Renal Edema Research Articles

On the Application of Zhenwu Decoction in Renal Edema

On the Application of Zhenwu Decoction in Renal Edema

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

Protective effect of quercetin on cadmium-induced kidney apoptosis in rats based on PERK signaling pathway

BackgroundCadmium (Cd) is a highly toxic environmental pollutant that can enter the body through bioaccumulation. The kidney is an important target organ for Cd poisoning. Quercetin (Que) is a natural flavonoid compound with free radical scavenging and antioxidant properties. Previous studies showed that Que can alleviate kidney damage caused by Cd poisoning in rats, but the specific mechanism is still unclear. MethodsTwenty-four male Sprague–Dawley (SD) rats were divided into four groups: normal saline-treated control group, Cd group treated by intraperitoneal injection of 2 mg/kg b.w. CdCl2, Cd + Que group treated by intraperitoneal injection of 2 mg/kg b.w. CdCl2 and 100 mg/kg b.w. Que, and Que group treated by 100 mg/kg b.w. Que. Four weeks later, the rats were anesthetized with diethyl ether, and blood was taken intravenously. The rats were executed with their necks cut off, and the kidneys were removed. Body weight, kidney organ weight, and glutathione (GSH) and malondialdehyde (MDA) levels were measured. The structure of kidney tissue was observed by hematoxylin and eosin staining, kidney cell apoptosis was detected by TUNEL assay, and the mRNA expression levels of genes related to the PERK signaling pathway were analyzed by RT-PCR. ResultsCompared with the control group, the Cd-treated group exhibited a significant decrease in body weight (P < 0.01). Their kidneys showed a significant increase in the relative organ weight (P < 0.01). Moreover, the MDA and GSH levels increased. Kidney tissue damage and renal cell apoptosis were observed, and the mRNA expression levels of genes related to the PERK signaling pathway significantly increased (P < 0.01). Compared with the Cd-treated group, the Cd + Que group exhibited a significant increase in body weight (P < 0.01) and significant decreases in the relative organ weight, MDA and GSH levels, and mRNA expression levels of genes related to the PERK signaling pathway (P < 0.01). Furthermore, kidney tissue damage and renal cell apoptosis were observed. ConclusionCd treatment resulted in rat weight loss, renal edema, and oxidative stress and caused renal tissue damage and cell apoptosis by activating the PERK signaling pathway. Que was able to restore the body weight and renal coefficient of rats. It also alleviated the oxidative stress and kidney tissue damage caused by Cd and the cell apoptosis caused by Cd through inhibiting the PERK signaling pathway. Thus, Que could be considered for the treatment of kidney diseases caused by Cd poisoning.

Female sex protects against renal edema, but not lung edema, in mice with partial deletion of the endothelial barrier regulator Tie2 compared to male sex.

The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin/Tie2 system and edema formation. Adult male and female heterozygous Tie2 knockout mice (Tie2+/-) and wild-type controls (Tie2+/+) were included (n = 9 per group). Renal and pulmonary injury were determined by wet/dry weight ratio and H&E staining of tissue sections. Protein levels were studied in plasma by ELISA and pulmonary and renal mRNA expression levels by RT-qPCR. In Tie2+/+ mice, females had higher circulating angiopoietin-2 (138%, p<0.05) compared to males. Gene expression of angiopoietin-1 (204%, p<0.01), angiopoietin-2 (542%, p<0.001) were higher in females compared to males in kidneys, but not in lungs. Gene expression of Tie2, Tie1 and VE-PTP were similar between males and females in both organs. Renal and pulmonary wet/dry weight ratio did not differ between Tie2+/+ females and males. Tie2+/+ females had lower circulating NGAL (41%, p<0.01) compared to males, whereas renal NGAL and KIM1 gene expression was unaffected. Interestingly, male Tie2+/- mice had 28% higher renal wet/dry weight ratio (p<0.05) compared to Tie2+/+ males, which was not observed in females nor in lungs. Partial deletion of Tie2 did not affect circulating angiopoietin-1 or angiopoietin-2, but soluble Tie2 was 44% and 53% lower in males and females, respectively, compared to Tie2+/+ mice of the same sex. Renal and pulmonary gene expression of angiopoietin-1, angiopoietin-2, estrogen receptors and other endothelial barrier regulators was comparable between Tie2+/- and Tie2+/+ mice in both sexes. Female sex seems to protect against renal, but not pulmonary edema in heterozygous Tie2 knock-out mice. This could not be explained by sex dimorphism in the endothelial angiopoietin/Tie2 system.

