Gentamicin-induced Acute Kidney Injury Research Articles

Edible Bird Nest Protects the Kidney From Gentamicin Induced Acute Tubular Necrosis.

Every year, there are about 13.3 million cases of acute kidney injury (AKI). Although AKI is a preventable and treatable disease, if left untreated, it has high risk of multiple organ failure and progression to end stage kidney disease. Acute tubular necrosis (ATN) has been recognised as one of the major causes of AKI. Till to date, there is no effective supplement or medication in treating or reversing AKI. Most of the treatment strategies involve preventative measure to minimise the occurrence of AKI or to reverse the cause of AKI. Hence one of the primary area of research interests is to explore the potential treatment for AKI. Edible bird nests (EBN) are edible food produce by the swiftlet’s saliva, which is rich in sialic acids. Sialic acids are monosaccharides that play a vital role in maintaining the integrity and proper function of the human organs, including kidneys. EBN also contains epidermal growth factor, which is widely believed to have rejuvenation and tissue repairing properties. We initiate this study to study the potential reno-protective effect of edible bird’s nests by studying the Wistar rat model of gentamicin-induced AKI. Besides renal profiles, renal histology was also semiquantitatively assessed. In our study, pre-treatment with EBN prevented and ameliorated the gentamicin-induced AKI. To a lesser extent, post-treatment with EBN also protected the kidney from the toxic effect of gentamicin. Our findings are highly indicative that EBN possesses reno-protective properties.

Evaluation of symmetric dimethylarginine and Doppler ultrasonography in the diagnosis of gentamicin-induced acute kidney injury in dogs.

Acute kidney injury is a common problem in dogs and is associated with significant morbidity and mortality. So, the present study aimed to evaluate symmetric dimethylarginine (SDMA) and Doppler ultrasonography including resistive index (RI) in the diagnosis of acute kidney injury in dogs. Ten healthy mongrel dogs were injected with gentamicin sulfate 10% at the dose of 30 mg/kg body weight daily for 10 days for induction of acute kidney injury. Clinical, biochemical, ultrasonographic, and Doppler ultrasonographic examinations and urinalysis were performed for all dogs on 0 day before induction, on the 5th day, and on the 10th day of induction. The results of the current study showed significant increase in plasma level of SDMA, serum urea, creatinine, phosphorus, and potassium and a significant decrease in serum sodium, calcium, and chloride on the 5th day and 10th day of induction, and there was an increase in renal cortical echogenicity of the right and left kidney compared to adjacent liver and spleen, respectively. RI value showed a significant increase on the 5th day and 10th day of induction. The present study showed that SDMA is a sensitive and promising biomarker for diagnosis of acute kidney injury in dogs compared to routine biomarkers; also, the RI of Doppler ultrasonography is useful for early identifying acute kidney injury when the only observable change is an increase in cortical echogenicity.

The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation.

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.

Role of Retama Raetam on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

The methanol extract of the seeds of Retama raetam was studied for its preventive and curative effects in gentamicin-induced acute renal failure in rats. Twenty-four rats were divided into four different groups. Group 1 was served as a control group, Group 2 and 3 were administered a daily dose of gentamicin (40 mg/kg body weight s.c) for 13 days. In case of group 3, rats were administered with the extract (30 mg/kg b. wt.) from the 14th day onwards for 10 days. While in group 4 rats were treated with an oral dose of the extract equivalent to 30 mg/kg b. wt. after 2 hoursof subcutaneous injection of gentamicin for 13 days. Serum urea and creatinine levels were measured. Moreover, histopathological as well as morphometrical investigations were performed. In the gentamicin model, the methanol extract of R. raetam (30 mg/kg b. wt.) reduced blood urea and serum creatinine effectively in the curative and the preventive treatment. Light microscopic examination of the renal tissues from gentamicin-treated rats revealed severe histopathological and morphometrical changes, whereas specimens obtained from extract-treated rats revealed only mild changes. These findings recommend that the methanol extract of the seeds of R. raetam counteract the deleterious effect of gentamicin on renal tubular function and structure

Renal Inflammation and Innate Immune Activation Underlie the Transition From Gentamicin-Induced Acute Kidney Injury to Renal Fibrosis.

