scholarly journals RENOPROTECTIVE EFFECT OF MELATONIN IN CONDITIONS OF ACUTE KIDNEY INJURY AND ALTERED PINEAL GLAND ACTIVITY

2019 ◽  
Vol 7 ◽  
pp. 812-816
Author(s):  
Tetiana Shchudrova ◽  
Yevheniia Dudka ◽  
Olena Korotun ◽  
Tetiana Bilous ◽  
Fedir Herman ◽  
...  

INTRODUCTION: Melatonin is a promising therapeutic agent due to its multiple beneficial effects, wide availability and relatively high safety. As melatonin acts as a chronobiotic agent, its adequate production by the pineal gland allows for adaptation to environmental changes, while disturbances in melatonin secretion are associated with health disorders. The renoprotective effect of exogenous melatonin was established on different experimental models of acute kidney injury (AKI), while the influence of the altered pineal gland activity on the efficacy of melatonin treatment has not been investigated.    OBJECTIVES: The aim of this research was to study the renoprotective potential of melatonin in conditions of aminoglycoside-induced AKI against the background of pineal hypo- and hyperfunction. METHODS: Nonlinear mature white rats (n=40) were randomly divided into 5 groups. Animals from the I (Control), and II (AKI) group were kept under the natural light regimen. Pineal hypofunction was simulated in rats from the III group by maintenance under conditions of constant light at 500 lux (24.00 light : 0.00 darkness) for 7 days. Pineal hyperfunction was simulated in rats from the IV group by maintenance under conditions of constant darkness (0.00 light : 24.00 darkness). Toxic AKI (II-IV groups) was induced by daily administration of gentamicin at a dose of 80 mg/kg for 6 days. Animals from the III-IV groups were injected daily with melatonin at a dose of 5 mg/kg. 24 h after the last injection biochemical and histological examination was performed. For the statistical analysis SPSS 17.0 software was used. RESULTS: Nephrotoxicity of gentamicin caused significant (p<0.05) functional changes and structural alterations to the rat kidneys. Treatment with melatonin in conditions of gentamicin-induced kidney injury significantly limited the degree of damage to renal tissue and prevented a critical reduction in kidney function, confirming a protective effect of melatonin. At the same time, significant (p<0.05) differences between the indices of the III and IV group allow us to state, that treatment with exogenous melatonin on the background of endogenous melatonin deficiency was less effective in comparison to the administration of melatonin in conditions of pineal hyperfunction. CONCLUSION: Melatonin ameliorates gentamicin-induced kidney injury by the limitation of histopathological changes in kidney tissue and the preservation of kidney function. Pre-existing deficiency of endogenous melatonin decreases the resistance of kidneys to the damaging action of the toxin and lessens the protective effect of the exogenous melatonin. Alternatively, in rats with increased pineal gland activity and melatonin production, co-treatment with exogenous melatonin more effectively protects the kidney from gentamicin-induced structural and functional changes and prevents the development of renal failure.

2019 ◽  
Vol 3 (1) ◽  
pp. 28-37
Author(s):  
Annisa Wimaulia Azlin ◽  
Rachmat Hidayat ◽  
Kemas Ya'kub Rahadiyanto

Acute kidney injury (AKI) is a sudden decrease of kidney function. The incidence of AKI is increasing every year. One of the causes of AKI is the lack of blood supply to the kidneys (prerenal). At the present time, there are not many studies that report unilateral ischemic-reperfusion (UIR) duration which can cause kidney damage especially glomerulus. The aim of this study is to determine the effect of UIR duration to glomerular microscopic appearance, GFR and cystatin C produced in Wistar white rats. This study was performed in vivo by using Post-test Only Control Group Design. Unilateral Ischemic-Reperfusion was administered on the rat’s left kidney and recovery was done according to specified time. After recovery time, rat’s blood was taken, the rat was euthanized, and its kidneys were taken and stained with Picrosirius Red coloring. The kidneys were observed by using OptiLED and the photos were analyzed with ImageJ software. Blood samples were tested by ELISA to measure the cystatin C levels and the levels were converted into Larrson formula to obtain Glomerular Filtration Rate. The level of cystatin C increased along with the longer duration of UIR and compared inversely proportional to GFR which decreased along with the rise of UIR duration. Cystatin C and GFR had a significant mean difference (p<0.05) with all groups, except for the duration of the UIR group <60 minutes. The percentage of collagen obtained fluctuated but the whole group which was carried out by UIR had a significantly different collagen amount (p <0.05) with the sham-operated group. The average glomerular picture showed the addition of collagen, Bowman's capsule thickening and vascular retraction. The longer duration of UIR will worsen the kidney function.   Keywords: Unilateral Ischemic-Reperfusion, Cystatin C. Glomerular Filtration Rate, Collagen Area Fraction, Glomerulus


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhiya Deng ◽  
Maomao Sun ◽  
Jie Wu ◽  
Haihong Fang ◽  
Shumin Cai ◽  
...  

AbstractOur previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.


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.


Author(s):  
Yon-Suk Kim ◽  
Si-Heung Sung ◽  
Yujiao Tang ◽  
Eun-Ju Choi ◽  
Young-Jin Choi ◽  
...  

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