Sudden Loss Of Renal Function Research Articles

Acteoside and isoacteoside alleviate renal dysfunction and inflammation in lipopolysaccharide-induced acute kidney injuries through inhibition of NF-κB signaling pathway.

Acute kidney injury (AKI) is a sudden loss of renal function with a high mortality rate and inflammation is thought to be the underlying cause. The phenylpropanoid components acteoside (ACT) and isoacteoside (ISO), which were isolated from Cistanche deserticola Y.C.Ma, have been reported to have preventive effects against kidney disorders. This study aimed to investigate the anti-inflammatory properties and protective mechanisms of ACT and ISO. In this investigation, kidney function was assessed using a semi-automatic biochemical analyzer, histopathology was examined using Hematoxylin-Eosin staining and immunohistochemistry, and the concentration of inflammatory cytokines was assessed using an enzyme-linked immunosorbent assay (ELISA) test. In addition, using Western blot and q-PCR, the expression of proteins and genes connected to the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced AKI was found. The findings showed that under AKI intervention in LPS group, ACT group and ISO group, the expression of Rela (Rela gene is responsible for the expression of NFκB p65 protein) and Tlr4 mRNA was considerably elevated (P<0.01), which led to a significant improvement in the expression of MyD88, TLR4, Iκ-Bɑ and NF-κB p65 protein (P<0.001). The levels of Alb, Crea and BUN (P<0.001) increased along with the release of downstream inflammatory factors such as IL-1β, IL-6, Cys-C, SOD1 and TNF-α (P<0.001). More importantly, the study showed that ISO had a more favorable impact on LPS-induced AKI mice than ACT. In conclusion, by inhibiting NF-κB signaling pathway, ACT and ISO could relieve renal failure and inflammation in AKI, offering a fresh possibility for the therapeutic management of the condition.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 μM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Fulvestrant alleviates cisplatin-induced acute kidney injury via repression of BNIP3-mediated apoptosis and autophagy.

Cisplatin-induced acute kidney injury (AKI) is a clinical disease characterized by a sudden loss of renal function within a few hours or days, due to cisplatin uptake. Fulvestrant is an oestrogen receptor alpha (ERα) antagonist used for endocrine therapy. However, the role of fulvestrant in cisplatin-induced AKI remains unclear. In this study, we investigated the effects of fulvestrant on the regulation of apoptotic cell death and autophagic response in cisplatin-induced AKI. The human kidney proximal tubule epithelial cell line (HK-2) was co-treated with fulvestrant and cisplatin. C57BL/6 mice were subcutaneously injected with fulvestrant and cisplatin was administered via intraperitoneal injection. First, cisplatin treatment increased ERα expression, apoptosis, and autophagy in HK-2 cells. Fulvestrant treatment decreased apoptosis and autophagy, which were accompanied by cisplatin treatment in HK-2 cells. Consistent with in vitro results, cisplatin treatment significantly increased ERα expression in vivo. Additionally, cisplatin treatment increased renal injury, apoptosis, and autophagy. Surprisingly, compared to that in the cisplatin-treated mice group, reduced cisplatin-induced renal injury, apoptosis, and autophagy was observed in the cisplatin+fulvestrant-treated mice group. In summary, these results suggest that fulvestrant plays an important role in cisplatin-induced AKI by decreasing apoptosis and autophagy.

Effects of Albizia julibrissin Durazz through Suppression of Mitochondrial Fission and Apoptosis in Cisplatin-induced Acute Kidney Injury

