scholarly journals Gender differences control the susceptibility to ER stress-induced acute kidney injury

2013 ◽  
Vol 304 (7) ◽  
pp. F875-F882 ◽  
Author(s):  
Rawad Hodeify ◽  
Judit Megyesi ◽  
Adel Tarcsafalvi ◽  
Hossam I. Mustafa ◽  
Nang San Hti Lar Seng ◽  
...  

Endoplasmic reticulum (ER) stress contributes to acute kidney injury induced by several causes. Kidney dysfunction was shown to be influenced by gender differences. In this study we observed differences in the severity of kidney injury between male and female mice in response to tunicamycin, an ER stress agent. Tunicamycin-treated male mice showed a severe decline in kidney function and extensive kidney damage of proximal tubules in the kidney outer cortex (S1 and S2 segments). Interestingly, female tunicamycin-treated mice did not show a decline in kidney function, and their kidneys showed damage localized primarily to proximal tubules in the inner cortex (S3 segment). Protein markers of ER stress, glucose-regulated protein, and X-box binding protein 1 were also more elevated in male mice. Similarly, the induction of apoptosis was higher in tunicamycin-treated male mice, as measured by the activation of Bax and caspase-3. Testosterone administered to female mice before tunicamycin resulted in a phenotype similar to male mice with a comparable decline in renal function, tissue morphology, and induction of ER stress markers. We conclude that kidneys of male mice are much more susceptible to ER stress-induced acute kidney injury than those of females. Moreover, this sexual dimorphism could provide an interesting model to study the relation between kidney function and injury to a specific nephron segment.

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle E. Soranno ◽  
Peter Baker ◽  
Lara Kirkbride-Romeo ◽  
Sara A. Wennersten ◽  
Kathy Ding ◽  
...  

AbstractAcute kidney injury (AKI) is common in patients, causes systemic sequelae, and predisposes patients to long-term cardiovascular disease. To date, studies of the effects of AKI on cardiovascular outcomes have only been performed in male mice. We recently demonstrated that male mice developed diastolic dysfunction, hypertension and reduced cardiac ATP levels versus sham 1 year after AKI. The effects of female sex on long-term cardiac outcomes after AKI are unknown. Therefore, we examined the 1-year cardiorenal outcomes following a single episode of bilateral renal ischemia–reperfusion injury in female C57BL/6 mice using a model with similar severity of AKI and performed concomitantly to recently published male cohorts. To match the severity of AKI between male and female mice, females received 34 min of ischemia time compared to 25 min in males. Serial renal function, echocardiograms and blood pressure assessments were performed throughout the 1-year study. Renal histology, and cardiac and plasma metabolomics and mitochondrial function in the heart and kidney were evaluated at 1 year. Measured glomerular filtration rates (GFR) were similar between male and female mice throughout the 1-year study period. One year after AKI, female mice had preserved diastolic function, normal blood pressure, and preserved levels of cardiac ATP. Compared to males, females demonstrated pathway enrichment in arginine metabolism and amino acid related energy production in both the heart and plasma, and glutathione in the plasma. Cardiac mitochondrial respiration in Complex I of the electron transport chain demonstrated improved mitochondrial function in females compared to males, regardless of AKI or sham. This is the first study to examine the long-term cardiac effects of AKI on female mice and indicate that there are important sex-related cardiorenal differences. The role of female sex in cardiovascular outcomes after AKI merits further investigation.


2021 ◽  
Vol 8 ◽  
pp. 205435812110180
Author(s):  
Orit Kliuk-Ben Bassat ◽  
Sapir Sadon ◽  
Svetlana Sirota ◽  
Arie Steinvil ◽  
Maayan Konigstein ◽  
...  