Treatment of Renal Edema Based on TCM Syndrome Differentiation

Treatment of Renal Edema Based on TCM Syndrome Differentiation

Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra Naja haje Venom: A Comparative Study.

In Morocco, eight species of venomous snakes belonging to the Viperidae and Elapidae families are responsible for severe envenomation cases. The species from the Elapidae family is only represented by the medically relevant cobra Naja haje, which is widely distributed in North Africa. However, there is little information on the systemic effects of Moroccan cobra venom on vital organs due to regional variations. It has been demonstrated that the venom of Naja haje from Egypt causes hemorrhage, while the venom of the Moroccan cobra is neurotoxic and devoid of systemic bleeding. This variability is known to significantly influence treatment efficacy against Naja haje cobra bites in the Middle East. In this study, we examined the pathophysiological mechanisms responsible for the lethality induced by Naja haje venom, as well as the evaluation of the neutralizing capacity of two antivenoms; the monospecific antivenom made for Naja haje only and the antivenom marketed in the Middle East and North Africa. We first determined the toxicity of Naja haje venom by LD50 test, then compared the neutralizing capacity of the two antivenoms studied by determining the ED50. We also performed histological analysis on Swiss mice envenomed and treated with these antivenoms to observe signs of cobra venom envenomation and the degree of reduction of induced systemic alterations. The results showed significant differences between both antivenoms in terms of neutralization. The monospecific antivenom was four times more effective than the marketed antivenom. These results were confirmed by a histological study, which showed that monospecific antivenoms neutralized severe signs of mortality, such as congestion of blood vessels in the heart and kidneys, pulmonary and renal edema, cytoplasmic vacuolization of hepatocytes in the liver, and infiltration of inflammatory cells in the brain and spleen. However, the polyvalent antivenom failed to protect all severe lesions induced by Naja haje venom in mice. These findings highlight the negative impact of geographic variation on the effectiveness of conventional antivenom therapy and confirm the need for a specific Naja haje antivenom for the effective treatment of cobra envenomation in Morocco.

Decreased renal apparent diffusion coefficient after COVID-19 associated acute kidney injury

Study objective: To investigate if there are any differences in total renal blood flow, regional renal perfusion, renal oxygenation or renal tissue properties, studied by non-invasive MRI, in patients having recovered from severe COVID-19 with different grades of acute kidney injury (AKI). Hypothesis: We hypothesize that the decrease in renal blood flow and perfusion that our research group have previously found in severe COVID-19 patients with AKI 1 may persist together with possible renal edema and development of fibrosis. Material and methods: We identified patients with AKI grade 3 from a cohort of patients previously treated in the intensive care unit for severe COVID-19 with respiratory failure. These patients were matched to possible extent regarding age, sex, height, weight, body mass index (BMI) and body surface area (BSA) with patients from the same cohort that had AKI grade 1 and patients that did not have AKI. A total of 22 patients were included. Because of common occurrence of oliguria without a reduction of glomerular filtration, AKI grade was determined using the Kidney Disease Improving Global Outcome (KDIGO) creatinine criteria only. All patients had a record of a plasma creatinine inside normal range within two years prior to ICU care, and had no history of renal disease. Comorbidities were common in the study population. Follow up examination was performed approximately five months after the patients were admitted the ICU. Results: Significant differences in cortical and medullary ADC were demonstrated between the study groups. Both cortical and medullary ADC was significantly reduced in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and the ‘AKI grade 1’ group. Total renal blood flow was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and global renal perfusion was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ and ‘AKI grade 1’ groups. No significant differences in either cortical or medullary perfusion were seen between the groups. Cortical and medullary oxygenation and renal vein oxygen saturation did not differ significantly between the groups. Conclusion: In this study we demonstrates that, approximately five months after intensive care for severe COVID-19, patients that had high grades of AKI during hospitalization have reduced cortical and medullary ADC together with reduced total renal blood flow and global renal perfusion compared to similar patients that did not have AKI. These findings might indicate development of renal fibrosis. No differences regarding renal oxygenation were observed between the studied groups. 1. Luther T, Eckerbom P, Cox E, Lipcsey M, Bulow S, Hultstrom M, et al. Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study. Crit Care. 2022;26(1):262. Public and private funding sources. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Research progress in traditional Chinese and Western medicine for renal edema

Research progress in traditional Chinese and Western medicine for renal edema

MiR-181a-5p Inhibits Pyroptosis in Sepsis-Induced Acute Kidney Injury through Downregulation of NEK7.