Subjects recovering from acute kidney injury (AKI) are at risk of developing chronic kidney disease (CKD). The mechanisms underlying this transition are unclear and may involve sustained activation of renal innate immunity, with resulting renal inflammation and fibrosis. We investigated whether the NF-κB system and/or the NLRP3 inflammasome pathway remain activated after the resolution of AKI induced by gentamicin (GT) treatment, thus favoring the development of CKD. Male Munich-Wistar rats received daily subcutaneous injections of GT, 80 mg/kg, for 9 days. Control rats received vehicle only (NC). Rats were studied at 1, 30, and 180 days after GT treatment was ceased. On Day 1, glomerular ischemia (ISCH), tubular necrosis, albuminuria, creatinine retention, and tubular dysfunction were noted, in association with prominent renal infiltration by macrophages and myofibroblasts, along with increased renal abundance of TLR4, IL-6, and IL1β. Regression of functional and structural changes occurred on Day 30. However, the renal content of IL-1β was still elevated at this time, while the local renin-angiotensin system remained activated, and interstitial fibrosis became evident. On Day 180, recurring albuminuria and mild glomerulosclerosis were seen, along with ISCH and unabated interstitial fibrosis, whereas macrophage infiltration was still evident. GT-induced AKI activates innate immunity and promotes renal inflammation. Persistence of these abnormalities provides a plausible explanation for the transition of AKI to CKD observed in a growing number of patients.

Immortalized canine adipose-derived mesenchymal stem cells alleviate gentamicin-induced acute kidney injury by inhibiting endoplasmic reticulum stress in mice and dogs

Adipose-derived mesenchymal stem cells have been used to treat acute kidney injury (AKI). The role of endoplasmic reticulum (ER) stress in AKI treatment with canine adipose-derived mesenchymal stem cells (cADSCs) remains unknown. This study intended to investigate the therapeutic effects of cADSCs cultured in different media on AKI in mice and dogs and reveal the role of ER stress in this process. The mice were divided into two branches: a control group and a gentamicin induced group (this group treated with low-serum ADSC or high-serum ADSC or 4-phenylbutyric acid (4-PBA)). The dogs were divided into control, model, and cell-injected groups. To suppress ER stress, mice were simultaneously treated with 4-PBA. The results showed there were improvements in renal function and tissue damage and a corresponding decrease in ER stress in the kidneys of the mice that received cell injection. However, the cells cultured with 2% FBS showed a better growth state and resulted in lower ER stress levels in treated kidneys. In the 4-PBA-treated group, ER stress was suppressed, and there was corresponding kidney injury recovery. Similarly, both kidney damage and ER stress were alleviated after AKI dogs were injected with the cells. Our findings reveal that both allogeneic and xenogeneic cADSCs were effective treatments for AKI by inhibiting ER stress. These results also provide evidence for a new clinical therapy for acute renal disease in pets.

Glutamine alleviates the renal dysfunction associated with gentamicin-induced acute kidney injury in Sprague-Dawley rats.

Sepsis is a clinical condition caused by an uncontrolled response to an infection, leading to acute kidney injury (AKI) and an increased risk of mortality. Although life support and antibiotic therapy are available, the mortality rate remains high in patients with sepsis. The present study investigated the therapeutic effect of glutamine on gentamicin-induced acute kidney injury in Sprague-Dawley rats. We randomly grouped 24 male rats to the normal control, AKI (control), glutamine 50 mg/kg, and glutamine 500 mg/kg groups. The dose was administered orally for 14 consecutive days. Rats treated with glutamine 500 mg/kg showed changes in systolic blood pressure. Glutamine increased renal blood flow, creatinine clearance, and the levels of potassium, creatinine, blood urea nitrogen, and urine osmolality, while reducing the relative excretion of sodium, potassium, urinary sodium, and plasma blood urea nitrogen and creatinine levels. In our study, glutamine supplementation reduced gentamicin-induced oxidative stress and increased catalase, superoxide dismutase, glutathione peroxidase, and glutathione levels in AKI rats. In addition, glutamine supplementation attenuated the severity of pathological features in this model. Collectively, our results showed that gentamicin has therapeutic potential against gentamicin-induced AKI due to its ability to mitigate the effects of oxidative stress.