Albizia julibrissin Durazz. (AJ; family Minosaceae) is widely distributed worldwide, and its stem bark has been used as a traditional herbal medicine. Acute kidney injury (AKI) is a clinical syndrome that results in sudden loss of renal function. This study aimed to investigate the effects of AJ against cisplatin-induced AKI using a human kidney proximal tubule epithelial cell line (HK-2) and cisplatin-treated mice. In vitro, cisplatin treatment increased apoptosis in HK-2 cells. However, AJ treatment decreased apoptosis of cisplatin-treated HK-2 cells. In vivo, cisplatin treatment accelerated renal injury by increasing the levels of renal injury markers, such as blood urea nitrogen, creatinine, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin, which were reversed by AJ treatment. Histopathologically, AJ treatment resulted in decreased renal damage with less tubular necrosis and brush border desquamation compared with the AKI group. Additionally, cisplatin treatment upregulated mitochondrial fission, a pathological characteristic of AKI, which was downregulated by AJ treatment. Along with increased mitochondrial fission, AJ treatment also reduced cisplatin-induced apoptosis. These results suggest that AJ may be a potential therapeutic agent for cisplatin-induced AKI.

Preferential siRNA delivery to injured kidneys for combination treatment of acute kidney injury

Acute kidney injury (AKI) is characterized by a sudden loss of renal function and is associated with high morbidity and mortality. Tumor suppressor p53 and chemokine receptor CXCR4 were both implicated in the AKI pathology. Here, we report on the development and evaluation of polymeric CXCR4 antagonist (PCX) siRNA carrier for selective delivery to injured kidneys in AKI. Our results show that PCX/siRNA nanoparticles (polyplexes) provide protection against cisplatin injury to tubule cells in vitro when both CXCR4 and p53 are inhibited. The polyplexes selectively accumulate and are retained in the injured kidneys in cisplatin and bilateral ischemia reperfusion injury models of AKI. Treating AKI with the combined CXCR4 inhibition and p53 gene silencing with the PCX/sip53 polyplexes improves kidney function and decreases renal damage. Overall, our results suggest that the PCX/sip53 polyplexes have a significant potential to enhance renal accumulation in AKI and deliver therapeutic siRNA.

INCIDENCE, RISK FACTORS AND OUTCOMES OF ACUTE KIDNEY INJURY IN PRETERM NEWBORNS

Acute kidney injury is a sudden loss of renal function that results in deterioration of the &nbsp;renal’s ability to excrete urine in sufficient quantity and adequate composition. The aim of the study was to determine the incidence, risk factors and outcomes of acute kidney injury in preterm newborns. The study was conducted at the University Clinic of Pediatrics–Skopje. It was a clinical, epidemiological prospective study. In the period of two years, 40 preterm newborns hospitalized at the Intensive Care Unit (ICU) with documented kidney injury were analyzed. Medical data records of hospitalized preterm infants with kidney injury were processed. The material was statistically analyzed using methods of descriptive statistics. We evaluated 40 preterm newborns with documented acute kidney injury, who at the period of 2 years were treated in the ICU. The prevalence of kidney injury was 6.9%. Most of the involved preterm newborns were male (72%), and born at 32 to 37 weeks with low birth weight (58%). Prerenal injury was evaluated in 79.5% of the cases. The mortality rate was 36% and it was significantly higher in the group of preterm infants born under 28 weeks, with Extremely Low Birth Weight Newborns ELBW. (P=0.01). Acute kidney injury is a life threatening condition with a still high mortality rate. Appropriate treatment of kidney injury in newborns with ELBW improves the outcomes and reduces the mortality of the disease. Key words: acute kidney injury, preterm newborns, ELBW

Glycogen synthase kinase-3β inhibits tubular regeneration in acute kidney injury by a FoxM1-dependent mechanism.