Background: Transcatheter aortic valve replacement (TAVR), although associated with an increased risk for acute kidney injury (AKI), may also result in improvement in renal function. Objective: The aim of this study is to evaluate the magnitude of kidney function improvement (KFI) after TAVR and to assess its significance on long-term mortality. Design: This is a prospective single center study. Setting: The study was conducted in cardiology department, interventional unit, in a tertiary hospital. Patients: The cohort included 1321 patients who underwent TAVR. Measurements: Serum creatinine level was measured at baseline, before the procedure, and over the next 7 days or until discharge. Methods: Kidney function improvement was defined as the mirror image of AKI, a reduction in pre-procedural to post-procedural minimal creatinine of more than 0.3 mg/dL, or a ratio of post-procedural minimal creatinine to pre-procedural creatinine of less than 0.66, up to 7 days after the procedure. Patients were categorized and compared for clinical endpoints according to post-procedural renal function change into 3 groups: KFI, AKI, or preserved kidney function (PKF). The primary endpoint was long-term all-cause mortality. Results: The incidence of KFI was 5%. In 55 out of 66 patients patients, the improvement in kidney function was minor and of unclear clinical significance. Acute kidney injury occurred in 19.1%. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 was a predictor of KFI after multivariable analysis (odds ratio = 0.93 to develop KFI; confidence interval [95% CI]: 0.91-0.95, P < .001). Patients in the KFI group had a higher Society of Thoracic Surgery (STS) score than other groups. Mortality rate did not differ between KFI group and PKF group (43.9% in KFI group and 33.8% in PKF group) but was significantly higher in the AKI group (60.7%, P < .001). Limitations: The following are the limitations: heterozygous definitions of KFI within different studies and a single center study. Although data were collected prospectively, analysis plan was defined after data collection. Conclusions: Improvement in kidney function following TAVR was not a common phenomenon in our cohort and did not reduce overall mortality rate.


Author(s):  
Ravindra Attur Prabhu ◽  
Tushar Shaw ◽  
Indu Ramachandra Rao ◽  
Vandana Kalwaje Eshwara ◽  
Shankar Prasad Nagaraju ◽  
...  

Abstract Background Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described. Aim This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis. Methods A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI. Results Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140–29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67–21.22, P < 0.001) and shock (OR 3.75; CI 1.63–8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66–68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15–21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9–13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92–24, P = 0.002) and stage 3 (OR 17.8, CI 5.05–62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%). Conclusions AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors. Graphic abstract


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sara Núñez Delgado ◽  
Miren Iriarte-Abril ◽  
Júlia Farrera-Núñez ◽  
Sergi Pascual-Sánchez ◽  
Laia Sans-Atxer ◽  
...  

Abstract Background and Aims Acute renal failure (AKI) associated to rhabdomyolysis conditions a worse prognosis in short-term, its implication in the long-term renal function has been less evaluated. Method Retrospective analysis of patients diagnosed with rhabdomyolysis defined by creatinine kinase &gt; 5000 IU/L between 2015-2019. Basal and 12-month renal function was evaluated. AKI was classified as either non-severe (AKI-KDIGO 1/2) or severe (AKI-KDIGO 3). Results Eighty-seven patients were included, 25 (28.74%) had some degree of chronic kidney disease (CKD) on admission. 56 (64.37%) had AKI on admission, 17 of which were severe (6 required hemodialysis). The patients with AKI had more cardiovascular disease (CVD) and worse analytical parameters on admission (table). Patients with severe AKI showed no difference in CVD from those with non-severe AKI but were younger and had more hyperkalemia. There were no significant differences between patients with severe AKI who required hemodialysis and those who did not. Inpatient mortality was 8%, higher in patients with AKI but without differences according to severity. In 45 patients kidney function was available 12 months after the episode, loss of eGF was -4.90 ± 14.35 ml/min-1.73m2 (p=0.007). There was no difference between patients who developed AKI and those who did not (-4.10 ± 14.4 vs. -5.39 ± 14.57 ml/min-1.73m2; p=0.67), nor between non-severe and severe AKI (-5.50 ± 14.76 vs. -5.12 ± 15.08ml/min-1.73m2; p=0.98). Of the 33 patients without previous CKD, 5 developed CKD, with greater decrease in eGF than those who did not (-22.69 ± 6.04 vs. -2.63 ± 13.92 ml/min-1.73m2; p=0.003). Female sex (60% vs. 12%; p=0.031) and previous basal eGF (72.22 ± 4.37 vs. 95.6±19.97 ml/min-1.72m2; p=0.016) were related to this deterioration. Conclusion After an episode of rhabdomyolysis, the loss of eGF is similar in patients who develop AKI compared to those who do not.


