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Lin H, Ren Y, Cui J, Guo J, Wang M, Wang L, Su X, Qiao X. Nomogram risk prediction model for acute respiratory distress syndrome following acute kidney injury. Front Med (Lausanne) 2025; 12:1563425. [PMID: 40270504 PMCID: PMC12014638 DOI: 10.3389/fmed.2025.1563425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 03/28/2025] [Indexed: 04/25/2025] Open
Abstract
Background Acute respiratory distress syndrome (ARDS), a severe form of respiratory failure, can be precipitated by acute kidney injury (AKI), leading to a significant increase in mortality among affected patients. This study aimed to identify the risk factors for ARDS and construct a predictive nomogram. Methods We conducted a retrospective analysis of 1,241 AKI patients admitted to the Second Hospital of Shanxi Medical University from August 25, 2016, to December 31, 2023. The patients were divided into a study cohort (1,012 cases, including 108 with ARDS) and a validation cohort (229 cases, including 23 with ARDS). Logistic regression analysis was employed to identify the risk factors for ARDS, which were subsequently incorporated into the development of a nomogram. The predictive performance of the nomogram was assessed by AUC, calibration plots, and decision curve analyses, with external validation also performed. Results Six risk factors were identified and included in the nomogram: older age (OR = 1.020; 95%CI = 1.005-1.036), smoking history (OR = 1.416; 95%CI = 1.213-1.811), history of diabetes mellitus (OR = 1.449; 95%CI = 1.202-1.797), mean arterial pressure (MAP; OR = 1.165; 95%CI = 1.132-1.199), higher serum uric acid levels (OR = 1.002; 95%CI = 1.001-1.004), and higher AKI stage [(stage 1: reference), (stage 2: OR = 11.863; 95%CI = 4.850-29.014), (stage 3: OR = 41.398; 95%CI = 30.840-52.731)]. The AUC values were 0.951 in the study cohort and 0.959 in the validation cohort. Calibration and decision curve analyses confirmed the accuracy and clinical utility of the nomogram. Conclusion The nomogram, which integrates age, smoking history, diabetes mellitus history, MAP, and AKI stage, predicts the risk of ARDS in patients with AKI. This tool may aid in early detection and facilitate clinical decision-making.
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Affiliation(s)
- Hui Lin
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Yilin Ren
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Jing Cui
- Department of Endocrinology, Air Force Medical Center, Beijing, China
| | - Junnan Guo
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Mengzhu Wang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Lihua Wang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Xiaole Su
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
| | - Xi Qiao
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Kidney Disease Institute, Taiyuan, China
- Kidney Research Center of Shanxi Medical University, Taiyuan, China
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Zou YX, Kantapan J, Wang HL, Li JC, Su HW, Dai J, Dechsupa N, Wang L. Iron-Quercetin complex enhances mesenchymal stem cell-mediated HGF secretion and c-Met activation to ameliorate acute kidney injury through the prevention of tubular cell apoptosis. Regen Ther 2025; 28:169-182. [PMID: 39802634 PMCID: PMC11720445 DOI: 10.1016/j.reth.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/20/2024] [Accepted: 12/04/2024] [Indexed: 01/16/2025] Open
Abstract
Background Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms. Methods A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSCIronQ). Renal function, histology, and tubular cell apoptosis were analyzed three days post-treatment. In vitro, apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSCIronQ conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA sequencing (RNA-seq) was performed on MSCIronQ to explore the underlying mechanisms. Results Compared to MSC-treated AKI mice, those treated with MSCIronQ showed significantly improved renal function and histological outcomes, with reduced tubular cell apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSCIronQ-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSCIronQ on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models. Conclusions IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.
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Affiliation(s)
- Yuan-Xia Zou
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand
- Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Children's Diagnosis and Treatment Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jiraporn Kantapan
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Hong-Lian Wang
- Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jian-Chun Li
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand
- Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Hong-Wei Su
- Department of Urology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
| | - Jian Dai
- Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Neurology, The Third People's Hospital, Luzhou, 646000, China
| | - Nathupakorn Dechsupa
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Li Wang
- Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China
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Lin H, Guo X, Wang M, Su X, Qiao X. Risk factors and early prediction of cardiorenal syndrome type 3 among acute kidney injury patients: a cohort study. Ren Fail 2024; 46:2349113. [PMID: 38721900 PMCID: PMC11086006 DOI: 10.1080/0886022x.2024.2349113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 04/17/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram. METHODS In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort. RESULTS The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009-1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193-6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012-1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96--0.987; p < 0.001), homocysteine (OR = 1.05; 95%CI = 1.03-1.069; p < 0.001), AKI stage [(stage 1: reference), (stage 2: OR = 5.427; 95%CI = 1.781-16.534; p = 0.003), (stage 3: OR = 5.554; 95%CI = 2.234-13.805; p < 0.001)]. The nomogram exhibited excellent predictive performance with an AUC of 0.907 in the study cohort and 0.892 in the validation cohort. Calibration and decision curve analyses upheld its accuracy and clinical utility. CONCLUSIONS We developed a nomogram predicting CRS type 3 in AKI patients, incorporating 6 risk factors: age, CVD history, MAP, hemoglobin, homocysteine, and AKI stage, enhancing early risk identification and patient management.
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Affiliation(s)
- Hui Lin
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China
| | - Xiaoyu Guo
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mengzhu Wang
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China
| | - Xiaole Su
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China
| | - Xi Qiao
- Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China
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Lin KM, Su CC, Chen JY, Pan SY, Chuang MH, Lin CJ, Wu CJ, Pan HC, Wu VC. Biomarkers in pursuit of precision medicine for acute kidney injury: hard to get rid of customs. Kidney Res Clin Pract 2024; 43:393-405. [PMID: 38934040 PMCID: PMC11237332 DOI: 10.23876/j.krcp.23.284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 01/08/2024] [Accepted: 02/13/2024] [Indexed: 06/28/2024] Open
Abstract
Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI's pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.
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Grants
- MOST 107-2314-B-002-026-MY3, 108-2314B-002-058, 110-2314-B-002-241, 110-2314-B-002-239 Ministry of Science and Technology (MOST) of the Republic of China (Taiwan)
- NSTC 109-2314-B-002-174-MY3, 110-2314-B-002124-MY3, 111-2314-B-002-046, 111-2314-B-002-058 National Science and Technology Council
- PH-102-SP-09 National Health Research Institutes
- 109-S4634, PC-1246, PC-1309, VN109-09, UN109-041, UN110-030, 111-FTN0011 National Taiwan University Hospital
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Affiliation(s)
- Kun-Mo Lin
- Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Ching-Chun Su
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Szu-Yu Pan
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
| | - Min-Hsiang Chuang
- Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Cheng-Jui Lin
- Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Wu
- Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Heng-Chih Pan
- Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Primary Aldosteronism Center of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- NSARF (National Taiwan University Hospital Study Group of ARF), Taipei, Taiwan
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Beyegue E, Afna F, Walantini J, Tata CM, Abdoulaye MG, Njamen D, Zingue S, Ndinteh DT. Dietary supplementation with seeds of Sesamum indicum L. (pedaliaceae) mitigates the 7,12-dimethylbenz(a)anthracene-induced breast tumor burden in rats. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2024; 21:205-214. [PMID: 38515384 DOI: 10.1515/jcim-2023-0266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 03/03/2024] [Indexed: 03/23/2024]
Abstract
OBJECTIVES Sesamum indicum L. seeds; rich in zinc and lignans are endowed with antioxidant and immunomodulatory properties which attract research on their anticancer potential. Although many studies have reported the in vitro antitumor potential of S. indicum and its phytoconstituents, much is yet to be known about its in vivo effects. To fill this gap, the effects of dietary supplementation with seeds of S. indicum in 7,12-dimethylbenz(a)anthracene-exposed rats was assessed. METHODS 42 rats aged 30-35 days were randomized into six groups (n=6) as follows: the normal (NOR) and negative (DMBA) control groups were fed with standard diet; the positive control group (DMBA + Zinc) was fed with standard diet supplemented with commercial zinc (0.01 %); the test groups were fed with standard diet supplemented with S. indicum seeds in different proportions (6.25 , 12.5 and 25 %). Breast cancer was induced by a single administration of DMBA (50 mg/kg BW, s.c.) diluted in corn oil. The experiment lasted 20 weeks and afterward, tumor incidence; tumor burden, tumor volume, tumor micro-architecture and some biochemical parameters were evaluated. RESULTS As salient result, 100 % of rats in the DMBA group developed tumors, while rats feed with rat chow supplemented with S. indicum seeds (25 %) had a reduced incidence of tumors (33.3 %) and tumor volume (2.71 cm3 in sesame 25 % vs. 4.69 cm3 in the DMBA group, p˂0.01). The seeds (25 %) also slowed DMBA-induced neoplasm expansion in mammary ducts as compared to rats of DMBA group. CONCLUSIONS In summary, supplementation with S. indicum seeds slowed breast tumorigenesis via its antioxidant capacity.
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Affiliation(s)
- Eric Beyegue
- Department of Biochemistry, Faculty of Science, University of Yaounde 1, Yaounde, Cameroon
| | - Florence Afna
- Department of Life and Earth Sciences, Higher Teachers' Training College, 310136 University of Maroua , Maroua, Cameroon
| | - Jonas Walantini
- Department of Life and Earth Sciences, Higher Teachers' Training College, 310136 University of Maroua , Maroua, Cameroon
| | - Charlotte Mungho Tata
- Department of Chemical Sciences, Faculty of Science, 61799 University of Johannesburg , Doornfontein, South Africa
- Department of Biochemistry, Faculty of Science, University of Bamenda, P.O. Box 396 Bambili, Cameroon
| | - Malla Gambo Abdoulaye
- Department of Life and Earth Sciences, Higher Teachers' Training College, 310136 University of Maroua , Maroua, Cameroon
| | - Dieudonné Njamen
- Department of Chemical Sciences, Faculty of Science, 61799 University of Johannesburg , Doornfontein, South Africa
- Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon
| | - Stéphane Zingue
- Department of Chemical Sciences, Faculty of Science, 61799 University of Johannesburg , Doornfontein, South Africa
- Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon
| | - Derek Tantoh Ndinteh
- Department of Chemical Sciences, Faculty of Science, 61799 University of Johannesburg , Doornfontein, South Africa
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Demirci B, Akın B, Gündoğan S, Özbilir Gİ, Alkan MO, Coşkun A. Hydronephrosis and pelvic rupture due to calculus with completely normal laboratory results. EMERGENCY CARE JOURNAL 2024. [DOI: 10.4081/ecj.2024.12230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024] Open
Abstract
Both side pain and urinary system pathologies are common reasons for admission to emergency departments. Spontaneous renal pelvic rupture is also very rare. Existing renal anomalies and calculi also increase the risk of rupture. Here, we present a 50-year-old male case who developed unilateral renal pelvis rupture spontaneously without trauma.