Sepsis is a life-threatening organ dysfunction caused by the uncontrolled inflammation, easily affecting the kidney. Sepsis-induced acute kidney injury (S-AKI) has high morbidity and mortality, of which the pathophysiological mechanisms have not been completely illuminated, leading to nonspecific therapies. Specific microRNAs were related with the pathogenesis of AKI. However, only limited studies focused on the pyroptosis in the context of S-AKI. The in vitro LPS-induced HK-2 cell model and in vivo CLP-induced mouse model were established. qRT-PCR, Western blot, ELISA, and RNA pulldown were used for expression examination. Multiple biological databases were used for miRNA screening. H&E staining and IHC staining were performed. The LPS-induced HK-2 cells showed significantly increased (P < 0.01) fluorescence intensity of N-GSDMD and ASC compared with the HK-2 cells. The expression of NLRP3, NEK7, ASC, active caspase-1, and N-GSDMD was significantly enhanced (P < 0.05) and the inflammatory factors including IL-18, IL-1β, and THF-α were all increased in LPS-induced HK-2 cells and CLP-induced mice. Renal edema, serum Cr and BUN, and expression of KIM-1 and NGAL were significantly higher (P < 0.05) in CLP-induced S-AKI mice than the sham group. miR-101-3p, miR-144-3p, miR-181a-5p, miR-4262, and miR-513b-5p could inhibit NEK7. NEK7 is an interacting protein of miRNA-181a-5p. miR-181a-5p inhibits pyroptosis of the LPS-induced HK-2 cells through downregulation of NEK7. Pyroptosis of HK-2 cells promotes inflammation. miR-181a-5p inhibits pyroptosis through downregulation of NEK7 in LPS-induced HK-2 cells and CLP-induced mice. Our study indicated miR-181a-5p as a new potential therapeutic target for S-AKI therapy.

Aqueous Two-Phase Extraction, Antioxidant and Renal Protective Effects of Polysaccharides from Spores of Cordyceps cicadae

The aim of this study was to investigate the aqueous two-phase extraction (ATPE), in vitro antioxidant, and in vivo renal protective effects of polysaccharides from spores of Cordyceps cicadae (CCSPs). The optimal ATPE parameters were as follows: an extraction temperature of 61 °C, an ammonium sulfate concentration of 18%, an ethanol concentration of 40%, a liquid-to-material ratio of 33 mL/g, and an extraction time of 60 min. Under these parameters, the CCSPs yield was 6.96 ± 0.11% (n = 3), which was consistent with the predicted yield (6.92%). Among the three purified polysaccharide fractions, CCSP-2 displayed stronger scavenging activities against DPPH radicals and hydroxyl radicals, reducing power and ferrous-ion-chelating ability to a greater extent than CCSP-1 and CCSP-3. CCSP-2 exhibited its protective effect in lipopolysaccharide (LPS)-induced septic acute kidney injury (AKI) mice by significantly alleviating renal edema; reducing 24 h urine protein, blood urea nitrogen (BUN), and serum creatinine (SCr); inhibiting the release of serum proinflammatory cytokines; boosting the activities of antioxidant enzymes; and reducing the levels of oxidative damage products. These results suggest that CCSP-2 exerted its protective effect against LPS-induced septic AKI in mice through anti-inflammatory and antioxidant pathways.