The Effect of Tarantula cubensis Extract on Gentamicin-Induced Acute Kidney Injury in Ovariectomized Rats

The Effect of Tarantula cubensis Extract on Gentamicin-Induced Acute Kidney Injury in Ovariectomized Rats

Urinary microRNAs miR-15b and miR-30a as novel noninvasive biomarkers for gentamicin-induced acute kidney injury

MicroRNAs serve as potential biomarkers in various pathological models, and are stable and detectable in biofluids. We investigated the urinary microRNA expression profile in a gentamicin-induced acute kidney injury canine model using RNA sequencing. A total of 234 differentially expressed microRNAs were screened after 12 consecutive days of gentamicin administration (P < 0.05). Six candidate microRNAs (miR-15b, -15b-3p, -16, -30a, -30a-3p, and -30c-2-3p) were selected according to a set criterion, and validated by real-time quantitative PCR. The diagnostic values of these six candidate microRNAs were better than the traditional serum biomarkers (all P < 0.05). Further, using receiver operating characteristic curve analysis, we found that miR-15b and -15b-3p were superior to urinary kidney injury molecule-1 (both P < 0.05). Moreover, miR-15b and -30a levels in the urine samples significantly correlated with their respective levels in the kidney tissue samples (r=0.512 and 0.505, respectively, both P < 0.05). Our data concluded that miR-15b and -30a may be promising biomarkers for renal toxicity.

Protective Effect of Procambarus Clarkia Hemolymph against Acute Kidney Injury Induced by Gentamicin in Rats

Background: P.clarkii hemolymph has several pharmacological activities against inflammation, bacteria and tumor. The current study aimed to explore the efficacy of P.clarkii hemolymph against the renal toxicity induced by Gentamicin (GM) in rats. Methods: The animals were divided randomly into three groups (six per group): control, GM and P.clarkii. Tissues toxicity was established after injection of GM daily for eight days at a dose 100 mg/kg. Kidney functions, liver functions, oxidative stress markers and histopathology of tissues were investigated in the study. Results: P.clarkii treated rats showed a significant decrease in urea, creatinine, uric acid, ALT, AST, and MDA levels while GSH and CAT levels increased. The histology of kidney investigation showed partial restoration of renal architecture. Conclusion: The study results revealed the protective role of p.clarkii hemolymph against gentamicin-induced acute kidney injury in rats.

Pirfenidone attenuates gentamicin-induced acute kidney injury by inhibiting inflammasome-dependent NLRP3 pathway in rats

Acute kidney injury (AKI) is an abrupt and usually reversible decline in renal function. AKI is considered one of the main drawbacks of the use of gentamicin that critically limits its clinical use. In this study, pirfenidone, an oral antifibrotic drug, was given to rats (200 mg/kg, p.o., daily) for seven days alone before the initiation of gentamicin treatment and continued for seven days alongside daily gentamicin injections. In gentamicin group, gentamicin was given to Wistar rats (100 mg/kg, i.p., daily) for seven days to induce AKI. Pirfenidone managed to alleviate gentamicin-induced AKI by improving kidney function parameters including serum creatinine, blood urea nitrogen (BUN), proteinuria, relative kidney-to-body weight ratio and creatinine clearance. Pirfenidone decreased cytotoxicity induced by gentamicin by decreasing lactate dehydrogenase (LDH) activity and improving histologic picture of tubules and glomeruli. Pirfenidone also alleviated oxidative stress induced by gentamicin by reducing malondialdehyde (MDA) and elevating reduced glutathione (GSH). Pirfenidone prevented the upregulated inflammasome pathway markers in the kidney. It succeeded in decreasing toll like recpetor-4 (TLR4), nuclear factor-kappa B (NF-κB), nucleotide-binding oligomerization domain [NOD]-like pyrin domain containing protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β) and IL-18 levels. Additionally, Pirfenidone caused a decrease in macrophage infiltration displayed by reduction in renal monocyte chemoattractant protein-1 (MCP-1) levels. To sum up, pirfenidone can effectively mitigate gentamicin-induced AKI by inhibiting oxidative stress, macrophage infiltration and inflammasome-dependent NLRP3 pathway-induced inflammation.

Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency.

Gentamicin is a used antibiotic that causes nephrotoxicity in 10–20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo. Porcine renal cells and rats were treated with gentamicin and/or cilastatin. In vivo nephrotoxicity was analyzed by measuring biochemical markers and renal morphology. Different apoptotic, oxidative and inflammatory parameters were studied at cellular and systemic levels. Megalin, mainly responsible for the entry of gentamicin into the cells, was also analyzed. Results show that cilastatin protects cells from gentamicin-induced AKI. Cilastatin decreased creatinine, BUN, kidney injury molecule-1 (KIM-1) and severe morphological changes previously increased by gentamicin in rats. The interference of cilastatin with lipid rafts cycling leads to decreased expression of megalin, and therefore gentamicin uptake and myeloid bodies, resulting in a decrease of apoptotic, oxidative and inflammatory events. Moreover, cilastatin did not prevent bacterial death by gentamicin. Cilastatin reduced gentamicin-induced AKI by preventing key steps in the amplification of the damage, which is associated to the disruption of megalin-gentamicin endocytosis. Therefore, cilastatin might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced AKI in the clinical setting.

Gentamicin-Induced Acute Kidney Injury in an Animal Model Involves Programmed Necrosis of the Collecting Duct.

Gentamicin is a potent aminoglycoside antibiotic that targets gram-negative bacteria, but nephrotoxicity limits its clinical application. The cause of gentamicin-induced AKI has been attributed mainly to apoptosis of the proximal tubule cells. However, blocking apoptosis only partially attenuates gentamicin-induced AKI in animals. Mice treated with gentamicin for 7 days developed AKI, and programmed cell death pathways were examined using pharmacologic inhibitors and in RIPK3-deficient mice. Effects in porcine and murine kidney cell lines were also examined. Gentamicin caused a low level of apoptosis in the proximal tubules and significant ultrastructural alterations consistent with necroptosis, occurring predominantly in the collecting ducts (CDs), including cell and organelle swelling and rupture of the cell membrane. Upregulation of the key necroptotic signaling molecules, mixed lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting serine/threonine-protein kinase 3 (RIPK3), was detected in gentamicin-treated mice and in cultured renal tubule cells. In addition, gentamicin induced apical accumulation of total and phosphorylated MLKL (pMLKL) in CDs in mouse kidney. Inhibiting a necroptotic protein, RIPK1, with necrostatin-1 (Nec-1), attenuated gentamicin-induced necrosis and upregulation of MLKL and RIPK3 in mice and cultured cells. Nec-1 also alleviated kidney inflammation and fibrosis, and significantly improved gentamicin-induced renal dysfunction in mice. Furthermore, deletion of RIPK3 in the Ripk3-/- mice significantly attenuated gentamicin-induced AKI. A previously unrecognized role of programmed necrosis in collecting ducts in gentamicin-induced kidney injury presents a potential new therapeutic strategy to alleviate gentamicin-induced AKI through inhibiting necroptosis.

Protective effect of Polygonatum sibiricum polysaccharides on gentamicin-induced acute kidney injury in rats via inhibiting p38 MAPK/ATF2 pathway

The aim of this study was to investigate the protective effect of Polygonatum sibiricum polysaccharides (PSP) on acute kidney injury (AKI) in rats. The AKI model was established with 100 mg/kg of gentamicin (GM) intramuscularly. Six hours post-injection, rats were given intragastrically different dosages of PSP (0.25, 0.5, and 1 g/kg) for seven consecutive days. Results showed that compared with the model group, the kidney coefficient of rats decreased significantly (P < 0.05), and rat serum CRE and urea levels were significantly decreased (P < 0.05) in the PSP treatment group. The expression of NGAL, KIM-1, IL-1β, IL-6, TNF-α, and p38 MAPK mRNA in the kidney were significantly decreased (P < 0.05). The protein expression of p38 MAPK, p-p38 MAPK, and p-ATF2 were decreased to different degrees. Among the three-PSP treatment groups, the medium-dose group displayed the most protective effects. In conclusion, PSP had a powerful protective effect on GM-induced AKI in rats, it decreased the expression of NGAL or KIM-1 mRNA in kidney tissue and inhibited the p38 MAPK/ATF2 signaling pathway and the production of inflammatory factors TNF-α, IL-1β, and IL-6.