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Gao P, Cao Y, Ma L. Regulation of soluble epoxide hydrolase in renal-associated diseases: insights from potential mechanisms to clinical researches. Front Endocrinol (Lausanne) 2024; 15:1304547. [PMID: 38425758 PMCID: PMC10902052 DOI: 10.3389/fendo.2024.1304547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 02/01/2024] [Indexed: 03/02/2024] Open
Abstract
In recent years, numerous experimental studies have underscored the pivotal role of soluble epoxide hydrolase (sEH) in renal diseases, demonstrating the reno-protective effects of sEH inhibitors. The nexus between sEH and renal-associated diseases has garnered escalating attention. This review endeavors to elucidate the potential molecular mechanisms of sEH in renal diseases and emphasize the critical role of sEH inhibitors as a prospective treatment modality. Initially, we expound upon the correlation between sEH and Epoxyeicosatrienoic acids (EETs) and also addressing the impact of sEH on other epoxy fatty acids, delineate prevalent EPHX2 single nucleotide polymorphisms (SNPs) associated with renal diseases, and delve into sEH-mediated potential mechanisms, encompassing oxidative stress, inflammation, ER stress, and autophagy. Subsequently, we delineate clinical research pertaining to sEH inhibition or co-inhibition of sEH with other inhibitors for the regulation of renal-associated diseases, covering conditions such as acute kidney injury, chronic kidney diseases, diabetic nephropathy, and hypertension-induced renal injury. Our objective is to validate the potential role of sEH inhibitors in the treatment of renal injuries. We contend that a comprehensive comprehension of the salient attributes of sEH, coupled with insights from clinical experiments, provides invaluable guidance for clinicians and presents promising therapeutic avenues for patients suffering from renal diseases.
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Affiliation(s)
| | - Yongtong Cao
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China
| | - Liang Ma
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China
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Sartorius V, Giuseppi A, Iacobelli S, Leroy-Terquem E, Vinit N, Heidet L, Blanc T, Stirnemann J, Kermorvant-Duchemin E, Lapillonne A. Post-obstructive diuresis after posterior urethral valve treatment in neonates: a retrospective cohort study. Pediatr Nephrol 2024; 39:505-511. [PMID: 37656311 DOI: 10.1007/s00467-023-06100-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/04/2023] [Accepted: 07/04/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. METHODS Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. RESULTS Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg-1.h-1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137-246] vs. 95 [77-125] µmol.l-1; p < 0.001) and urea (8.5 [5.2-12.2] vs. 4.1 [3.5-4.7] mmol.l-1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). CONCLUSIONS In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Victor Sartorius
- Department of Neonatal Intensive Care, AP-HP Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015, Paris, France.
- Université Paris Cité, Paris, France.
| | - Agnès Giuseppi
- Department of Neonatal Intensive Care, AP-HP Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015, Paris, France
| | - Silvia Iacobelli
- Department of Neonatal and Pediatric Intensive Care, CHU La Réunion, Saint-Pierre, France
| | - Elise Leroy-Terquem
- Department of Neonatal Intensive Care, AP-HP Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015, Paris, France
| | - Nicolas Vinit
- Université Paris Cité, Paris, France
- Department of Pediatric Surgery and Urology, AP-HP Hôpital Necker Enfants-Malades, Paris, France
| | - Laurence Heidet
- Université Paris Cité, Paris, France
- Department of Pediatric Nephrology, Reference Center for Inherited Renal Diseases (MARHEA), AP-HP Hôpital Necker Enfants-Malades, Paris, France
| | - Thomas Blanc
- Université Paris Cité, Paris, France
- Department of Pediatric Surgery and Urology, AP-HP Hôpital Necker Enfants-Malades, Paris, France
| | - Julien Stirnemann
- Université Paris Cité, Paris, France
- Department of Obstetrics and Fetal Medicine, AP-HP Hôpital Necker Enfants-Malades, Paris, France
| | - Elsa Kermorvant-Duchemin
- Department of Neonatal Intensive Care, AP-HP Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015, Paris, France
- Université Paris Cité, Paris, France
| | - Alexandre Lapillonne
- Department of Neonatal Intensive Care, AP-HP Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015, Paris, France
- Université Paris Cité, Paris, France
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Almazmomi MA, Esmat A, Naeem A. Acute Kidney Injury: Definition, Management, and Promising Therapeutic Target. Cureus 2023; 15:e51228. [PMID: 38283512 PMCID: PMC10821757 DOI: 10.7759/cureus.51228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2023] [Indexed: 01/30/2024] Open
Abstract
Acute kidney injury (AKI) is caused by a sudden loss of renal function, resulting in the build-up of waste products and a significant increase in mortality and morbidity. It is commonly diagnosed in critically ill patients, with its occurrence estimated at up to 50% in patients hospitalized in the intensive critical unit. Despite ongoing efforts, the death rate associated with AKI has remained high over the past half-century. Thus, it is critical to investigate novel therapy options for preventing the epidemic. Many studies have found that inflammation and Toll-like receptor-4 (TLR-4) activation have a significant role in the pathogenesis of AKI. Noteworthy, challenges in the search for efficient pharmacological therapy for AKI have arisen due to the multifaceted origin and complexity of the clinical history of people with the disease. This article focuses on kidney injury's epidemiology, risk factors, and pathophysiological processes. Specifically, it focuses on the role of TLRs especially type 4 in disease development.
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Affiliation(s)
- Meaad A Almazmomi
- Pharmaceutical Care Department, Ministry of National Guard - Health Affairs, Jeddah, SAU
- Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
| | - Ahmed Esmat
- Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
| | - Anjum Naeem
- Pharmaceutical Care Department, Ministry of National Guard - Health Affairs, Jeddah, SAU
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Habas E, Al Adab A, Arryes M, Alfitori G, Farfar K, Habas AM, Akbar RA, Rayani A, Habas E, Elzouki A. Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates. Cureus 2023; 15:e46737. [PMID: 38022248 PMCID: PMC10631488 DOI: 10.7759/cureus.46737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Chronic kidney disease (CKD) is caused by hypoxia in the renal tissue, leading to inflammation and increased migration of pathogenic cells. Studies showed that leukocytes directly sense hypoxia and respond by initiating gene transcription, encoding the 2-integrin adhesion molecules. Moreover, other mechanisms participate in hypoxia, including anemia. CKD-associated anemia is common, which induces and worsens hypoxia, contributing to CKD progression. Anemia correction can slow CKD progression, but it should be cautiously approached. In this comprehensive review, the underlying pathophysiology mechanisms and the impact of renal tissue hypoxia and anemia in CKD onset and progression will be reviewed and discussed in detail. Searching for the latest updates in PubMed Central, Medline, PubMed database, Google Scholar, and Google search engines were conducted for original studies, including cross-sectional studies, cohort studies, clinical trials, and review articles using different keywords, phrases, and texts such as "CKD progression, anemia in CKD, CKD, anemia effect on CKD progression, anemia effect on CKD progression, and hypoxia and CKD progression". Kidney tissue hypoxia and anemia have an impact on CKD onset and progression. Hypoxia causes nephron cell death, enhancing fibrosis by increasing interstitium protein deposition, inflammatory cell activation, and apoptosis. Severe anemia correction improves life quality and may delay CKD progression. Detection and avoidance of the risk factors of hypoxia prevent recurrent acute kidney injury (AKI) and reduce the CKD rate. A better understanding of kidney hypoxia would prevent AKI and CKD and lead to new therapeutic strategies.
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Affiliation(s)
| | - Aisha Al Adab
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | - Mehdi Arryes
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | | | | | - Ala M Habas
- Internal Medicine, Tripoli University, Tripoli, LBY
| | - Raza A Akbar
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | - Amnna Rayani
- Hemat-oncology Department, Pediatric Tripoli Hospital, Tripoli University, Tripoli, LBY
| | - Eshrak Habas
- Internal Medicine, Tripoli University, Tripoli, LBY
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11
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Misurac JM, Grinsell MM, Narus JH, Mason S, Kallash M, Andreoli SP. NSAID-associated acute kidney injury in hospitalized children - a prospective Pediatric Nephrology Research Consortium study. Pediatr Nephrol 2023; 38:3109-3116. [PMID: 36943469 DOI: 10.1007/s00467-023-05916-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 02/03/2023] [Accepted: 02/13/2023] [Indexed: 03/23/2023]
Abstract
BACKGROUND Acute kidney injury (AKI) in children has serious short-term and long-term consequences. We sought 1) to prospectively describe NSAID-associated AKI in hospitalized children; 2) to determine if NSAID-associated AKI was more severe in younger children < 5 years; and 3) to follow outcomes after hospitalization for NSAID-associated AKI. METHODS This was a prospective, multi-center study in hospitalized children 1 month to 18 years. Parents/guardians were given a brief questionnaire to determine the dosing, duration, and type of NSAIDs given. Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to stage AKI severity. Patients with other causes of AKI were excluded (e.g., other nephrotoxins, sepsis, malignancy, etc.). RESULTS We identified 25 patients with NSAID-associated AKI, accounting for 3.1% of AKI. All 25 had AKI upon hospital presentation. The median age was 15.5 years, and 20/25 (80%) had volume depletion. Median duration of NSAID use was 2 days, and 63% of patients took the normal recommended NSAID dose. Median hospital length of stay was 4 days, and none required dialysis. At the most recent estimated glomerular filtration rate (eGFR) after discharge (available in 17/25 patients), only 4/17 (24%) had eGFR ≥ 90 ml/min/1.73 m2, and 13/17 (76%) had eGFR 60 to < 90 ml/min/1.73 m2, indicative of abnormal kidney function. CONCLUSIONS NSAID-associated AKI usually occurs with recommended NSAID dosing in the setting of dehydration. Follow-up after AKI showed a substantial rate of CKD. Therefore, we recommend that NSAIDs should not be used in dehydrated children. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Jason M Misurac
- Division of Pediatric Nephrology, Dialysis, and Transplantation, University of Iowa Stead Family Children's Hospital, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
- Department of Pediatrics, Pediatric Nephrology, Indiana University Medical Center, Indianapolis, IN, USA.
| | - Matthew M Grinsell
- Division of Pediatric Nephrology, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA
| | - JoAnn Hansen Narus
- Division of Pediatric Nephrology, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA
| | - Sherene Mason
- Division of Pediatric Nephrology, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Mahmoud Kallash
- Division of Pediatric Nephrology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Sharon P Andreoli
- Department of Pediatrics, Pediatric Nephrology, Indiana University Medical Center, Indianapolis, IN, USA
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12
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Abuduwupuer Z, Lei Q, Liang S, Xu F, Liang D, Yang X, Liu X, Zeng C. The Spectrum of Biopsy-Proven Kidney Diseases, Causes, and Renal Outcomes in Acute Kidney Injury Patients. Nephron Clin Pract 2023; 147:541-549. [PMID: 37094563 DOI: 10.1159/000530615] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/19/2023] [Indexed: 04/26/2023] Open
Abstract
INTRODUCTION Acute kidney injury (AKI) is a group of highly heterogeneous, complicated clinical syndromes. Although kidney biopsy plays an irreplaceable role in evaluating complex AKI, a few studies have focused on the clinicopathology of AKI biopsies. This study analyzed the pathological disease spectrum, causes, and renal outcomes of biopsied AKI patients. METHODS We retrospectively included 2,027 AKI patients who underwent kidney biopsies at a national clinical research center of kidney diseases from 2013 through 2018. To compare the biopsied AKI cases without and with coexisting glomerulopathy, patients were classified into acute tubular/tubulointerstitial nephropathy-associated AKI (ATIN-AKI) and glomerular disease-associated AKI (GD-AKI) groups. RESULTS Of 2,027 biopsied AKI patients, 65.1% were male, with a median age of 43 years. A total of 1,590 (78.4%) patients had coexisting GD, while only 437 (21.6%) patients had ATIN alone. The AKI patients with GD mainly (53.5%) manifested as stage 1 AKI, while most ATIN-AKI patients (74.8%) had stage 3 AKI. In the ATIN-AKI group, 256 (58.6%) patients had acute interstitial nephritis (AIN), and 77 (17.6%) had acute tubular injury (ATI). ATIN-AKI was mainly caused by drugs in 85.5% of AIN and 63.6% of ATI cases, respectively. In AKI patients with coexisting GD, the leading pathological diagnoses in over 80% of patients were IgA nephropathy (IgAN, 22.5%), minimal change disease (MCD, 17.5%), focal segmental glomerulosclerosis (FSGS, 15.3%), lupus nephritis (LN, 11.9%), membranous nephropathy (MN, 10.2%), and ANCA-associated vasculitis (AAV, 4.7%). A total of 775 patients were followed up within 3 months after renal biopsy; ATIN-AKI patients achieved statistically higher complete renal recovery than the GD-AKI patients (83.5% vs. 70.5%, p < 0.001). CONCLUSIONS Most biopsied AKI patients have coexisting GD, while ATIN alone is seen less frequently. ATIN-AKI is mainly caused by drugs. In GD-AKI patients, IgAN, MCD, FSGS, LN, MN, and AAV are the leading diagnoses. Compared to AKI patients without GD, patients with GD suffer from worse renal function recovery.