Severe Pre-Eclampsia with Partial Hellp Syndrome in Multigravida Preterm Pregnancy

Preeclampsia is the second highest cause of maternal death in Indonesia. The incidence of preeclampsia in Indonesia is very high at 24%. West Java is a province in Indonesia with a high preeclampsia rate of 25%.Pre-eclampsia is a vascular endothelial dysfunction and vasospasm that occurs at gestational age above 20 months and is characterized by hypertension and proteinuria, with or without pathological edema. Severe preeclampsia (PEB) is characterized by a minimum of systolic blood pressure 160 mmHg or diastolic blood pressure 110, impaired liver function, progressive renal insufficiency, pulmonary edema, brain and visual disturbances, or thrombocytopenia. This research is descriptive observational with a case report approach. The aim of this research is to discuss updates on the occurrence, concept, pathophysiology, and management of preeclampsia. In the case reported, a female patient, aged 29 years G3P2A0, 36 weeks gestational age with severe pre-eclampsia, partial hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in a multigravida preterm pregnancy with grade I obesity and a history of cesarean section 5 years ago. After evaluation, the patient complained of headache and heartburn. After confirmation, the fetus has IUGR, then active management with Transperitoneal Sectio Caesarea is chosen.

Six Methods to Treat Renal Edema in Chinese Medicine

Edema is one of the typical symptoms of renal diseases in clinical practice, and the effective treatment of nephrogenic edema in Chinese medicine can be achieved. In this paper, we believe that the evidence of nephrogenic edema is a deficiency of the root cause and a deficiency of the lung, spleen and kidney as the pathogenesis. From the perspective of the combination of staging and classification, and the combination of strengthening the body and eliminating pathogens, it can be concluded that ① lift the pot and lift the lid, soothe the lungs and benefit water, ② remove the herbs, promote blood circulation and promote water, ③ nourish the spleen and strengthen the movement, warm the yang and benefit the water, ④ the spleen and kidney Shuangnuan, transforming qi and promoting water, ⑤ soothing the liver and reducing swelling, reconciling Shaoyang, ⑥ nourishing qi and nourishing blood, and diuretic and reducing swelling, in order to improve the theoretical support of traditional Chinese medicine for the treatment of renal edema.

Pathological, Immunological, and Hematological Parameters Associated with Experimental Infection of Citrobacter Freundii in Rabbits.

Citrobacter freundii is one of the most important nosocomial opportunistic pathogens, which causes sepsis, as well as different gross and histopathological lesions in various internal organs in humans and animals, especially dogs and fish. This study aimed to investigate the hematological parameters, immunological responses, and pathological effects of the infection induced by the virulent strain of C. freundii on rabbits. A total of 42 rabbits (local breed; male and female), with a mean weight of 1.5-2 kg, were housed under controlled environmental conditions (20±2°C, 14:10 h light: dark cycle) and allowed ad libitum access to food and water. After two weeks of adaption, the rabbits were divided randomly into three groups of 14 animals per group. Group one (G1) received 3×108 CFU/ml of the virulent isolate (intraperitoneally [IP]) of C. freundii. Group two (G2) was injected subcutaneously (SC) with 3×108 CFU/ml of the virulent strain of C. freundii, while group three was IP injected with phosphate buffer saline and considered a negative control group. Results showed the variable gross pathological effects which included hemorrhage, edema, and congestion of visceral organs. Furthermore, the microscopic lesions showed pneumonia due to inflammatory cells infiltration, mainly neutrophils, macrophages, plasmacytes, and lymphocytes, severe interstitial and intra-alveolar edema, extensive pulmonary hemorrhage, emphysema, and atelectasis. The recorded data from the liver samples revealed hepatitis which was characterized by perivascular and periportal leukocyte cuffing, marked centrilobular with periportal necrosis, extensive hepatic edema, and periportal edema in addition to extensive fibrosis in interlobular septa and periportal fibrosis with severe interstitial hemorrhage. In the kidneys, there were severe renal edema, mixed inflammatory exudation, mainly neutrophils, macrophages, plasmacytes, lymphocytes, fibroblast infiltration in renal parenchyma and renal cortex, extensive renal hemorrhage, edema, as well as fibrosis and severe renal tubular necrosis. In addition, enteritis appeared in the intestine with mucosal edema, especially in lamina propria; moreover, necrosis of entire villi, epithelial necrosis, mucosal and submucosal hemorrhage, and fibrosis were observed. The present study revealed a significant increase in total leukocytes count and the concentration of TNF-α in the infected groups. To the best of the authors' knowledge, this study is considered the first attempt aimed to detect the pathological effects of C. freundii on visceral organs in rabbits. It is concluded that this bacterium could induce a significant pathological, hematological, and immunological changes in the infected animals.