2006 ◽  
Vol 189 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yongmei Wang ◽  
Takeshi Sakata ◽  
Hashem Z Elalieh ◽  
Scott J Munson ◽  
Andrew Burghardt ◽  
...  

Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 μg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 μg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor κB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.


2020 ◽  
Author(s):  
Benedict Morath ◽  
Andreas Meid ◽  
Johannes Rickmann ◽  
Jasmin Soethoff ◽  
Markus Verch ◽  
...  

Abstract Background: Fluid management is an everyday challenge in intensive care units worldwide. Data from recent trials suggest that the use of hydroxyethyl starch leads to a higher rate of acute kidney injury and mortality in septic patients. Evidence on the safety of hydroxyethyl starch used in postoperative cardiac surgery patients is lacking Methods: The aim was to determine the impact of postoperatively administered hydroxyethylstarch 130/0.42 on renal function and 90-day mortality compared to with or without balanced crystalloids in patients after elective cardiac surgery. A retrospective cohort analysis was performed including 2245 patients undergoing elective coronary artery bypass grafting or, aortic valve replacement, or a combination of both between 2015 - 2019. Acute kidney injury was defined according to the ‘kidney disease improving global outcomes’ criteria. Multivariate logistic regression yielded adjusted associations of postoperative hydroxyethyl starch administration with acute kidney injury during hospital stay and 90-day mortality. Linear mixed-effects models predicted trajectories of estimated glomerular filtration rates over the postoperative period to explore the impact of dosage and timing of hydroxyethyl starch administration.Results: A total of 1009 patients (45.0 %) suffered from acute kidney injury. Significantly less acute kidney injury of any stage occurred in patients receiving hydroxyethyl starch compared to patients receiving only crystalloids for fluid resuscitation (43.7 % vs. 51.2 % p=0.008). In multivariate analysis, the administration of hydroxyethyl starch showed a protective effect (OR 0.89 95% confidence interval (CI) (0.82-0.96)) which was less prominent in patients receiving only crystalloids (OR 0.98, 95% CI (0.95-1.00)). No association between hydroxyethyl starch and 90-day mortality (OR 1.05 95% CI (0.88-1.25)) was detected. Renal function trajectories were dose-dependent and biphasic and hydroxyethyl starch could even slow down the late postoperative decline of kidney function.Conclusion: This study showed no association between hydroxyethyl starch and the postoperative occurrence of acute kidney injury and may add evidence to the discussion about the use of hydroxyethyl starch in cardiac surgery patients. In addition, hydroxyethyl starch administered early after surgery in adequate low doses might even prevent the decline of the kidney function after cardiac surgery.


Author(s):  
O. Gogayeva ◽  
V. Lazoryshynets ◽  
A. Rudenko ◽  
L. Dzakhoieva ◽  
O. Yuvchyk

The study aimed to analyze kidney function for patients with complicated forms of coronary artery disease (CAD) in the perioperative period. Methods. It was a retrospective analysis of 110 high-risk patients with complicated forms of CAD, who were operated on and discharged from the National M. Amosov Institute for the period from 2009 till 2019 years. Kidney function was evaluated by glomerular filtration rate (GFR), calculated online with СKD-EPI formula. Results. Among the included patients there were 86 (78.1%) patients with metabolic syndrome, 81 (73.59%) patients with disorders of glucose metabolism, 82 (74.5%) subjects with chronic obstructive pulmonary disease and 38 (34.5%) patients had chronic kidney disease (CKD) 3-5 stage. Preoperative risk stratification with EuroScore II scale was 9.4%. All operations performed in cardiopulmonary bypass; Custodial cardioplegia was used in 53 (48.1%) patients. The average perfusion time was 111 minutes, average cross-clamping time was 73.9 minutes. Acute kidney injury in the early postoperative period had 9 (8.1%) patients. Conclusions. At the admittance 38 (34.5%) patients with complicated forms of CAD had CKD 3-5 st. Analysis of the GFR dynamic in the early postoperative period shown a decrease in GFR in 71.05% of patients. Transient acute kidney injury with 50% sCr growth had 9 (8.1%) patients but didn’t require hemodialysis.


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