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Affiliation(s)
- Zulihumaer Abuduwupuer
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Qunjuan Lei
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Shaoshan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Feng Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Dandan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xue Yang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Xumeng Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Caihong Zeng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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13
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Li L, Zhu Q, Wang Z, Tao Y, Liu H, Tang F, Liu SM, Zhang Y. Establishment and validation of a predictive nomogram for gestational diabetes mellitus during early pregnancy term: A retrospective study. Front Endocrinol (Lausanne) 2023; 14:1087994. [PMID: 36909340 PMCID: PMC9998988 DOI: 10.3389/fendo.2023.1087994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 01/26/2023] [Indexed: 02/26/2023] Open
Abstract
Objective This study aims to develop and evaluate a predictive nomogram for early assessment risk factors of gestational diabetes mellitus (GDM) during early pregnancy term, so as to help early clinical management and intervention. Methods A total of 824 pregnant women at Zhongnan Hospital of Wuhan University and Maternal and Child Health Hospital of Hubei Province from 1 February 2020 to 30 April 2020 were enrolled in a retrospective observational study and comprised the training dataset. Routine clinical and laboratory information was collected; we applied least absolute shrinkage and selection operator (LASSO) logistic regression and multivariate ROC risk analysis to determine significant predictors and establish the nomogram, and the early pregnancy files (gestational weeks 12-16, n = 392) at the same hospital were collected as a validation dataset. We evaluated the nomogram via the receiver operating characteristic (ROC) curve, C-index, calibration curve, and decision curve analysis (DCA). Results We conducted LASSO analysis and multivariate regression to establish a GDM nomogram during the early pregnancy term; the five selected risk predictors are as follows: age, blood urea nitrogen (BUN), fibrinogen-to-albumin ratio (FAR), blood urea nitrogen-to-creatinine ratio (BUN/Cr), and blood urea nitrogen-to-albumin ratio (BUN/ALB). The calibration curve and DCA present optimal predictive power. DCA demonstrates that the nomogram could be applied clinically. Conclusion An effective nomogram that predicts GDM should be established in order to help clinical management and intervention at the early gestational stage.
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Affiliation(s)
- Luman Li
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan University, Wuhan, China
| | - Quan Zhu
- Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zihan Wang
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan University, Wuhan, China
| | - Yun Tao
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan University, Wuhan, China
| | - Huanyu Liu
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan University, Wuhan, China
| | - Fei Tang
- Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Song-Mei Liu
- Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory Zhongnan Hospital Wuhan University, Wuhan, China
| | - Yuanzhen Zhang
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan University, Wuhan, China
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Ansari L, Mahdinezhad MR, Rakhshandeh H, Hosseini A, Noughabi SB, Gholami N, Rajabian A. Acute and sub-acute toxicity assessment of the standardized extract of Sanguisorba minor in vivo. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2022; 19:987-997. [PMID: 34881541 DOI: 10.1515/jcim-2021-0391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/15/2021] [Indexed: 06/13/2023]
Abstract
Although Sanguisorba minor has been used as herbal medicine, no study has ever examined its potential toxicity. This study investigated acute and subacute toxicities of S. minor hydroalcoholic extract (SE). In the acute toxicity test, a single oral dose (300, 2,000, and 3,000 mg/kg) of SE was given to mice. The oral administration of SE (100, 200, and 400 mg/kg for 4 weeks) was performed to evaluate subacute toxicity. After the treatments, neurobehavioral, histopathology, hematological, and biochemical parameters were monitored. In vitro cytotoxicity was also assessed. Moreover, high-performance liquid chromatography fingerprint was done for the standardization of SE. The no-observed-adverse-effect level of SE was up to 2,000 mg/kg, and the LD50 of the prepared extract was over 3,000 mg/kg. The rats exposed to the extract did not show any marked change in their body weight. The extract at used doses did not affect neuromuscular coordination. According to the hematological, biochemical, and histological examinations, no significant treatment-related adverse effect of the extract was observed, even at 400 mg/kg. Only 48 h exposure to 400 μg/mL of SE reduced the viability of PC12 cells. The findings revealed that this plant could be well-tolerated, regarded safe, and used as herbal medicine.
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Affiliation(s)
- Legha Ansari
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Reza Mahdinezhad
- Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hassan Rakhshandeh
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Azar Hosseini
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Samaneh Boroumand Noughabi
- Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Najibeh Gholami
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arezoo Rajabian
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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15
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Stenson EK, Kendrick J, Dixon B, Thurman JM. The complement system in pediatric acute kidney injury. Pediatr Nephrol 2022; 38:1411-1425. [PMID: 36203104 PMCID: PMC9540254 DOI: 10.1007/s00467-022-05755-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/08/2022] [Accepted: 09/09/2022] [Indexed: 10/24/2022]
Abstract
The complement cascade is an important part of the innate immune system. In addition to helping the body to eliminate pathogens, however, complement activation also contributes to the pathogenesis of a wide range of kidney diseases. Recent work has revealed that uncontrolled complement activation is the key driver of several rare kidney diseases in children, including atypical hemolytic uremic syndrome and C3 glomerulopathy. In addition, a growing body of literature has implicated complement in the pathogenesis of more common kidney diseases, including acute kidney injury (AKI). Complement-targeted therapeutics are in use for a variety of diseases, and an increasing number of therapeutic agents are under development. With the implication of complement in the pathogenesis of AKI, complement-targeted therapeutics could be trialed to prevent or treat this condition. In this review, we discuss the evidence that the complement system is activated in pediatric patients with AKI, and we review the role of complement proteins as biomarkers and therapeutic targets in patients with AKI.
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Affiliation(s)
- Erin K. Stenson
- grid.430503.10000 0001 0703 675XSection of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, 13121 E 17th Avenue, MS8414, Aurora, CO 80045 USA
| | - Jessica Kendrick
- grid.430503.10000 0001 0703 675XDivision of Renal Disease and Hypertension, Department of Medicine, University of Colorado School of Medicine, Aurora, CO USA
| | - Bradley Dixon
- grid.430503.10000 0001 0703 675XRenal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO USA
| | - Joshua M. Thurman
- grid.430503.10000 0001 0703 675XDivision of Renal Disease and Hypertension, Department of Medicine, University of Colorado School of Medicine, Aurora, CO USA
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16
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Ruas AFL, Lébeis GM, de Castro NB, Palmeira VA, Costa LB, Lanza K, Simões E Silva AC. Acute kidney injury in pediatrics: an overview focusing on pathophysiology. Pediatr Nephrol 2022; 37:2037-2052. [PMID: 34845510 DOI: 10.1007/s00467-021-05346-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 01/12/2023]
Abstract
Acute kidney injury (AKI) is defined as an abrupt decline in glomerular filtration rate, with increased serum creatinine and nitrogenous waste products due to several possible etiologies. Incidence in the pediatric population is estimated to be 3.9 per 1,000 hospitalizations, and prevalence among children admitted to intensive care units is 26.9%. Despite being a condition with important incidence and morbimortality, further evidence on pathophysiology and management among the pediatric population is still lacking. This narrative review aimed to summarize and discuss current data on AKI pathophysiology in the pediatric population, considering all the physiological particularities of this age range and common etiologies. Additionally, we reported current diagnostic tools, novel biomarkers, and newly proposed medications that have been studied with the aim of early diagnosis and appropriate treatment of AKI in the future.
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Affiliation(s)
- Ana Flávia Lima Ruas
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Gabriel Malheiros Lébeis
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Nicholas Bianco de Castro
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Vitória Andrade Palmeira
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Larissa Braga Costa
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Katharina Lanza
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil
| | - Ana Cristina Simões E Silva
- Interdisciplinary Laboratory of Medical Investigation, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, Number 190, 2nd floor, Room #281, Belo Horizonte, MG, 30130100, Brazil.
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Jiang YJ, Xi XM, Jia HM, Zheng X, Wang MP, Li WX. The attributable mortality of new-onset acute kidney injury among critically ill patients: a propensity-matched analysis based on a multicentre prospective cohort study. Int Urol Nephrol 2022; 54:1987-1994. [PMID: 34997454 PMCID: PMC9262803 DOI: 10.1007/s11255-021-03087-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 12/08/2021] [Indexed: 11/09/2022]
Abstract
PURPOSE This study aimed to evaluate the attributable mortality of new-onset acute kidney injury (AKI). METHODS The data in the present study were derived from a multi-center, prospective cohort study in China that was performed at 18 Chinese ICUs. A propensity-matched analysis was performed between matched patients with and without AKI selected from all eligible patients to estimate the attributable mortality of new-onset AKI. RESULTS A total of 2872 critically ill adult patients were eligible. The incidence of new-onset AKI was 29.1% (n = 837). After propensity score matching, 788 patients with AKI were matched 1:1 with 788 controls (patients without AKI). Thirty-day mortality was significantly higher among the patients with AKI than among their matched controls (25.5% versus 17.4%, p < 0.001). Subgroup analysis in terms of AKI classification showed that there was no significant difference (p = 0.509) in 30-day mortality between patients with stage 1 AKI and their matched controls. The attributable mortality values of stage 2 and stage 3 AKI were 12.4% [95% confidence interval (CI) 2.6-21.8%, p = 0.013] and 16.1% (95% CI 8.2-23.8%, p < 0.001), respectively. The attributable mortality of persistent AKI was 15.7% (95% CI 8.8-22.4%, p = 0.001), while no observable difference in 30-day mortality was identified between transient AKI patients and their matched non-AKI controls (p = 0.229). CONCLUSION The absolute excess 30-day mortality that is statistically attributable to new-onset AKI is substantial (8.1%) among general ICU patients. However, neither stage 1 AKI nor transient AKI increases 30-day mortality.
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Affiliation(s)
- Yi-Jia Jiang
- Department of Surgical Intensive Care Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020 China
| | - Xiu-Ming Xi
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Hui-Miao Jia
- Department of Surgical Intensive Care Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020 China
| | - Xi Zheng
- Department of Surgical Intensive Care Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020 China
| | - Mei-Ping Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Wen-Xiong Li
- Department of Surgical Intensive Care Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020 China
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Li W, Wang W, He X, Liao Z, Aierken A, Hua J, Wang Y, Lu D, Zhang S. Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther 2022; 13:379. [PMID: 35902973 PMCID: PMC9331582 DOI: 10.1186/s13287-022-03039-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 07/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI. METHODS The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEVs. RESULTS Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose, D-Glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats. CONCLUSIONS We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.