Massive Endoleak From Retro-Aortic Left Renal Vein Fistula

A 64 year old non-smoking man without concomitant disorders was admitted with sudden onset of abdominal pain and hypotension. Computed tomography angiography (CTA) showed a 90 mm infrarenal abdominal aortic aneurysm (AAA) with free retroperitoneal fluid. The AAA was treated as a rupture by endovascular repair. After re-evaluation of the pre-operative CTA, the retroperitoneal fluid was considered secondary to renal oedema caused by aorto-left renal vein (LRV) fistula. (A) Post-operative CTA showed a massive endoleak (arrow) through the fistula confirmed by phlebography (B, arrows). This was resolved by implanting a self expandable stent graft in the LRV.Image 1

Preservation of renal endothelial integrity and reduction of renal edema by aprotinin does not preserve renal perfusion and function following experimental cardiopulmonary bypass

BackgroundAcute kidney injury is a severe complication following cardiopulmonary bypass (CPB) and is associated with capillary leakage and microcirculatory perfusion disturbances. CPB-induced thrombin release results in capillary hyperpermeability via activation of protease-activated receptor 1 (PAR1). We investigated whether aprotinin, which is thought to prevent thrombin from activating PAR1, preserves renal endothelial structure, reduces renal edema and preserves renal perfusion and reduces renal injury following CPB.MethodsRats were subjected to CPB after treatment with 33.000 KIU/kg aprotinin (n = 15) or PBS (n = 15) as control. A secondary dose of 33.000 KIU/kg aprotinin was given 60 min after initiation of CPB. Cremaster and renal microcirculatory perfusion were assessed using intravital microscopy and contrast echography before CPB and 10 and 60 min after weaning from CPB. Renal edema was determined by wet/dry weight ratio and renal endothelial structure by electron microscopy. Renal PAR1 gene and protein expression and markers of renal injury were determined.ResultsCPB reduced cremaster microcirculatory perfusion by 2.5-fold (15 (10–16) to 6 (2–10) perfused microvessels, p < 0.0001) and renal perfusion by 1.6-fold (202 (67–599) to 129 (31–292) au/sec, p = 0.03) in control animals. Both did not restore 60 min post-CPB. This was paralleled by increased plasma creatinine (p < 0.01), neutrophil gelatinase-associated lipocalin (NGAL; p = 0.003) and kidney injury molecule-1 (KIM-1; p < 0.01). Aprotinin treatment preserved cremaster microcirculatory perfusion following CPB (12 (7–15) vs. 6 (2–10) perfused microvessels, p = 0.002), but not renal perfusion (96 (35–313) vs. 129 (31–292) au/s, p > 0.9) compared to untreated rats. Aprotinin treatment reduced endothelial gap formation (0.5 ± 0.5 vs. 3.1 ± 1.4 gaps, p < 0.0001), kidney wet/dry weight ratio (4.6 ± 0.2 vs. 4.4 ± 0.2, p = 0.046), and fluid requirements (3.9 ± 3.3 vs. 7.5 ± 3.0 ml, p = 0.006) compared to untreated rats. In addition, aprotinin treatment reduced tubulointerstitial neutrophil influx by 1.7-fold compared to untreated rats (30.7 ± 22.1 vs. 53.2 ± 17.2 neutrophil influx/section, p = 0.009). No differences were observed in renal PAR1 expression and plasma creatinine, NGAL or KIM-1 between groups.ConclusionsAprotinin did not improve renal perfusion nor reduce renal injury during the first hour following experimental CPB despite preservation of renal endothelial integrity and reduction of renal edema.

The role of miR-199b-3p in regulating Nrf2 pathway by dihydromyricetin to alleviate septic acute kidney injury

The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin–eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway.