Acute kidney injury (AKI) is characterized by injury to the tubular epithelium that leads to the sudden loss of renal function. Proper tubular regeneration is essential to prevent progression to chronic kidney disease. In this study, we examined the role of FoxM1, a forkhead box family member transcription factor in tubular repair after AKI. Renal FoxM1 expression increased after renal ischemia/reperfusion (I/R)-induced AKI in mouse kidneys. Treatment with thiostrepton, a FoxM1 inhibitor, reduced FoxM1 regulated pro-proliferative factors and cell proliferation in vitro, and tubular regeneration in mouse kidneys after AKI. Glycogen synthase kinase-3 (GSK3) was found to be an upstream regulator of FoxM1 because GSK3 inhibition or renal tubular GSK3β gene deletion significantly increased FoxM1 expression, and improved tubular repair and renal function. GSK3 inactivation increased β-catenin, Cyclin D1, and c-Myc, and reduced cell cycle inhibitors p21 and p27. Importantly, thiostrepton treatment abolished the improved tubular repair in GSK3β knockout mice following AKI. These results demonstrate that FoxM1 is important for renal tubular regeneration following AKI and that GSK3β suppresses tubular repair by inhibiting FoxM1.

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice.

Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

Abstract P144: Integrin β1 in Tubular Epithelium Protects From Acute Injury Induced Fibrosis

Acute kidney injury (AKI) results in the sudden loss of renal function primarily due to renal tubular injury. Repeated injury or maladaptive recovery lead to chronic kidney diseases. All forms of chronic kidney disease are characterized by excessive extracellular matrix (ECM) accumulation. The proximal tubule cells that are injured but not detached from the basement membrane are critical for the restoration of renal functions after the injury incidence. Renal tubular epithelial cell adhesion, migration, and proliferation are required for the kidney to recover from sub-lethal injury. These processes require the ability of cells to interact with the ECM. Integrin, which exists as a complex of α and β subunits, are the principal receptors for ECM proteins. Integrin β1 is the major integrin subunit present in kidney and critically regulates renal epithelial cell functions. We investigated the importance of Integrin β1 in kidney proximal tubule epithelial cells. Integrin β1 was deleted from these cells using the γ-gt cre. These KO mice had no morphological abnormalities but have a higher urine osmolality (2369±881 mΩ) compared to WT (2098±945 mΩ). By using a nephrotoxic injury model, we investigated the role of integrin β1 in AKI. Samples were collected on 3, 5, 7 and 14 days after injury to assess the nature of injury and recovery. Integrin β1 KO mice were more susceptible to injury as evident by protein casts and tubule dilation of tubules. The blood urea nitrogen (BUN) from the plasma showed increased BUN level in KO animals compared to WT controls (26.78±8.23 and 34.05±7.11). After the injury the level was increased to 52.26±18.37 in WT and 60.34±11.58 KO suggesting both were injured to a similar extent. After 14 days the WT recovered better than KO animals (BUN 37.33±10.12 and 48.73±15.92). After 14 KO mice had more collagen deposition compared to WT animals. This data suggests the importance of integrin β1 in the tubular epithelium in promoting the recovery from injury and preventing its progression to chronic kidney disease.

Preconditioning by aerobic exercise reduces acute ischemic renal injury in rats.

Acute kidney injury (AKI) can be defined as the sudden loss of renal function associated with structural changes in the kidneys. Currently, 13.3 million people die of AKI around the world. Normally aerobic exercise is used both as/for the treatment and prevention of high blood pressure, metabolic disease and Diabetes mellitus (DM). Nevertheless, exercise preconditioning must be a crucial resource in the prevention and mitigation of AKI. The aim of this study was to evaluate the effects of the exercise preconditioning on renal IR (ischemic/reperfusion) experimental model. Male Wistars rats were divided into three groups (n = 9): sham (S), ischemic/reperfusion (IR), exercise + ischemic/reperfusion (EX + IR). IR renal injury was induced by clamping the bilateral renal artery for 45 min. The rats were subjected to exercise 5 days a week for 4 weeks with progressive intensity and duration. The group treated with exercise preconditioning, showed additional improvements in various parameters, including serum creatinine, proteinuria, and decrease of the severity of the tubular injury and activated caspase‐3 levels (P < 0.05). The previous aerobic exercise‐induced renoprotection in the IR injury. We anticipate that the practice of physical exercise in healthy individuals can also be useful for the prevention and attenuation of AKI.