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Affiliation(s)
- Weihui Li
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China.,Xi'an Animal Hospital, Northwest A&F University, Xi'an, China
| | - Wei Wang
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China.,Xi'an Animal Hospital, Northwest A&F University, Xi'an, China
| | - Xin He
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China
| | - Zheng Liao
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China
| | - Aili Aierken
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China
| | - Jinlian Hua
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China
| | - Yan Wang
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China.
| | - Dezhang Lu
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China. .,Xi'an Animal Hospital, Northwest A&F University, Xi'an, China.
| | - Shiqiang Zhang
- College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, 712100, China. .,Xi'an Animal Hospital, Northwest A&F University, Xi'an, China.
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Asnake M, Henock A, Abayneh M, Getu S, Hailemariam S, Endalkachew B, Zerihun D. Acute interstitial nephritis with Prothionamide. SAGE Open Med Case Rep 2022; 10:2050313X221094076. [PMID: 35585853 PMCID: PMC9109270 DOI: 10.1177/2050313x221094076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 03/25/2022] [Indexed: 11/16/2022] Open
Abstract
Among drug-related complications, drug-related nephrotoxicity is the commonest. It is the cause for 7% of all drug-related toxicities among inpatients and accounts for 20% to 30% of acute renal failure. Acute interstitial nephritis is one of the drug-related adverse reactions and occurs due to a drug-related type 4 hypersensitivity reaction. In this case report, we reported acute interstitial nephritis that causes acute renal failure (acute kidney injury) in a patient taking Prothionamide therapy. This drug-related side effect had not been reported. In this case report, we report a patient who develops fatigability, rash, and intermittent fever after 14 days of taking the drug Prothionamide. The main aims of this case report are to use it as a pharmacovigilance report for drug-producing companies and to consider a further study on this side effect. It is also an alert for clinicians to consider this side effect when patients develop acute interstitial nephritis while taking Prothionamide.
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Affiliation(s)
- Molla Asnake
- School of Medicine, College of Health Sciences, Mizan-Tepi University, Mizan Teferi, Ethiopia
| | - Andualem Henock
- School of Public Health, College of Health Sciences, Mizan-Tepi University, Mizan Teferi, Ethiopia
| | - Menigistu Abayneh
- Department of Medical Laboratory Technology, College of Health Sciences, Mizan-Tepi University, Mizan Teferi, Ethiopia
| | - Shimelis Getu
- School of Medicine, College of Health Sciences, Wolkite University, Wolkite, Ethiopia
| | - Shewangizaw Hailemariam
- Department of Midwifery, College of Health Sciences, Mizan-Tepi University, Mizan Teferi, Ethiopia
| | - Biruk Endalkachew
- Department of Biomedical Science, College of Health Sciences, Mizan-Tepi University, Mizan Teferi, Ethiopia
| | - Dessalegn Zerihun
- USAID Eliminate TB Project, KNCV Tuberculosis Foundation, Hawassa, Ethiopia
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20
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Molitoris BA. Low-Flow Acute Kidney Injury: The Pathophysiology of Prerenal Azotemia, Abdominal Compartment Syndrome, and Obstructive Uropathy. Clin J Am Soc Nephrol 2022; 17:1039-1049. [PMID: 35584927 PMCID: PMC9269622 DOI: 10.2215/cjn.15341121] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
AKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.
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Affiliation(s)
- Bruce A Molitoris
- Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, and Department of Anatomy, Cell Biology and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana
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21
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Zahler D, Lee-Rozenfeld K, Itach T, Lupu L, Banai S, Shacham Y. Time is Kidney: Relation between Pain to Balloon Time and Acute Kidney Injury among ST Segment Elevation Patients Undergoing Primary Percutaneous intervention. Cardiorenal Med 2022; 12:55-60. [DOI: 10.1159/000523829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 02/10/2022] [Indexed: 11/19/2022] Open
Abstract
Background: Among ST segment elevation myocardial infarction (STEMI) early hemodynamic changes may result in acute kidney injury (AKI) even prior to primary percutaneous coronary intervention (PCI), however, no information to date is present regarding the association between pain to balloon (PBT) and AKI. We evaluated whether PBT predicts the risk of AKI among STEMI patients undergoing primary PCI.
Methods: Medical records of 2343 STEMI patients undergoing primary PCI were reviewed. Patients were stratified by PBT into 3 groups: ≤120, 121-360 and > 360 minutes. Patients' records were assessed for the occurrence of AKI (defined by the KDIGO criteria as serum creatinine elevation ≥ 0.3 mg/dl within 72 hours after admission).
Results: Mean age was 61 ± 13 years and 1919 (82%) were male. Patients having longer PBT had more AKI complicating the course of STEMI (7 % vs. 8 % vs. 13 %, p<0.001) and had significantly higher serum creatinine changes throughout hospitalization (0.08 mg/dl vs. 0.11 mg/dl vs.0.17 mg/dl p<0.001). In a multivariable logistic regression model each 1-hour increase in PBT was independently associated with a 2.2% increase in risk for AKI (OR 1.022, 95% CI 1.01-1.04, p=0.02).
Conclusion: Longer PBT may be an independent marker for the development of AKI in STEMI patients undergoing primary.
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22
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Guo L, Chen S, Ou L, Li S, Ye ZN, Liu HF. Disrupted Alpha-Ketoglutarate Homeostasis: Understanding Kidney Diseases from the View of Metabolism and Beyond. Diabetes Metab Syndr Obes 2022; 15:1961-1974. [PMID: 35783031 PMCID: PMC9248815 DOI: 10.2147/dmso.s369090] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/17/2022] [Indexed: 11/26/2022] Open
Abstract
Alpha-ketoglutarate (AKG) is a key intermediate of various metabolic pathways including tricarboxylic acid (TCA) cycle, anabolic and catabolic reactions of amino acids, and collagen biosynthesis. Meanwhile, AKG also participates in multiple signaling pathways related to cellular redox regulation, epigenetic processes, and inflammation response. Emerging evidence has shown that kidney diseases like diabetic nephropathy and renal ischemia/reperfusion injury are associated with metabolic disorders. In consistence with metabolic role of AKG, further metabolomics study demonstrated a dysregulated AKG level in kidney diseases. Intriguingly, earlier studies during the years of 1980s and 1990s indicated that AKG may benefit wound healing and surgery recovery. Recently, interests on AKG are arising again due to its protective roles on healthy ageing, which may shed light on developing novel therapeutic strategies against age-related diseases including renal diseases. This review will summarize the physiological and pathological properties of AKG, as well as the underlying molecular mechanisms, with a special emphasis on kidney diseases.
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Affiliation(s)
- Lijing Guo
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
| | - Shihua Chen
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
| | - Liping Ou
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
| | - Shangmei Li
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
| | - Zhen-Nan Ye
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Correspondence: Zhen-Nan Ye; Hua-Feng Liu, Email ;
| | - Hua-Feng Liu
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China
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23
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Sethi A, Ahmad M, Huma T, Ahmad W. Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity. Drug Deliv 2021; 28:1569-1584. [PMID: 34291722 PMCID: PMC8300936 DOI: 10.1080/10717544.2021.1944398] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/01/2021] [Accepted: 06/10/2021] [Indexed: 11/18/2022] Open
Abstract
To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230-550 nm), zeta potential (-15 to -18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12-59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R2 = 0.972-0.976, N = 0.326-0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).
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Affiliation(s)
- Aisha Sethi
- Faculty of Pharmacy and Alternative medicines, the Islamia University of Bahawalpur, Bahawalpur, Pakistan
- Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Mahmood Ahmad
- Faculty of Pharmacy and Alternative medicines, the Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | | | - Waqas Ahmad
- Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
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Toro-Pérez J, Rodrigo R. Contribution of oxidative stress in the mechanisms of postoperative complications and multiple organ dysfunction syndrome. Redox Rep 2021; 26:35-44. [PMID: 33622196 PMCID: PMC7906620 DOI: 10.1080/13510002.2021.1891808] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND The extent of the damage following surgery has been subject of study for several years. Numerous surgical complications can impact postoperative quality of life of patients and even can cause mortality. Although these complications are generally due to multifactorial mechanisms, oxidative stress plays a key pathophysiological role. Moreover, oxidative stress could be an unavoidable effect derived even from the surgical procedure itself. METHODS A systematic review was performed following an electronic search of Pubmed and ScienceDirect databases. Keywords such as sepsis, oxidative stress, organ dysfunction, antioxidants, outcomes in postoperative complications, among others, were used. Review articles were preferably used between the years 2015 onwards, not excluding older ones. RESULTS The vast majority point to the role of oxidative stress in generating greater damage and worse prognosis in postoperative patients without the necessary care and precautions, taking importance on the use of antioxidants to prevent this problem. DISCUSSIONS Oxidative stress represents a common final pathway related to pathological processes such as inflammation or ischemia-reperfusion, among others. The expression of greater severity of these complications can result in multiple organ dysfunction or sepsis. The aim of this study was to present an update of the role of oxidative stress on surgical postoperative complications.
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Affiliation(s)
| | - Ramón Rodrigo
- Molecular and Clinical Pharmacology Program, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
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25
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Pajenda S, Zawedde F, Kapps S, Wagner L, Schmidt A, Winnicki W, O’Connell D, Gerges D. Urinary C3 levels associated with sepsis and acute kidney injury-A pilot study. PLoS One 2021; 16:e0259777. [PMID: 34767613 PMCID: PMC8589214 DOI: 10.1371/journal.pone.0259777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 10/18/2021] [Indexed: 12/01/2022] Open
Abstract
Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine.
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Affiliation(s)
- Sahra Pajenda
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Florence Zawedde
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Sebastian Kapps
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Ludwig Wagner
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Alice Schmidt
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Winnicki
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David O’Connell
- School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland
| | - Daniela Gerges
- Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- * E-mail:
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26
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Casili G, Ardizzone A, Basilotta R, Lanza M, Filippone A, Paterniti I, Esposito E, Campolo M. The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia-Reperfusion. Int J Mol Sci 2021; 22:11886. [PMID: 34769337 PMCID: PMC8584363 DOI: 10.3390/ijms222111886] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/28/2021] [Accepted: 10/28/2021] [Indexed: 12/18/2022] Open
Abstract
Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson's trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R.
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Affiliation(s)
| | | | | | | | | | | | - Emanuela Esposito
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31-98166 Messina, Italy; (G.C.); (A.A.); (R.B.); (M.L.); (A.F.); (I.P.); (M.C.)
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27
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Zhang X, Agborbesong E, Li X. The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential. Int J Mol Sci 2021; 22:ijms222011253. [PMID: 34681922 PMCID: PMC8537003 DOI: 10.3390/ijms222011253] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/10/2021] [Accepted: 10/13/2021] [Indexed: 12/19/2022] Open
Abstract
Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, and cell differentiation and death. Mitochondrial dysfunction has been recognized as a contributor in many diseases. The kidney is an organ enriched in mitochondria and with high energy demand in the human body. Recent studies have been focusing on how mitochondrial dysfunction contributes to the pathogenesis of different forms of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has been linked to an increased risk of developing CKD. AKI and CKD have a broad clinical syndrome and a substantial impact on morbidity and mortality, encompassing various etiologies and representing important challenges for global public health. Renal mitochondrial disorders are a common feature of diverse forms of AKI and CKD, which result from defects in mitochondrial structure, dynamics, and biogenesis as well as crosstalk of mitochondria with other organelles. Persistent dysregulation of mitochondrial homeostasis in AKI and CKD affects diverse cellular pathways, leading to an increase in renal microvascular loss, oxidative stress, apoptosis, and eventually renal failure. It is important to understand the cellular and molecular events that govern mitochondria functions and pathophysiology in AKI and CKD, which should facilitate the development of novel therapeutic strategies. This review provides an overview of the molecular insights of the mitochondria and the specific pathogenic mechanisms of mitochondrial dysfunction in the progression of AKI, CKD, and AKI to CKD transition. We also discuss the possible beneficial effects of mitochondrial-targeted therapeutic agents for the treatment of mitochondrial dysfunction-mediated AKI and CKD, which may translate into therapeutic options to ameliorate renal injury and delay the progression of these kidney diseases.