387-P: Protective Impact and Potential Mechanisms of Elabela on DKD via ß-Arrestins

Objective: ELABELA (ELA), an endogenous ligand for apelin receptor (APJ), is decreased in plasma of DKD patients. The effects of ELA on relieving diabetic renal lesion have not been reported. This study was performed to explore the protective impact and potential mechanisms of ELA on DKD via β-arrestins. Methods: Sixteen eight-week-old male db/db mice were randomly divided into diabetic nephropathy group (db/db group) and intervention group (db/db+ELA group) with administration of ELA (5mg ∙ kg-1 ∙ day-1) for 8 weeks. 8 age-matched male db/m mice were recognized as normal control group (db/m group). Both db/db and db/m group received equivalent normal saline injection for 8 weeks. Body weights and blood glucose levels were measured once a week. After 8 weeks, blood and urine samples were collected. Serum creatinine and urinary albumin to creatinine ration (UACR) were examined. The kidneys were taken after sacrificing mice. The morphology change of kidney tissues were assessed by HE and PAS staining. The expression of β-Arrestin1/2 was detected by immunohistochemistry. The levels of fibronectin (FN), collagen type IV (Col-IV) and β-arrestin1/2 in kidney tissues were examined by western blotting. Results: (1) With the intervention of ELA, UACR, serum creatinine and the ratio of kidney weight to body weight of db/db mice were significantly decreased (P&amp;lt;0.05). (2) Compared with db/m mice, db/db mice exhibited renal tubular epithelial cells edema, decreased ratio of non-lumen area to total area, thickened basement membrane and increased glycogen accumulation, however, those pathological abnormality were mitigated by ELA. (3) The levels of FN, Col-IV and β-Arrestin-1/2 in db/db mice were higher than db/m mice, while ELA treatment suppressed the expression of FN, COL-IV and β-Arrestin-1/2 (P&amp;lt;0.05). Conclusions: ELA may play a role in protection from diabetic kidney damage via down-regulating the expression of β-Arrestin-1/2 and inhibiting the secretion of extracellular matrix. Disclosure M. Shi: None. Y. Chen: None. H. Zhang: None. Funding National Natural Science Foundation of China (81700723)

The effect of targeting Tie2 on hemorrhagic shock-induced renal perfusion disturbances in rats

BackgroundHemorrhagic shock is associated with acute kidney injury and increased mortality. Targeting the endothelial angiopoietin/Tie2 system, which regulates endothelial permeability, previously reduced hemorrhagic shock-induced vascular leakage. We hypothesized that as a consequence of vascular leakage, renal perfusion and function is impaired and that activating Tie2 restores renal perfusion and function.MethodsRats underwent 1 h of hemorrhagic shock and were treated with either vasculotide or PBS as control, followed by fluid resuscitation for 4 h. Microcirculatory perfusion was measured in the renal cortex and cremaster muscle using contrast echography and intravital microscopy, respectively. Changes in the angiopoietin/Tie2 system and renal injury markers were measured in plasma and on protein and mRNA level in renal tissue. Renal edema formation was determined by wet/dry weight ratios and renal structure by histological analysis.ResultsHemorrhagic shock significantly decreased renal perfusion (240 ± 138 to 51 ± 40, p < 0.0001) and cremaster perfusion (12 ± 2 to 5 ± 2 perfused vessels, p < 0.0001) compared to baseline values. Fluid resuscitation partially restored both perfusion parameters, but both remained below baseline values (renal perfusion 120 ± 58, p = 0.08, cremaster perfusion 7 ± 2 perfused vessels, p < 0.0001 compared to baseline). Hemorrhagic shock increased circulating angiopoietin-1 (p < 0.0001), angiopoietin-2 (p < 0.0001) and soluble Tie2 (p = 0.05), of which angiopoietin-2 elevation was associated with renal edema formation (r = 0.81, p < 0.0001). Hemorrhagic shock induced renal injury, as assessed by increased levels of plasma neutrophil gelatinase-associated lipocalin (NGAL: p < 0.05), kidney injury marker-1 (KIM-1; p < 0.01) and creatinine (p < 0.05). Vasculotide did not improve renal perfusion (p > 0.9 at all time points) or reduce renal injury (NGAL p = 0.26, KIM-1 p = 0.78, creatinine p > 0.9, renal edema p = 0.08), but temporarily improved cremaster perfusion at 3 h following start of fluid resuscitation compared to untreated rats (resuscitation + 3 h: 11 ± 3 vs 8 ± 3 perfused vessels, p < 0.05).ConclusionHemorrhagic shock-induced renal impairment cannot be restored by standard fluid resuscitation, nor by activation of Tie2. Future treatment strategies should focus on reducing angiopoietin-2 levels or on activating Tie2 via an alternative strategy.

Drug-induced peripheral oedema: An aetiology-based review.

Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of a drug.