the source of and target for inflammatory injury has become widely appreciated. Here we revisit the renal endothelium in the light of ever evolving molecular advances.
| S-EPMC4476528 | biostudies-other
Project description:Although the importance of mitochondrial dysfunction in acute kidney injury (AKI) has been documented, noninvasive early biomarkers of mitochondrial damage are needed. We examined urinary ATP synthase subunit β (ATPSβ) as a biomarker of renal mitochondrial dysfunction during AKI. Mice underwent sham surgery or varying degrees (5, 10, or 15 min ischemia) of ischemia/reperfusion (I/R)-induced AKI. Serum creatinine, BUN, and neutrophil gelatinase-associated lipocalin were elevated only in the 15 min I/R group at 24 h. Immunoblot analysis of urinary ATPSβ revealed two bands (full length ∼52 kDa and cleaved ∼25 kDa), both confirmed as ATPSβ by LC-MS/MS, that increased at 24 h in 10- and 15-min I/R groups. These changes were associated with mitochondrial dysfunction evidenced by reduced renal cortical expression of mitochondrial proteins, ATPSβ and COX1, proximal tubular oxygen consumption, and ATP. Furthermore, in the 15-min I/R group, urinary ATPSβ was elevated until 72 h before returning to baseline 144 h after reperfusion with recovery of renal function. Evaluation of urinary ATPSβ in a nonalcoholic steatohepatitis model of liver injury only revealed cleaved ATPSβ, suggesting specificity of full-length ATPSβ for renal injury. Immunoblot analyses of patient urine samples collected 36 h after cardiac surgery revealed increased urinary ATPSβ levels in patients with postcardiac surgery-induced AKI. LC-MS/MS urinalysis in human subjects with AKI confirmed increased ATPSβ. These translational studies provide evidence that ATPSβ may be a novel and sensitive urinary biomarker of renal mitochondrial dysfunction and could serve as valuable tool for the testing of potential therapies for AKI and chemical-induced nephrotoxicity.
| S-EPMC4408963 | biostudies-literature
Project description:BackgroundWe tested the hypotheses that: 1) early exposure to increasing episodes of clinically relevant intermittent hypoxia (IH) is detrimental to the developing kidneys; and 2) there is a critical number of daily IH episodes which will result in irreparable renal damage that may involve angiotensin (Ang) II and endothelin (ET)-1.MethodsAt birth (P0), neonatal rat pups were exposed to brief IH episodes from the first day of life (P0) to P7 or from P0-P14. Pups were either euthanized immediately or placed in room air (RA) until P21. RA littermates served as controls. Kidneys were harvested at P7, P14, and P21 for histopathology; angiotensin converting enzyme (ACE), ACE-2, ET-1, big ET-1, and malondialdehyde (MDA) levels; immunoreactivity of ACE, ACE-2, ET-1, ET-2, ET receptors (ETAR, ETBR), and hypoxia inducible factor (HIF)1α; and apoptosis (TUNEL stain).ResultsHistopathology showed increased renal damage with 8-12 IH episodes/day, and was associated with Ang II, ACE, HIF1α, and apoptosis. ACE-2 was not expressed at P7, and minimally increased at P14. However, a robust ACE-2 response was seen during recovery with maximum levels noted in the groups recovering from 8 IH episodes/day. ET-1, big ET-1, ETAR, ETBR, and MDA increased with increasing levels of neonatal IH.ConclusionsChronic neonatal IH causes severe damage to the developing kidney with associated elevations in vasoconstrictors, suggesting hypertension, particularly with 8 neonatal IH episodes. ACE-2 is not activated in early postnatal life, and this may contribute to IH-induced vasoconstriction. Therapeutic targeting of ACE and ET-1 may help decrease the risk for kidney injury in the developing neonate to prevent and/or treat neonatal acute kidney injury and/or chronic kidney disease.
| S-EPMC8418040 | biostudies-literature
Project description:Some patients have a decline in renal function after contrast medium injection, and this phenomenon is called contrast-induced acute kidney injury (CI-AKI); a small number of people even suffer severe renal failure. To date, the mechanism of CI-AKI remains unclear. We aimed to identify novel potential biomarkers in the urine of patients with CI-AKI through LC-MS/MS and bioinformatics analysis. We enrolled patients who underwent coronary angiography (contrast agent: iohexol). The CI-AKI group included 4 cases, and the non-CI-AKI group included 20 cases. We mixed the 4 CI-AKI samples and 20 non-CI-AKI samples. Then, a 0.6 ml urine sample was used for proteome analysis with LC-MS/MS approach. Metascape, ExPASy, and the Human Protein Atlas were utilized for bioinformatics analysis. We obtained 724 and 830 urine proteins from the CI-AKI and non-CI-AKI groups, respectively. The distribution of the pI values and molecular weights (MWs) of postoperative urine proteins showed no significant difference between the CI-AKI group and the non-CI-AKI group. A total of 99differentially expressed proteins (DEPs) were detected, among which 18 proteins were detected only in tubule cells, and 19 proteins were detected in both tubule cells and glomeruli. With GO analysis, the GEPs were mainly associated with immune response and inflammation. Although biomarkers cannot be asserted from this single pilot study, our results may help advance the understanding of the mechanisms of CI-AKI and identify potential novel biomarkers for further investigation.
| S-EPMC8528309 | biostudies-literature