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Affiliation(s)
- Xiaoqin Zhang
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA; (X.Z.); (E.A.)
- Department of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
| | - Ewud Agborbesong
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA; (X.Z.); (E.A.)
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
- Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Xiaogang Li
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA; (X.Z.); (E.A.)
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
- Correspondence: ; Tel.: +507-266-0110
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28
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Abstract
Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin-APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA-APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA-APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA-APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA-apelin-APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.
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Affiliation(s)
- Zheng Ma
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China
| | - Juan-Juan Song
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China
| | - Sara Martin
- Santa Rosa Family Medicine Residency, Santa Rosa, CA, 95403, USA
| | - Xin-Chun Yang
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
| | - Jiu-Chang Zhong
- Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
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29
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Jiang YJ, Xi XM, Jia HM, Zheng X, Wang MP, Li W, Li WX. Risk factors, clinical features and outcome of new-onset acute kidney injury among critically ill patients: a database analysis based on prospective cohort study. BMC Nephrol 2021; 22:289. [PMID: 34433442 PMCID: PMC8390222 DOI: 10.1186/s12882-021-02503-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 08/14/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) newly-emerged in intensive care unit (ICU), has not been thoroughly studied in previous researches, is likely to differ from AKI developed before ICU admission. This study aimed to evaluate the incidence, risk factors, clinical features and outcome of new-onset AKI in critically ill patients. METHODS The data of present study derived from a multicenter, prospective cohort study in17 Chinese ICUs (January 2014 - August 2015). The incidence, risk factors, clinical features and survival analysis of new-onset AKI were assessed. RESULTS A total of 3374 adult critically ill patients were eligible. The incidence of new-onset AKI was 30.0 % (n = 1012). Factors associated with a higher risk of new-onset AKI included coronary heart disease, hypertension, chronic liver disease, use of nephrotoxic drugs, sepsis, SOFA score, APACHEII score and use of vasopressors. The new-onset AKI was an independent risk factor for 28-day mortality (adjusted hazard ratio, 1.643; 95 % CI, 1.370-1.948; P < 0.001). 220 (21.7 %) patients received renal replacement therapy (RRT), 71 (32.3 %) of them were successfully weaning from RRT. More than half of the new-onset AKI were transient AKI (renal recovery within 48 h). There was no statistical relationship between transient AKI and 28-day mortality (hazard ratio, 1.406; 95 % CI, 0.840-1.304; P = 0.686), while persistent AKI (non-renal recovery within 48 h) was strongly associated with 28-day mortality (adjusted hazard ratio, 1.486; 95 % CI, 1.137-1.943; P < 0.001). CONCLUSIONS New-onset AKI is common in ICU patients and is associated with significantly higher 28-day mortality. Only persistent AKI, but not transient AKI is associated with significantly higher 28-day mortality.
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Affiliation(s)
- Yi-Jia Jiang
- Department of Surgical Intensive Critical Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, 100020 Beijing, China
| | - Xiu-Ming Xi
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Hui-Miao Jia
- Department of Surgical Intensive Critical Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, 100020 Beijing, China
| | - Xi Zheng
- Department of Surgical Intensive Critical Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, 100020 Beijing, China
| | - Mei-Ping Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Wen Li
- Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China
| | - Wen-Xiong Li
- Department of Surgical Intensive Critical Unit, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, 100020 Beijing, China
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30
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Lupuşoru M, Lupuşoru G, Ailincăi I, Frățilă G, Andronesi A, Micu E, Banu M, Costea R, Ismail G. Renal replacement therapy in cancer patients with acute kidney injury (Review). Exp Ther Med 2021; 22:864. [PMID: 34178137 PMCID: PMC8220659 DOI: 10.3892/etm.2021.10296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/20/2021] [Indexed: 12/23/2022] Open
Abstract
Cancer patients are at high risk for developing acute kidney injury (AKI), which is associated with increased morbidity and mortality in these patients. Despite the progress made in understanding the pathogenic mechanisms and etiology of AKI in these patients, the main prevention consists of avoiding medication and nephrotoxic agents such as non-steroidal anti-inflammatory drugs, contrast agents used in medical imaging and modulation of chemotherapy regimens; when prophylactic measures are overcome and renal impairment becomes unresponsive to treatment, renal replacement therapy (RRT) is required. There are several methods of RRT that can be utilized for patients with malignancies and acute renal impairment; the choice of treatment being based on the patient characteristics. The aim of this article is to review the literature data regarding the epidemiology and management of AKI in cancer patients, the extracorporeal techniques used, choice of the appropriate therapy and the optimal time of initiation, and also the dose-prognosis relationship.
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Affiliation(s)
- Mircea Lupuşoru
- Department of Physiology 1, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Gabriela Lupuşoru
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
- Department of Uronephrology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Ailincăi
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
| | - Georgiana Frățilă
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
| | - Andreea Andronesi
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
- Department of Uronephrology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Elena Micu
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
- Department of Uronephrology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mihaela Banu
- Department of Morphology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Radu Costea
- Department of General Surgery, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Gener Ismail
- Department of Physiology 1, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Nephrology, 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
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Hu C, Sun J, Zhang Z, Zhang H, Zhou Q, Xu J, Ling Z, Ouyang J. Parallel comparison of R.E.N.A.L., PADUA, and C-index scoring systems in predicting outcomes after partial nephrectomy: A systematic review and meta-analysis. Cancer Med 2021; 10:5062-5077. [PMID: 34258874 PMCID: PMC8335816 DOI: 10.1002/cam4.4047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/05/2021] [Accepted: 05/14/2021] [Indexed: 12/18/2022] Open
Abstract
Objective To parallelly compare the applicability of the radius, exophytic/endophytic, nearness, anterior/posterior, location nephrometry score (R.E.N.A.L.), the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA), and the centrality index (C‐index) scoring systems in predicting clinical outcomes after partial nephrectomy (PN). Methods We searched EMBASE, PubMed, Ovid, and Web of Science to perform a meta‐analysis examining the correlation coefficients between three nephrometry scores (NSs) and warm ischemia time (WIT), estimated blood loss (EBL), operation time (OT), length of stay (LOS), and absolute change in eGFR (ACE) up to 25 January 2021. Results In total, 13 studies including 1496 patients met the criteria for further analysis. Overall, all scoring systems had statistically significant correlations with the WIT, EBL, OT, ACE and LOS and ACE, except for the correlation between PADUA and LOS (r = 0.16 [−0.00, 0.31], p > 0.05). The C‐index had the strongest correlation with WIT (r = −0.35 [−0.43, −0.26], p < 0.05) and ACE (r = −0.29 [−0.48, −0.10], p < 0.05). Weak correlations were observed between OT as well as EBL and each scoring system. Publication bias was observed in PADUA score predicting ACE (p = 0.04) and high heterogeneity was found in some of our results. Conclusion Until now, this is the first meta‐analysis that parallelly compares these three scoring systems in predicting outcomes after PN. We found that all NSs showed a statistically significant correlation with WIT, EBL, OT, and ACE. Moreover, the C‐index scoring system is the best predictor of WIT and ACE. Due to the existence of publication bias and high heterogeneity, more well‐designed and large‐scale studies are warranted for validation. To our knowledge, this is the first meta‐analysis that parallelly compares these three scoring systems in predicting outcomes after PN. Overall, three scoring systems were significantly correlated with WIT, EBL, OT and ACE. Moreover, the C‐index scoring system outperformed R.E.N.A.L. and PADUA scoring systems in WIT and ACE.
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Affiliation(s)
- Can Hu
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiale Sun
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhiyu Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Haoyang Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qi Zhou
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiangnan Xu
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhixin Ling
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jun Ouyang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Ding M, Tolbert E, Birkenbach M, Akhlaghi F, Gohh R, Ghonem NS. Treprostinil, a prostacyclin analog, ameliorates renal ischemia-reperfusion injury: preclinical studies in a rat model of acute kidney injury. Nephrol Dial Transplant 2021; 36:257-266. [PMID: 33156922 DOI: 10.1093/ndt/gfaa236] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Renal ischemia-reperfusion injury (IRI) is a major factor causing acute kidney injury (AKI). No pharmacological treatments for prevention or amelioration of I/R-induced renal injury are available. Here we investigate the protective effects of treprostinil, a prostacyclin analog, against renal IRI in vivo. METHODS Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion for 1-168 h. Treprostinil (100 ng/kg/min) or placebo was administered subcutaneously for 18-24 h before ischemia. RESULTS Treatment with treprostinil both significantly reduced peak elevation and accelerated the return to baseline levels for serum creatinine and blood urea nitrogen versus I/R-placebo animals following IRI. I/R-treprostinil animals exhibited reduced histopathological features of tubular epithelial injury versus I/R-placebo animals. IRI resulted in a marked induction of messenger RNA coding for kidney injury biomarkers, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin and for pro-inflammatory cytokines chemokine (C-C motif) ligand 2, interleukin 1β, interleukin 6 and intracellular adhesion molecular 1 in animals treated with placebo only relative to sham controls. Upregulation of expression of all these genes was significantly suppressed by treprostinil. Treprostinil significantly suppressed the elevation in renal lipid peroxidation found in the I/R-placebo group at 1-h post-reperfusion. In addition, renal protein expression of cleaved poly(ADP-ribose) polymerase 1 and caspase-3, -8 and -9 in I/R-placebo animals was significantly inhibited by treprostinil. CONCLUSIONS This study demonstrates the efficacy of treprostinil in ameliorating I/R-induced AKI in rats by significantly improving renal function early post-reperfusion and by inhibiting renal inflammation and tubular epithelial apoptosis. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against IRI in vivo.
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Affiliation(s)
- Meiwen Ding
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Evelyn Tolbert
- Division of Renal Disease, Department of Medicine, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
| | - Mark Birkenbach
- Department of Pathology, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
| | - Fatemeh Akhlaghi
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
| | - Reginald Gohh
- Division of Organ Transplantation, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI, USA
| | - Nisanne S Ghonem
- Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
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K V, HV S, K S. Acute and sub-chronic toxicity evaluation of a standardized green coffee bean extract (CGA-7™) in Wistar albino rats. SAGE Open Med 2021; 9:2050312120984885. [PMID: 33708386 PMCID: PMC7907716 DOI: 10.1177/2050312120984885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 12/08/2020] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE Despite having numerous physiological benefits, toxicological assessment of green coffee beans is sparce. Here, we document the oral acute and sub-chronic toxicity of a standardized decaffeinated green coffee bean extract containing 50% chlorogenic acids (CGA-7™) in rats. METHODS We have performed a limit test at single oral dose of 2000 mg/kg to evaluate the acute toxicity in female Wistar rats. Furthermore, repeated dose 90-day toxicity study was conducted to assess the risk of long-term use of CGA-7. RESULT A 14-day observation revealed no clinical signs of toxicity or mortality in animals at 2000 mg/kg acute oral dose of CGA-7. The administration of 250, 500, and 1000 mg/kg CGA-7 showed significant alterations in some parameters such as food consumption, relative organ weights of brain and spleen, haematological and biochemical parameters compared to control. These changes were not consistent and dose-dependent throughout the study. Furthermore, the changes were within the physiological range and toxicologically insignificant. CGA-7 did not affect the normal metabolism and physiology of the animals up to 1000 mg/kg dose. Macroscopic and histological examination of organs did not reveal any organ toxicity. CONCLUSION Finally, the findings from this study suggest the safety of green coffee bean extract.