The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury

Background: Acute kidney injury (AKI) refers to a sudden loss of renal function. This study was performed to identify the key RNAs acting in the mechanism of sepsis-induced AKI.Methods: Microarray dataset GSE94717 (including six sepsis-induced AKI samples and three control samples) was downloaded from Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were identified. The miRNA targets were predicted and enrichment analysis was performed. Protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) regulatory networks were constructed. Mouse podocytes were treated with lipopolysaccharide (LPS), following by cell viability and PCR analysis. Cellular apoptosis and the ceRNA network were validated.Results: Thirty-one common DE-miRNAs (two up-regulated and 29 down-regulated) by AKI versus control and male AKI versus control were identified. We found the targets of miR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway, and those of miR-29b-3p and miR-16-5p were enriched in PI3K-Akt signaling pathway. RNAs including miR-15b-5p, miR-15a-5p, miR-107, XIST, miR-16-5p, and cullin 3 gene (CUL3) were included in the ceRNA regulatory network. The downregulation of miR-15a-5p and miR-15b-5p and the upregulation of lncRNA XIST and CUL3 gene were validated using qPCR. The miR-15a-5p-XIST-CUL3 regulatory axis was identified and was validated. We confirmed that LPS inhibited the growth of mouse podocytes and seven of the ten miRNAs, but upregulated XIST and CUL3. Transfection analysis showed XIST siRNA enhanced LPS-induced MPC5 cell apoptosis and miR-15a-5p inhibitor reserved it, so did as CUL3 overexpression for miR-15a-5p mimics.Conclusion: The miR-15a-5p-XIST-CUL3 regulatory axis was related to the pathogenesis of sepsis-induced AKI.HighlightsTotally, 31 miRNAs were dysregulated between disease and control groups.MiR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway.MiR-16-5p and miR-29b-3p were implicated in PI3K-Akt signaling pathway.The miR-15a-5p-XIST-CUL3 axis was critical for sepsis-induced AKI.

CLINICAL FACTORS AND ANTICOAGULATION LEVEL THAT DETERMINE THE SUDDEN LOSS OF KIDNEY FUNCTION IN PATIENTS LONG-TAKING WARFARIN (A 5-YEAR PROSPECTIVE, OBSERVATIONAL STUDY)

Assessment of kidney function is mandatory in all cardiac patients, and patients with atrial fibrillation represent a category of patients with high thrombotic risk, which increases the risk of decreased kidney function during follow-up. Controversial issues of warfarin-associated nephropathy are important today. A prospective 5-year follow-up of 172 patients receiving warfarin therapy showed that 26.7% had the sudden loss of renal function (SLRF) (defined as an annual decline in glomerular filtration rate (GFR) ≥ 3 ml/min/1.73 cm2). Based on the results of the ROC analysis, it was determined that the maximum INR > 3.97 was associated with the SLRF (the area under the curve was 0.649, the sensitivity 56.5%, the specificity 74.6%, p = 0.003), and the maximum INR> 6.0 increased the specificity of the analysis to 96%. The study showed that for patients who had a maximum INR value ≥ 3.97, the mean delta of changes in GFR was negative, and the largest negative dynamics was characteristic for patients with a maximum INR ≥ 6.0. The estimated odd ratio of SLRF confirms the high prognostic significance of the maximum INR value. The maximum INR 3.97-5.9 increased the risk of SLRF by 3.07 times (95% CI 1.5241-6.2017, p = 0.0017), as well as the INR ≥ 6.0 (OR 3.05, 95% CI 1.0073-9.2433, p = 0.0485). The multifactorial discriminant analysis showed that the SLRF predictors against the background of 5-year warfarin therapy included the maximum INR ≥ 3.97 (F = 10.45, p = 0.0014), IHD (F = 8.7, p = 0.0036), diabetic nephropathy (F = 5.29, p = 0.0226) and the CHA2DS2-VASc score ≥ 4 (F = 5.05, p = 0.0258).