The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats

AimInvestigating the impact of 17β-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. Main methodsThree weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty–eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule −1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. Key findingsEstrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SignificanceEstrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.

Screening of Early Diagnostic Markers of Gentamicin-induced Acute Kidney Injury in Canines.

IntroductionThe value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs.Material and MethodsSubcutaneous gentamicin injection in 16 healthy adult beagles made the AKI model. Blood was sampled every 6 h to detect NGAL, Kim-1, L-FABP, and serum creatinine (SCr) concentrations. Kidney tissue of two dogs was taken before the injection, as soon as SCr was elevated (78 μmol/L), and when it had risen to 1.5 times the baseline, and haematoxylin-eosin staining and transmission electron microscopy (TEM) were used to observe changes.ResultsNGAL, Kim-1, and SCr levels were significantly increased (P < 0.05) at 18, 30, and 78 h post injection, but L-FABP concentration was not associated with renal injury. At the earliest SCr elevation stage, findings were mild oedema, degeneration, and vacuolisation in renal tubular epithelial cells in pathology, and mild cytoplasmic and mitochondrial oedema in TEM. At this time point, NGAL and Kim-1 concentrations were significantly increased (P < 0.05), indicating that these two molecules biomark early kidney injury in dogs. Using receiver operating characteristic curve analysis, their warning levels were > 25.31 ng/mL and > 48.52 pg/mL.ConclusionPlasma NGAL and Kim-1 above warning levels are early indicators of gentamicin-induced AKI in dogs.

First person – Lauren Brilli Skvarca and Hwa Han

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Lauren Brilli Skvarca and Hwa Han are co-first authors on ‘Enhancing regeneration after acute kidney injury by promoting cellular dedifferentiation in zebrafish’, published in DMM. Lauren is a Pathologist Investigator Residency Research Training (PIRRT) Fellow at the University Pittsburgh Medical Center (UPMC), USA, in the lab of Carl Hubel, investigating maternal-fetal cell interactions contributing to placental vascular changes in preeclampsia and postpartum maternal cardiovascular risk. Hwa is a PhD graduate student in the lab of Neil Hukriede at the University of Pittsburgh School of Medicine, USA, and is involved in characterizing regenerative cellular mechanisms in gentamicin-induced acute kidney injury using larval zebrafish as a model organism.

Therapeutic effects of human stem cells in experimentally induced acute kidney injury in rats

Objective The aim of this study was to evaluate the effect of stem cell therapy in drug-induced acute kidney injury in rats. Background Acute kidney injury (AKI) is defined as a rapid decrease in renal functions within few days; thus drug-induced AKI is a frequent entity in clinical medicine. Stem cell therapy provides a hopeful prospective for injured tissues and for repairing damaged organs. Materials and methods A total of 30 male Swiss albino rats were used in the present study. The animals were randomly divided into three groups. Group I: control group (10 rats). Group II: AKI group (10 rats), gentamicin-induced AKI rat models were used. Group III: stem-cell-treated AKI group (10 rats). Rats with established AKI were injected with CD34-positive stem cells. The three studied groups were assessed for serum urea, blood urea nitrogen, serum creatinine, and kidney injury molecule 1 (KIM-1). At the end, all the rats were killed and their kidneys were excised for histopathology and immunohistochemical studies. Results Serum KIM-1 level was significantly higher in the AKI group in comparison with both control group and stem-cell-treated group (P = 0.001), whereas no statistically significant difference was found between control group and stem-cell-treated group regarding serum KIM-1 level (P = 0.755). The results of the immunohistopathological studies have shown no significant changes between control group and AKI-stem-cell-treated group. Conclusion This study showed that AKI markers improved after treatment by stem cells in AKI-induced group.