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Affiliation(s)
- Venkatakrishna K
- R&D Center for Excellence, Vidya Herbs Pvt Ltd, Bangalore, India
| | - Sudeep HV
- R&D Center for Excellence, Vidya Herbs Pvt Ltd, Bangalore, India
| | - Shyamprasad K
- R&D Center for Excellence, Vidya Herbs Pvt Ltd, Bangalore, India
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Behrens F, Holle J, Kuebler WM, Simmons S. Extracellular vesicles as regulators of kidney function and disease. Intensive Care Med Exp 2020; 8:22. [PMID: 33336297 PMCID: PMC7746786 DOI: 10.1186/s40635-020-00306-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 05/21/2020] [Indexed: 12/16/2022] Open
Abstract
Extracellular vesicles (EVs) are small, lipid bilayer-delimited particles of cellular origin that recently gained increasing attention for their potential use as diagnostic biomarkers, and beyond that for their role in intercellular communication and as regulators of homeostatic and disease processes. In acute kidney injury (AKI) and chronic kidney disease (CKD), the potential use of EVs as diagnostic and prognostic markers has been evaluated in a series of clinical studies and contributions to pathophysiologic pathways have been investigated in experimental models. While EV concentrations in biofluids could not distinguish renal patients from healthy subjects or determine disease progression, specific EV subpopulations have been identified that may provide useful diagnostic and prognostic tools in AKI. Specific EV subpopulations are also associated with clinical complications in sepsis-induced AKI and in CKD. Beyond their role as biomarkers, pathophysiologic involvement of EVs has been shown in hemolytic uremic syndrome- and sepsis-induced AKI as well as in cardiovascular complications of CKD. On the other hand, some endogenously formed or therapeutically applied EVs demonstrate protective effects pointing toward their usefulness as emerging treatment strategy in kidney disease.
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Affiliation(s)
- Felix Behrens
- Institute of Physiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.,Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Johannes Holle
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Wolfgang M Kuebler
- Institute of Physiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. .,DZHK (German Centre for Cardiovascular Research), partner site Berlin, 10117, Berlin, Germany. .,The Keenan Research Centre for Biomedical Science at St. Michael's, Toronto, Canada. .,Departments of Surgery and Physiology, University of Toronto, Toronto, Canada.
| | - Szandor Simmons
- Institute of Physiology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.,DZHK (German Centre for Cardiovascular Research), partner site Berlin, 10117, Berlin, Germany
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Using electronic AKI alerts to define the epidemiology of acute kidney injury in renal transplants. J Nephrol 2020; 34:829-838. [PMID: 33259046 PMCID: PMC8192326 DOI: 10.1007/s40620-020-00869-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 09/16/2020] [Indexed: 01/18/2023]
Abstract
Background Little is known regarding the impact of acute kidney injury (AKI) on renal transplant outcome. Our aim was to define the incidence and outcome of AKI in renal transplant patients using data collected from a national AKI electronic alert system Methods The study represents a prospective national cohort study collecting data on 1224 renal transplants recipients with a functioning renal transplant, between April 2015 and March 2019. Results Four hundred forty patients experienced at least one episode of AKI giving an incidence rate of 35.4%. Sixty-four point seven% of episodes were AKI stage 1, 7.3% AKI stage 2 and 28% AKI stage 3. Only 6.2% of episodes occurred in the context of rejection. Forty-three point five% of AKI episodes were associated with sepsis. AKI was associated with pre-existing renal dysfunction, and a primary renal diagnosis of diabetic nephropathy. AKI was more prevalent in recipients from a donor after cardiac death (26.4% vs. 21.4%, p < 0.05) compared to the non-AKI cohort. Following AKI, 30-day mortality was 19.8% and overall mortality was 34.8%, compared to 8.4% in the non AKI cohort (RR 4.06, 95% CI 3.1–5.3, p < 0.001). Graft survival (GS), and death censored graft survival (DCGS) censored at 4 years, in the AKI cohort were significantly lower than in the non AKI group (p < 0.0001 for GS and DCGS). Conclusion The study provides a detailed characterisation of AKI in renal transplant recipients highlighting its significant negative impact on patient and graft survival.
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Pajenda S, Figurek A, Wagner L, Gerges D, Schmidt A, Herkner H, Winnicki W. Heparin-binding protein as a novel biomarker for sepsis-related acute kidney injury. PeerJ 2020; 8:e10122. [PMID: 33088624 PMCID: PMC7568480 DOI: 10.7717/peerj.10122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 09/16/2020] [Indexed: 12/20/2022] Open
Abstract
Background Sepsis-related acute kidney injury (AKI) is associated with high morbidity and mortality among patients. Underlying pathomechanisms include capillary leakage and fluid loss into the interstitial tissue and constant exposure to pathogens results in activation of inflammatory cascades, organ dysfunction and subsequently organ damage. Methods To identify novel factors that trigger sepsis-related acute kidney injury, plasma levels of Granzyme A, as representative of a lymphocyte-derived protease, and heparin-binding protein as indicator for neutrophil-derived mediators, were investigated retrospectively in 60 sepsis patients. Results While no association was found between plasma levels of lymphocyte-derived Granzyme A and the incidence of sepsis-related AKI, sepsis patients with AKI had significantly higher plasma levels of heparin-binding protein compared to those without AKI. This applies both to heparin-binding protein peak values (43.30 ± 23.34 vs. 30.25 ± 15.63 pg/mL; p = 0.005) as well as mean values (27.93 ± 14.39 vs. 22.02 ± 7.65 pg/mL; p = 0.021). Furthermore, a heparin-binding protein cut-off value of 23.89 pg/mL was established for AKI diagnosis. Conclusion This study identifies the neutrophil-derived heparin-binding protein as a valuable new biomarker for AKI in sepsis. Beyond the diagnostic perspective, this offers prospect for further research on pathogenesis of AKI and novel therapeutic approaches.
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Affiliation(s)
- Sahra Pajenda
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Andreja Figurek
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Ludwig Wagner
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Daniela Gerges
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Alice Schmidt
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Harald Herkner
- Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Winnicki
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
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Ntchapda F, Bonabe C, Atsamo AD, Kemeta Azambou DR, Bekono Fouda Y, Imar Djibrine S, Seke Etet PF, Théophile D. Effect of Aqueous Extract of Adansonia digitata Stem Bark on the Development of Hypertension in L-NAME-Induced Hypertensive Rat Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:3678469. [PMID: 33014103 PMCID: PMC7519996 DOI: 10.1155/2020/3678469] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 08/23/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Adansonia digitata is a plant used against cardiovascular disorders in African folk medicine. We assessed the effects of the aqueous extract of its stem bark on the development of hypertension in L-NAME-induced hypertensive rats. METHODS The animals were administered L-NAME once daily for 3 weeks (25 mg/kg, i.p.), concomitantly with aqueous extract of A. digitata stem bark (100 and 200 mg/kg, p.o.) or captopril (20 mg/kg, p.o.). Then, hemodynamic and electrocardiographic parameters, oxidative stress markers, and the lipid profile were assessed in the blood and heart, aorta, and kidney homogenates, and histopathological analyses were performed. RESULTS L-NAME-induced hypertensive control animals, but not the animals concomitantly treated with A. digitata extract, displayed increases in the mean arterial blood pressure (21.64% difference, p < 0.001, vs. dose 200 mg/kg), systolic arterial blood pressure (21.33%, p < 0.001), and the diastolic arterial blood pressure (21.84%, p < 0.001). In addition, hypertensive control animals displayed (i) increases in serum triglycerides, total cholesterol, LDL, and creatinine levels, malondialdehyde and transaminase activities, and atherogenic index; (ii) decreases in serum HDL, catalase, reduced glutathione, and nitric oxide; and (iii) aorta wall thickening, inflammatory cell infiltration, and cell loss in the cardiac muscle and renal tissues. As captopril, the extract prevented hypertension-like changes in lipid profile, cardiac, hepatic, and renal affection indicators, and oxidative stress markers. CONCLUSION Our findings suggest that the extract of A. digitata has antihypertensive and antioxidant effects in L-NAME-induced hypertension rat models. These effects partly justify the traditional medicine use against cardiovascular disorders.
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Affiliation(s)
- Fidèle Ntchapda
- Department of Biological Sciences, Faculty of Sciences, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon
| | - Christian Bonabe
- Department of Biological Sciences, Faculty of Sciences, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon
| | - Albert Donatien Atsamo
- Department of Animal Biology and Physiology, Laboratory of Animal Physiology, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon
| | - David Romain Kemeta Azambou
- Department of Biological Sciences, Faculty of Sciences, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon
| | - Yannick Bekono Fouda
- Department of Animal Biology and Physiology, Laboratory of Animal Physiology, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon
| | - Soudy Imar Djibrine
- Institut Universitaire des Sciences et Techniques d'Abéché (IUSTA), P.O. Box 6077, N'Djamena, Chad
| | - Paul F. Seke Etet
- Department of Physiological Sciences and Biochemistry, FMBS, University of Ngaoundéré, Ngaoundéré, P.O. Box 454, Cameroon
| | - Dimo Théophile
- Department of Animal Biology and Physiology, Laboratory of Animal Physiology, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon
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Therapeutic Potential of Selenium as a Component of Preservation Solutions for Kidney Transplantation. Molecules 2020; 25:molecules25163592. [PMID: 32784639 PMCID: PMC7463670 DOI: 10.3390/molecules25163592] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 07/28/2020] [Accepted: 08/05/2020] [Indexed: 01/23/2023] Open
Abstract
Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol® (modified Biolasol®), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se4+ ions at a dose of 1 µg/L into the Biolasol® preservation solution in the form of Na2SeO3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO32−) during ischemia/reperfusion.
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de Lima WV, Visona I, Schor N, Almeida WS. Preconditioning by aerobic exercise reduces acute ischemic renal injury in rats. Physiol Rep 2020; 7:e14176. [PMID: 31325250 PMCID: PMC6642274 DOI: 10.14814/phy2.14176] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 06/12/2019] [Accepted: 06/12/2019] [Indexed: 12/29/2022] Open
Abstract
Acute kidney injury (AKI) can be defined as the sudden loss of renal function associated with structural changes in the kidneys. Currently, 13.3 million people die of AKI around the world. Normally aerobic exercise is used both as/for the treatment and prevention of high blood pressure, metabolic disease and Diabetes mellitus (DM). Nevertheless, exercise preconditioning must be a crucial resource in the prevention and mitigation of AKI. The aim of this study was to evaluate the effects of the exercise preconditioning on renal IR (ischemic/reperfusion) experimental model. Male Wistars rats were divided into three groups (n = 9): sham (S), ischemic/reperfusion (IR), exercise + ischemic/reperfusion (EX + IR). IR renal injury was induced by clamping the bilateral renal artery for 45 min. The rats were subjected to exercise 5 days a week for 4 weeks with progressive intensity and duration. The group treated with exercise preconditioning, showed additional improvements in various parameters, including serum creatinine, proteinuria, and decrease of the severity of the tubular injury and activated caspase‐3 levels (P < 0.05). The previous aerobic exercise‐induced renoprotection in the IR injury. We anticipate that the practice of physical exercise in healthy individuals can also be useful for the prevention and attenuation of AKI.