Intermittent hemodialysis for patients with acute kidney injury (AKI): Outcome in a tertiary level hospital

&lt;p&gt;&lt;strong&gt;INTRODUCTION:&lt;/strong&gt; Acute kidney injury (AKI) is the sudden loss of renal function with accumulation of nitrogenous waste compounds. In developing countries, community acquired AKI is common than AKI in hospitalized septic patients. With conservative management many patients recover renal function however few require renal support with intermittent Hemodialysis (HD). We conducted a study to find out the etiology and outcome of the patients presenting with AKI who required dialysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;METHODS: &lt;/strong&gt;This is a descriptive follow up study of the patients who needed renal replacement therapy in the form of HD presenting to our Nephrology unit of the hospital over a period of two years. Patients were followed up for three months post discharge. Data were tabulated and analyzed using SPSS software.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;RESULTS: &lt;/strong&gt;Total 50 patients were included in study with 67% male. The commonest etiologies were urinary tract infection (30%) and acute gastroenteritis (24%).The mean creatinine at the time of nephrology consultation, maximum level and at the time of discharge were 6.5(SD± 2.62), 7.3(SD ±2.13) and 2.2(SD ±1.75) respectively. Uremia with anuria was the most common reason for the initiation of HD in 54% cases. The mean number of intermittent HD used was 3.36. Complete recovery was seen in 68%, death in 26% and CKD in 6%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;CONCLUSION: &lt;/strong&gt;UTI followed by acute gastroenteritis are the leading cause of AKI in our tertiary level hospital. Timely initiated renal replacement therapy in the form of intermittent HD could lead to substantial renal recovery in almost three fourth of patients.&lt;/p&gt;

Intermittent Hemodialysis For Patients With Acute Kidney Injury (AKI): Outcome In A Tertiary Level Hospital

INTRODUCTION: Acute kidney injury (AKI) is the sudden loss of renal function with accumulation of nitrogenous waste compounds. In developing countries, community acquired AKI is common than AKI in hospitalized septic patients. With conservative management many patients recover renal function however few require renal support with intermittent Hemodialysis (HD). We conducted a study to find out the etiology and outcome of the patients presenting with AKI who required dialysis.METHODS: This is a descriptive follow up study of the patients who needed renal replacement therapy in the form of HD presenting to our Nephrology unit of the hospital over a period of two years. Patients were followed up for three months post discharge. Data were tabulated and analyzed using SPSS software.RESULTS: Total 50 patients were included in study with 67% male. The commonest etiologies were urinary tract infection (30%) and acute gastroenteritis (24%).The mean creatinine at the time of nephrology consultation, maximum level and at the time of discharge were 6.5(SD± 2.62), 7.3(SD ±2.13) and 2.2(SD ±1.75) respectively. Uremia with anuria was the most common reason for the initiation of HD in 54% cases. The mean number of intermittent HD used was 3.36. Complete recovery was seen in 68%, death in 26% and CKD in 6%.CONCLUSION: UTI followed by acute gastroenteritis are the leading cause of AKI in our tertiary level hospital. Timely initiated renal replacement therapy in the form of intermittent HD could lead to substantial renal recovery in almost three fourth of patients.

Expression and Function of Interleukin-1β-Induced Neutrophil Gelatinase-Associated Lipocalin in Renal Tubular Cells.

Acute kidney injury (AKI) is characterized by a sudden loss of renal function. Early recognition of AKI, especially in critically ill patients, is essential for adequate therapy. Currently, neutrophil gelatinase-associated lipocalin (NGAL) is considered to be an effective biomarker of AKI; however, the regulation of its expression and function in renal tubular cells remains unclear. In this study, we investigated the regulation of the expression and function of NGAL in IL-1β-treated Madin–Darby canine kidney (MDCK) cells as a model of renal tubular cells. IL-1β induced a disturbance in the localization of E-cadherin and zonaoccludin-1 (ZO-1). The transepithelial electrical resistance (TER) also decreased 5 days after IL-1β treatment. IL-1β induced NGAL mRNA expression and protein secretion in a time- and dose-dependent manner, which occurred faster than the decrease in TER. In the presence of ERK1/2 and p38 inhibitors, IL-1β-induced NGAL mRNA expression and protein secretion were significantly attenuated. In the presence of recombinant NGAL, IL-1β-induced disturbance in the localization of E-cadherin and ZO-1 was attenuated, and the decrease in TER was partially maintained. These results suggest that NGAL can be used as a biomarker for AKI and that it functions as a protector from AKI.