MORPHOFUNCTIONAL CHANGES IN KIDNEYS OF RATS WITH GENTAMICIN-INDUCED ACUTE KIDNEY INJURY AND USE OF MELATONIN

Aminoglycosides are effective antibiotics, but their accumulation in kidney cortex causes nephrotoxic effects in 20-30% of patients, which significantly limits their use. For this reason, search for the new therapies aimed at prevention of gentamicin-induced acute kidney injury (AKI) is highly relevant. Thus, the objective of our research was to study the functional and histopathological changes in kidneys of rats with gentamicin-induced AKI, and estimate the renoprotective potential of pineal hormone melatonin, which possesses antioxidant, anti-inflammatory and immunomodulatory effects. The study was conducted on 24 non-linear male rats. Gentamicin-induced AKI was modeled by daily administration of 4% gentamicin sulphate (80 mg/kg) for 6 days. Melatonin (Sigma Aldrich, USA) was injected daily at a dose of 5 mg/kg. Functional state of kidneys was assessed by diuresis, creatinine clearance, urine protein excretion, fractional excretion of sodium, and plasma potassium level. Documentation of the pathological processes was performed by the computer morphometry of objects in histological preparations. Statistical analysis of the data was performed using SPSS 17.0 software. Administration of gentamicin resulted in a significant impairment of renal function of experimental animals. A decrease in creatinine clearance by 3.1 times along with a reduction of diuresis by 1.9 times, and an increase in plasma creatinine concentration by 2.6 times was observed. There also was an increase in urine protein level by 5.2 times, an elevation of fractional sodium excretion and a reduction of plasma potassium level. Use of melatonin caused a significant improvement of renal function comparing to model pathology group. Functional disturbances were accompanied with the significant histopathological changes in kidney tissue: necrosis of the 27±5.2% epithelial cells of proximal tubules with the signs of hydropic vacuolization (7±2.1%) or reversible hydropic swelling (76±1.5%) in the rest of cells; swelling or deformation of some glomeruli. In the medulla tubular lumen were dilated and partially filled with hyaline casts, tubular cells had signs of dystrophy. Use of melatonin contributed to the restraint of the histopathological changes, confirmed by the decrease of the prevalence and severity of tubular necrosis (1.2%), dystrophy (64±2.3%), and injury of glomeruli. Obtained results verify the significant nephroprotective effect of pineal hormone melatonin, providing a background for the further in-depth study of its renal effects as well as its prospects as a nephroprotector.

Surgical prophylaxis with gentamicin and acute kidney injury: a systematic review and meta-analysis.

Gentamicin has been increasingly used instead of cephalosporins for surgical prophylaxis in an attempt to reduce the rate of "Clostridium difficile" infection. There are limited data regarding nephrotoxicity related to gentamicin in these patients. We have conducted a systematic review and meta-analysis to evaluate the risk of acute kidney injury (AKI) in gentamicin-containing surgical prophylactic regimens, compared to regimens without gentamicin, in several types of surgery. Electronic searches were performed using PubMed and Embase, including terms for "AKI, gentamicin, and surgical prophylaxis" with and without MeSH/EMTREE functions. Statistical analysis was then performed using a random-effect model; risk ratios (RR), risk differences (RD) and heterogeneity (I2) were calculated. Funnel plot was used for assessment of publication bias. Eleven studies with fifteen cohorts with 18,354 patients were included in the analysis. Subgroup analysis was performed according to surgery type. We have found that antibiotic prophylaxis with gentamicin containing regimen has significant risk for developing postoperative AKI in orthopedic surgery (RR 2.99; 95% CI: 1.84, 4.88). The results were inconclusive in other types of surgery. Funnel plot indicates potential publication bias. Gentamicin-induced AKI is significant in patients undergoing orthopedic surgery. Physicians should consider risks and benefits of using this regimen in individual patients.