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Affiliation(s)
- Weslei V de Lima
- Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP-EPM), São Paulo, SP, Brasil
| | - Iria Visona
- Pathology Department, Federal University of São Paulo (UNIFESP-EPM), São Paulo, SP, Brasil
| | - Nestor Schor
- Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP-EPM), São Paulo, SP, Brasil
| | - Waldemar S Almeida
- Nephrology Division, Department of Medicine, Federal University of São Paulo (UNIFESP-EPM), São Paulo, SP, Brasil
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Prognostic Factors for All-Cause Mortality in Thai Patients with Fragility Fracture of Hip: Comorbidities and Laboratory Evaluations. ACTA ACUST UNITED AC 2020; 56:medicina56060311. [PMID: 32599880 PMCID: PMC7353872 DOI: 10.3390/medicina56060311] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 06/18/2020] [Accepted: 06/22/2020] [Indexed: 12/31/2022]
Abstract
Background and Objectives: Although the types of comorbidities and laboratory evaluations are major factors associated with mortality after hip fractures, there have been no studies of the association of these factors and mortality in Thai hip-fracture patients. This study aimed to identify prognostic factors associated with mortality after a hip fracture in the Thai population, including types of comorbidities, treatment-related factors, and laboratory evaluations. Materials and Methods: This five-year retrospective study was conducted in a tertiary care hospital in Thailand. A total of 775 Thai patients who had been admitted with a hip fracture resulting from a simple fall were identified using the International Classification of Disease 10 codes, and a review of their medical charts was conducted. Associations between general factors, comorbidities, laboratory evaluations, treatment factors including type of treatment, and time to death were analyzed using the Cox proportional hazard regression and the hazard ratio (HR). Results: The overall mortality rate of hip fracture patients was 13.94%. Independent prognostic factors found to be significantly associated with mortality were nonoperative treatment (HR = 3.29, p < 0.001), admission glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 (HR = 3.40, p < 0.001), admission hemoglobin concentration <10 g/dL. (HR = 2.31, p < 0.001), chronic obstructive pulmonary disorder (HR = 2.63, p < 0.001), dementia or Alzheimer’s disease (HR = 4.06, p < 0.001), and active malignancy (HR = 6.80, p < 0.001). Conclusion: The types of comorbidities and laboratory evaluation findings associated with mortality in Thai patients with hip fractures include chronic obstructive pulmonary disorder, dementia or Alzheimer’s disease, active malignancy, admission GFR < 30 mL/min/1.73 m2, and admission hemoglobin concentration <10 g/dL. The risks of mortality for Thai hip-fracture patients with these comorbidities or laboratory evaluation findings were 2.5, 4, 7, 3.5, and 2.5 times higher, respectively, than patients without those factors.
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Shang Y, Madduma Hewage S, Wijerathne CUB, Siow YL, Isaak CK, O K. Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response. Front Med (Lausanne) 2020; 7:201. [PMID: 32582723 PMCID: PMC7280447 DOI: 10.3389/fmed.2020.00201] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/24/2020] [Indexed: 12/20/2022] Open
Abstract
Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are not fully understood. Inflammatory response plays an important role in IR-induced tissue injury. Although increased proinflammatory cytokines have been detected in the kidney and the distant organs after renal IR, their original sources remain uncertain. In the present study, we investigated the acute effect of renal IR on hepatic inflammatory cytokine expression and the mechanism involved. Sprague-Dawley rats that were subjected to renal IR (ischemia for 45 min followed by reperfusion for 1 h or 6 h) had increased plasma levels of creatinine, urea, and transaminases, indicating kidney and liver injuries. There was a significant increase in the expression of proinflammatory cytokine mRNA (MCP-1, TNF-α, IL-6) in the kidney and liver in rats with renal IR. This was accompanied by a significant increase in proinflammatory cytokine protein levels in the plasma, kidney, and liver. Activation of a nuclear transcription factor kappa B (NF-κB) was detected in the liver after renal IR. The inflammatory foci and an increased myeloperoxidase (MPO) activity were detected in the liver after renal IR, indicating hepatic inflammatory response and leukocyte infiltration. These results suggest that renal IR can directly activate NF-κB and induce acute production of proinflammatory cytokines in the liver. Renal IR-induced hepatic inflammatory response may contribute to impaired liver function and systemic inflammation.
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Affiliation(s)
- Yue Shang
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada
| | - Susara Madduma Hewage
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada
| | - Charith U B Wijerathne
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada
| | - Yaw L Siow
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.,Agriculture and Agri Food Canada, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada
| | - Cara K Isaak
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada
| | - Karmin O
- St. Boniface Hospital Research Centre, Winnipeg, MB, Canada.,Department of Animal Science, University of Manitoba, Winnipeg, MB, Canada.,Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada
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42
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Zhang Y, Li C, Guan C, Zhou B, Wang L, Yang C, Zhen L, Dai J, Zhao L, Jiang W, Xu Y. MiR-181d-5p Targets KLF6 to Improve Ischemia/Reperfusion-Induced AKI Through Effects on Renal Function, Apoptosis, and Inflammation. Front Physiol 2020; 11:510. [PMID: 32581828 PMCID: PMC7295155 DOI: 10.3389/fphys.2020.00510] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
Renal tubular epithelial cell (RTEC) death and renal interstitial inflammation are the most crucial pathophysiological changes in acute kidney ischemia/reperfusion injury (IRI). The microRNA (miR)-181d family plays diverse roles in cell proliferation, apoptosis and inflammation, but its renal target and potential role in IRI are unknown. Here, we showed that the expression of miR-181d-5p decreased and Krueppel-like factor 6 (KLF6) increased in a renal cell (HK-2) model of hypoxia/reoxygenation (H/R) injury and a mouse model of renal IRI. They were mainly distributed in the renal tubules. After renal IRI, miR-181d-5p overexpression significantly inhibited inflammatory mediators, reduced apoptosis and further improved renal function. KLF6 exacerbated RTEC damage and acted as a NF-κB co-activator to aggravate the renal IRI inflammatory response. Mechanistically, KLF6 was predicted as a new potential target gene of miR-181d-5p through bioinformatic analysis and luciferase reporter assay verification. After overexpressing miR-181d-5p and inhibiting KLF6, the role of miR-181d-5p was weakened on the renal damage improvement. In conclusion, miR-181d-5p upregulation produced protective antiapoptotic and anti-inflammatory effects against IRI in kidneys in vivo and H/R injury in HK-2 cells in vitro, and these effects were achieved by targeted inhibition of KLF6. Thus, our results provide novel insights into the molecular mechanisms associated with IRI and a potential novel therapeutic target.
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Affiliation(s)
- Yue Zhang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chenyu Li
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Nephrologisches Zentrum, Ludwig Maximilian University of Munich, Munich, Germany
| | - Chen Guan
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bin Zhou
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lin Wang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chengyu Yang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Li Zhen
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jie Dai
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Long Zhao
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wei Jiang
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yan Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
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43
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Tetta C, Deregibus MC, Camussi G. Stem cells and stem cell-derived extracellular vesicles in acute and chronic kidney diseases: mechanisms of repair. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:570. [PMID: 32775371 PMCID: PMC7347774 DOI: 10.21037/atm.2020.03.19] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Acute and chronic renal failure have long been described and now renamed as acute kidney injury (AKI) and chronic kidney disease (CKD). New concepts are emerging in the pathophysiology of kidney diseases. AKI is often caused by triggering factors (e.g., toxic, ischemic, immunologic) either individually or combined such as in sepsis (inflammation and hypoxia), and it is initiated at a defined time. Several experimental models of AKI have provided deep insight and have convincingly shown important proof-of-concepts of therapeutic relevance over the years. CKD is now considered a slowly developing disease with often an insidious course, lasting many years whereby co-morbidities (e.g., diabetes, hypertension, dysmetabolic syndrome) may act as worsening factors. It has become increasingly evident that even a single event of AKI may lead to a higher predisposition to develop a progressive CKD. In the present review, we will report studies on the renal protection by adult stem cells in different experimental models and clinical trials. The emerging role of extracellular vesicles (EVs) in cell-to-cell communication and their predominant effect in the paracrine mechanisms of stem cell-dependent actions have prompted several studies on their ability to attenuate both AKI and fibrosis occurring in CKD. We discuss several critical issues that need to be addressed before EVs may have a therapeutic application in humans.
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Affiliation(s)
- Ciro Tetta
- Unicyte Srl, University of Turin, Turin, Italy
| | - Maria Chiara Deregibus
- Department of Medical Sciences, University of Turin, Turin, Italy.,2i3T Incubator and Technology Transfer, University of Turin, Turin, Italy
| | - Giovanni Camussi
- Department of Medical Sciences, University of Turin, Turin, Italy
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44
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Shinzato T, Ohara K, Kaminaga H, Sugase T, Masuda T, Nagata D, Saki K, Kinoshita Y, Kubo T, Shimizu T, Nanmoku K, Yagisawa T. Acute Interstitial Nephritis and Acute Tubular Injury Due to a Transdermal Loxoprofen Patch. Intern Med 2020; 59:2733-2736. [PMID: 33132307 PMCID: PMC7691042 DOI: 10.2169/internalmedicine.4945-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.
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Affiliation(s)
- Takahiro Shinzato
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Ken Ohara
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University Hospital, Japan
| | - Hiroaki Kaminaga
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University Hospital, Japan
| | - Taro Sugase
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University Hospital, Japan
| | - Takahiro Masuda
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University Hospital, Japan
| | - Daisuke Nagata
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University Hospital, Japan
| | - Katano Saki
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Yoshitaka Kinoshita
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Taro Kubo
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Toshihiro Shimizu
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Koji Nanmoku
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
| | - Takashi Yagisawa
- Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Japan
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Aglae C, Muller L, Reboul P, Cariou S, Saber Davide B, Trusson R, Messikh Z, De Brauwere DP, Lefrant JY, Moranne O. Heterogeneity of Cause, Care, and Prognosis in Severe Acute Kidney Injury in Hospitalized Patients: A Prospective Observational Study. Can J Kidney Health Dis 2019; 6:2054358119892174. [PMID: 31839974 PMCID: PMC6896136 DOI: 10.1177/2054358119892174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 10/24/2019] [Indexed: 12/13/2022] Open
Abstract
Background: KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations. Objective: To describe severe AKI heterogeneity by department of hospitalization. Design: This is a prospective observational single-center study. Setting: Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017. Patients: All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 μmol/L. Measurements: Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI. Methods: A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others. Results: The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards. Limitations: We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery. Conclusion: Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.