Fracaso renal agudo. Concepto, definición, epidemiologia, etiopatogenia y clasificación, manifestaciones clínicas, complicaciones y diagnóstico diferencial

Acute renal failure (ARF) is a reversible clinical syndrome caused by the sudden loss of renal function in early stages if the source of the damage is removed. It can be caused by pre-renal causes that compromise renal blood perfusion, which causes parenchymal or interstitial affect glomerular or tubular structures obstructive causes when the urinary excretion is affected. It assumes a common complication in critically ill patients and their conditions more severe forms high mortality, the need for alternative therapies and high health spending. Although the pathophysiology is variable, in case a large number of structural damage coexist level glomeruli and renal tubules. Clinical manifestations depend on the original etiology, including the elevation of nitrogenous products, and often impaired homeostasis, body composition, acid-base balance and catabolism.

Tyrphostins as Potential Therapeutic Agents for Acute Kidney Injury

Acute kidney injury (AKI) is a syndrome characterized by an acute renal cell injury that leads to sudden loss of renal function. There are currently no clinically validated treatments for AKI besides substituting renal function by dialysis. However, new biomarkers will allow an earlier diagnosis, thus providing a window of opportunity for therapeutic intervention. Tyrphostins are a family of compounds originally designed as protein tyrosine kinase inhibitors. However, some molecules of this family have additional actions, such as inhibition of guanylate and adenylate cyclases, mitochondrial uncoupling or antioxidant effects. We review the potential role of tyrphostins in the prophylaxis and treatment of acute kidney injury on the basis of published studies on animals, in vitro experiments and piecemeal information from humans. The AG 490 and AG 126 tyrphostins have recently been shown to protect from AKI in experimental animal models of ischemia-reperfusion and sepsis-induced injury. AG 490 protects from cyclosporin-induced AKI and AG 1714 protects from cisplatin nephrotoxicity. AG 490 is nephroprotective by inhibiting oxidative stress-related Janus activated kinase-2 (JAK2) activation. Potential applications of AG490 or derivative molecules include AKI of nephrotoxic or ischemic nature, or a combination of both, as may occur in the immediate postransplant period. The molecular targets of AG 126 and AG 1714 are less well characterized. In conclusions, different tyrphostins are nephroprotective in animal models of AKI. The characterization of the molecular targets involved will allow the design of novel therapies that may reach the clinical trial stage.

Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications.

Acute renal failure (ARF) can be defined as a sudden loss of renal function and is a common and serious clinical problem. There are many causes of ARF but the most common cause results from injury to the renal tubular epithelial cells (RTECs). RTECs can be injured by schemia or by cytotoxic agents and, once injured, can die by necrosis or apotosis. In general, necrosis occurs in response to any severe injury, which leads to the biochemical collapse of the cell. Milder forms of the same types of injury cause apoptosis. At the cellular level there are fundamental differences between necrosis and apoptosis. Necrosis results from the additive effect of a number of independent biochemical events that are activated by severe depletion of cell energy stores. By contrast, apoptosis occurs via a coordinated, predictable and pre-determined pathway. These biochemical differences between apoptosis and necrosis have important therapeutic implications. Once a cell has been severely injured, necrosis is difficult to prevent. By contrast, the apoptotic pathway can potentially be modulated to maintain cell viability. The components of the apoptotic pathway that are potentially amenable to therapeutic modulation are discussed in detail in this review.