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Affiliation(s)
- Cedric Aglae
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Laurent Muller
- Service des Réanimation, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Pascal Reboul
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Sylvain Cariou
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Barbar Saber Davide
- Service des Réanimation, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Remi Trusson
- Service des Réanimation, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Ziyad Messikh
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - David-Paul De Brauwere
- Service de Biochimie et Biologie Moléculaire, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Jean-Yves Lefrant
- Service des Réanimation, CHU Carémeau, Université de Montpellier-Nîmes, France
| | - Olivier Moranne
- Service Nephrologie-Dialyse-Aphérèse, CHU Carémeau, Université de Montpellier-Nîmes, France
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Bamoulid J, Philippot H, Kazory A, Yannaraki M, Crepin T, Vivet B, Devillard N, Roubiou C, Bresson-Vautrin C, Chalopin JM, Courivaud C, Ducloux D. Acute kidney injury in non-critical care setting: elaboration and validation of an in-hospital death prognosis score. BMC Nephrol 2019; 20:419. [PMID: 31752723 PMCID: PMC6868787 DOI: 10.1186/s12882-019-1610-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 10/29/2019] [Indexed: 01/05/2023] Open
Abstract
Background Acute kidney injury (AKI) is still characterized by a high mortality rate. While most patients with AKI are admitted in conventional medical units, current available data are still obtained from studies designed for patients admitted in intensive care units (ICU). Our study aimed to elaborate and validate an in-hospital death prognosis score for AKI admitted in conventional medical care units. Methods We included two prospective cohorts of consecutive patients with AKI admitted between 2001 and 2004 (elaboration cohort (EC)) and between 2010 and 2014 (validation cohort (VC)). We developed a scoring system from clinical and biological parameters recorded at admission from the EC to predict in-hospital mortality. This score was then tested for validation in the VC. Results Three-hundred and twenty-three and 534 patients were included in the EC and VC cohorts, respectively. The proportion of in-hospital death were 15.5% (EC) and 8.9% (VC), mainly due to sepsis. The parameters independently associated with the in-hospital death in the EC were Glasgow score, oxygen requirement, fluid overload, blood diastolic pressure, multiple myeloma and prothrombin time. The in-hospital death prognosis score AUC was 0.845 +/− 0.297 (p < 0.001) after validation in the VC. Conclusions Our in-hospital death prognosis score is the first to be prospectively developed and validated for AKI admitted in a conventional medical care unit. Based on current parameters, easily collected at time of admission, this score could be a useful tool for physicians and nephrologists to determine the in-hospital death prognosis of this AKI population.
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Affiliation(s)
- Jamal Bamoulid
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France. .,UMR1098, Federation hospitalo-universitaire INCREASE, F-25020, Besançon, France. .,Faculté de Médecine et de Pharmacie, Université de Franche-Comté, F-25020, Besançon, France. .,Structure Fédérative de Recherche, SFR FED4234, F-25000, Besançon, France.
| | - Hélène Philippot
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France.
| | - Amir Kazory
- Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - Maria Yannaraki
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France
| | - Thomas Crepin
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France.,UMR1098, Federation hospitalo-universitaire INCREASE, F-25020, Besançon, France.,Faculté de Médecine et de Pharmacie, Université de Franche-Comté, F-25020, Besançon, France.,Structure Fédérative de Recherche, SFR FED4234, F-25000, Besançon, France
| | - Bérengère Vivet
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France
| | - Nadège Devillard
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France
| | - Caroline Roubiou
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France
| | - Catherine Bresson-Vautrin
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France
| | - Jean-Marc Chalopin
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France.,UMR1098, Federation hospitalo-universitaire INCREASE, F-25020, Besançon, France.,Faculté de Médecine et de Pharmacie, Université de Franche-Comté, F-25020, Besançon, France.,Structure Fédérative de Recherche, SFR FED4234, F-25000, Besançon, France
| | - Cécile Courivaud
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France.,UMR1098, Federation hospitalo-universitaire INCREASE, F-25020, Besançon, France.,Faculté de Médecine et de Pharmacie, Université de Franche-Comté, F-25020, Besançon, France.,Structure Fédérative de Recherche, SFR FED4234, F-25000, Besançon, France
| | - Didier Ducloux
- CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25030, Besançon, France.,UMR1098, Federation hospitalo-universitaire INCREASE, F-25020, Besançon, France.,Faculté de Médecine et de Pharmacie, Université de Franche-Comté, F-25020, Besançon, France.,Structure Fédérative de Recherche, SFR FED4234, F-25000, Besançon, France
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Lulekal E, Tesfaye S, Gebrechristos S, Dires K, Zenebe T, Zegeye N, Feleke G, Kassahun A, Shiferaw Y, Mekonnen A. Phytochemical analysis and evaluation of skin irritation, acute and sub-acute toxicity of Cymbopogon citratus essential oil in mice and rabbits. Toxicol Rep 2019; 6:1289-1294. [PMID: 31867219 PMCID: PMC6906703 DOI: 10.1016/j.toxrep.2019.11.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Revised: 10/22/2019] [Accepted: 11/01/2019] [Indexed: 11/20/2022] Open
Abstract
C. citrates essential oil contains about 71.297 % citral. 10 % ointment formulation of C. citratus oils did not cause skin irritation. Oral LD50 of C. citratus essential oil was greater than 2000 mg/kg. C. citratus essential oil didn’t produce any toxicity sign. No histopathological changes were detected in the organs tested. Cymbopogon citratus has been used by the local people in Ankober district, northern Ethiopia, as traditional medicine to treat various ailments. Its essential oil has been shown to have antibacterial, antifungal, antiprotozoal, anti-carcinogenic, anti-inflammatory and antioxidant activities amongst others. This study was conducted to determine skin irritation, acute and subacute toxicity of C. citratus essential oil in mice and rabbits. The essential oil was analyzed using GC–MS. The essential oil at dose of 2000 mg/kg body weight was administered to mice for 21 consecutive days. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were taken after sacrifice for gross findings and histological analyses. 10 % ointment formulation of C. citratus oils was applied on the rabbit skin to determine skin irritation effects. The result revealed, the presence of citral (71.297%), myrcene (19.034%), 4, 5-epoxycarene (2.780%), linalool (1.713%), ((S)-cis-verbenol (1.110 %), linalool (1.713 %), ((S)-cis-verbenol (1.110 %) and undecan-2-one (1.001 %) in the C. citratus essential oil. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control. No histopathological changes were detected in the organs tested. 10 % ointment formulation of C. citratus oils did not cause skin irritation. Analysis of results leads to the conclusion that Ethiopian C. citratus essential oil may be considered as relatively safe and non-toxic.
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Affiliation(s)
- Ermias Lulekal
- College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, P.O. Box 34731, Ethiopia
| | - Solomon Tesfaye
- College of Veterinary Medicine, Gigjiga University, Gigjiga, Ethiopia
| | - Selam Gebrechristos
- College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Kassahun Dires
- College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Tizazu Zenebe
- College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Nigus Zegeye
- College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Gezu Feleke
- College of Natural and Computational Sciences, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Abayneh Kassahun
- College of Natural and Computational Sciences, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Yoseph Shiferaw
- College of Natural and Computational Sciences, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
| | - Awol Mekonnen
- College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia
- Corresponding author at: College of Medicine, Debre Berhan University, Debre Berhan, P.O. Box 445, Ethiopia.
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48
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Armaly Z, Artol S, Jabbour AR, Saffouri A, Habashi N, Abd Elkadir A, Ghattas N, Farah R, Kinaneh S, Nseir W. Impact of pretreatment with carnitine and tadalafil on contrast-induced nephropathy in CKD patients. Ren Fail 2019; 41:976-986. [PMID: 31797710 PMCID: PMC6913644 DOI: 10.1080/0886022x.2019.1669459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 08/08/2019] [Accepted: 08/08/2019] [Indexed: 12/23/2022] Open
Abstract
Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.
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Affiliation(s)
- Zaher Armaly
- Department of Nephrology, E.M.M.S. Hospital, and Azrieli Faculty of Medicine in Galilee, Bar- Ilan University, Zafed, Israel
| | - Suheil Artol
- Department of Radiology, E.M.M.S. Hospital, Nazareth, Israel
| | | | - Amer Saffouri
- Department of Internal Medicine, E.M.M.S. Hospital, Nazareth, Israel
| | - Nayef Habashi
- Department of Nephrology, HaEmeq Hospital Afula, Afula, Israel
| | - Amir Abd Elkadir
- Department of Nephrology, E.M.M.S. Hospital, and Azrieli Faculty of Medicine in Galilee, Bar- Ilan University, Zafed, Israel
| | - Naser Ghattas
- Department of Internal Medicine, The Western Galilee Hospital, Nahariya, Israel
| | - Raymond Farah
- Department of Internal Medicine “B”, Ziv Medical Center, and Azrieli Faculty of Medicine in Galilee, Bar- Ilan University, Zafed, Israel.
| | - Safa Kinaneh
- Department of Nephrology, E.M.M.S. Hospital, and Azrieli Faculty of Medicine in Galilee, Bar- Ilan University, Zafed, Israel
| | - William Nseir
- Department of Internal Medicine, E.M.M.S. Hospital, Nazareth, Israel
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49
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Faria J, Ahmed S, Gerritsen KGF, Mihaila SM, Masereeuw R. Kidney-based in vitro models for drug-induced toxicity testing. Arch Toxicol 2019; 93:3397-3418. [PMID: 31664498 DOI: 10.1007/s00204-019-02598-0] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/15/2019] [Indexed: 12/18/2022]
Abstract
The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs' microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.
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Affiliation(s)
- João Faria
- Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands
| | - Sabbir Ahmed
- Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands
| | - Karin G F Gerritsen
- Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands
| | - Silvia M Mihaila
- Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.,Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands
| | - Rosalinde Masereeuw
- Division of Pharmacology, Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
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Fathima N, Kashif T, Janapala RN, Jayaraj JS, Qaseem A. Single-best Choice Between Intermittent Versus Continuous Renal Replacement Therapy: A Review. Cureus 2019; 11:e5558. [PMID: 31695978 PMCID: PMC6820322 DOI: 10.7759/cureus.5558] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 09/02/2019] [Indexed: 11/06/2022] Open
Abstract
Critically ill patients often develop multiorgan dysfunction syndrome. Acute kidney injury (AKI) is part of it. Renal replacement therapy (RRT) remains the primary choice of treatment in severely ill patients who develop AKI. Recent data have shown increased use of RRT in AKI patients. Therefore, the right choice of RRT plays an important role in the renal recovery of such patients. The question of which mode of RRT to apply has been the topic of study in the last two decades. Whether RRT should be conducted in intermittent mode, as intermittent hemodialysis (IHD), or in continuous mode, as continuous renal replacement therapy (CRRT), is still being investigated. CRRT has a hypothetical advantage when compared to IHD, as it involves a process in which there is gradual removal of fluids, better control of urea, better maintenance of the acid/base balance, and hemodynamic stability. However, IHD is more practical, cost-effective, does not require anticoagulation, decreases the bleeding risk, and removes the solute efficiently and rapidly in acute life-threatening conditions. Other modalities of RRT like sustained low-efficiency daily dialysis (SLEDD) and prolonged intermittent renal replacement therapy (PIRRT) have shown to encompass the benefits of both CRRT in terms of hemodynamic stability and IHD in terms of cost-efficiency. Although SLEDD is progressively being used as an alternative to CRRT and IHD, very few studies have shown to support it. In this article, we try to summarize the advantages and disadvantages of the different techniques used in RRT. With SLEDD gaining more popularity among the different modalities of RRT, we want to assess the possibility of its routine implementation as the single-best choice for RRT.
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Affiliation(s)
- Nida Fathima
- Internal Medicine, Sri Siddhartha Medical College, Tumkur, IND
| | - Tooba Kashif
- Cardiology, Heart and Vascular Institute, Dearborn, USA
| | - Rajesh Naidu Janapala
- Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA
| | - Joseph S Jayaraj
- Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, USA
| | - Aisha Qaseem
- Internal Medicine, Emory Johns Creek Hospital, Georgia, USA
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