Protective role of alpha-lipoic acid against rhabdomyolysis-induced acute kidney injury in rats.

Objectives: Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats. Materials and Methods: Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins. Results: A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities. Conclusion: Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.

The Development of IgE Multiple Myeloma Following Treatment for Locally Advanced Prostate Cancer.

This case report documents the diagnosis of multiple myeloma (MM) in a 74-year-old man following treatment for locally advanced prostate cancer. It is important to include MM in the differential diagnosis when the patient presents with nonspecific symptoms such as back pain, anemia, and renal impairment in the absence of a prominent increase in prostate-specific antigen (PSA). The present case was diagnosed as IgE MM with a poor prognosis. Prompt diagnosis and intervention of MM is necessary to avoid complications, including renal impairment.

Reno-protective effect of fenofibrate and febuxostat against vancomycin-induced acute renal injury in rats: Targeting PPARγ/NF-κB/COX-II and AMPK/Nrf2/HO-1 signaling pathways.

BACKGROUND: Vancomycin (VCM) is used clinically to treat serious infections caused by multi-resistant Gram-positive bacteria, although its use is severely constrained by nephrotoxicity. This study investigated the possible nephroprotective effect of febuxostat (FX) and/or fenofibrate (FENO) and their possible underlying mechanisms against VCM-induced nephrotoxicity in a rat model. METHODS: Male Wistar rats were randomly allocated into five groups; Control, VCM, FX, FENO, and combination groups. Nephrotoxicity was evaluated histopathologically and biochemically. The oxidative stress biomarkers (SOD, MDA, GSH, total nitrite, GPx, MPO), the apoptotic marker, renal Bcl-2 associated X protein (Bax), and inflammatory and kidney injury markers (IL-1ß, IL-6, TNF-α, Nrf2, OH-1, kappa-light-chain-enhancer of activated B cells (NF-κB), NADPH oxidase, Kim-1, COX-II, NGAL, Cys-C were also evaluated. RESULTS: VCM resulted in significant elevation in markers of kidney damage, oxidative stress, apoptosis, and inflammatory markers. Co-administration of VCM with either/or FX and FENO significantly mitigated nephrotoxicity and associated oxidative stress, inflammatory and apoptotic markers. In comparison to either treatment alone, a more notable improvement was observed with the FX and FENO combination regimen. CONCLUSION: Our findings show that FX, FENO, and their combination regimen have a nephroprotective impact on VCM-induced kidney injury by suppressing oxidative stress, apoptosis, and the inflammatory response. Renal recovery from VCM-induced injury was accomplished by activation of Nrf2/HO-1 signaling and inhibition of NF-κB expression. This study highlights the importance of FX and FENO as effective therapies for reducing nephrotoxicity in VCM-treated patients.

Impact of a Short Educational Session on Early Diagnosis and Management of Acute Kidney Injury for Different Specialties.

AIM AND OBJECTIVE: This questionnaire study aimed to evaluate the impact of a short educational session on the early diagnosis and management of acute kidney injury (AKI) among doctors specializing in fields other than nephrology, assessed through pre- and post-test scores. This educational study included resident doctors from various specialties for assessment. MATERIALS AND METHODS: The study enrolled different specialty resident doctors' departments and assessed them through questionnaires and assessment scores. The pre-test questionnaires were first distributed and collected after 20 minutes. This was followed by a 30-minute short educational lecture on AKI by the nephrology faculty about its early diagnosis and management as per the Kidney Disease Improving Global Outcomes guidelines. Immediately post continuing medical education, the same questionnaires were distributed along with feedback forms and collected after 10 minutes. RESULTS: A total of 110 residents participated in the study. All participants showed significant improvement in the post-lecture questionnaires compared to pre-lecture scores. For medicine and allied branch residents, the pre- and post-lecture scores were significantly higher than those of the surgical and allied branch residents. The lowest score was observed in residents of orthopedics. The improvement scores of all departments also showed significant differences. The highest improvement was seen in the department of gynecology, followed by residents of the critical care unit and the department of anesthesia. The residents of those departments with high pre- and post-test scores had lower improvement scores. CONCLUSION: The study found a significant knowledge gap in different sister specialties in diagnosing and managing AKI. Short educational sessions showed significant improvement in AKI understanding by addressing the knowledge gaps.

The renoprotective effect of Tibolone in sepsis-induced acute kidney injury.

INTRODUCTION: Sepsis-induced acute kidney injury (AKI) remains a major challenge in intensive care, contributing significantly to morbidity and mortality. Tibolone, known for its neuroprotective and hormonal properties, has not been explored for its potential in AKI management. This study investigates the protective effects of Tibolone and its underlying mechanisms involving Sirtuin-1 (SIRT1) and Yes-Associated Protein (YAP) in a rat sepsis model. MATERIALS AND METHODS: Thirty-six female Wistar albino rats underwent cecal ligation and puncture (CLP) to induce sepsis. They were randomly assigned to control, CLP+Saline, and CLP+Tibolone groups. Tibolone was administered intraperitoneally. Biomarkers, including Sirtuin (SIRT1), Yes-associated protein (YAP), Tumor necrosis factor (TNF-α), High mobility group box 1 (HMGB1), malondialdehyde (MDA), creatinine, and urea, were assessed. Histopathological examination evaluated renal damage. RESULTS: Tibolone administration significantly reduced plasma TNF-α, HMGB1, MDA, creatinine, and urea levels compared to the CLP+Saline group. Moreover, Tibolone elevated SIRT1 and YAP levels in kidney tissues. Histopathological examination demonstrated a significant decrease in tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and interstitial inflammation in Tibolone-treated rats. CONCLUSION: This study unveils the protective role of Tibolone against sepsis-induced AKI in rats. The improvements in inflammatory and oxidative biomarkers and histological evidence suggest Tibolone's potential as a therapeutic intervention in sepsis-associated kidney injury. The upregulation of SIRT1 and YAP indicates their involvement in Tibolone's renoprotective mechanisms. Further investigations are warranted to explore Tibolone's translational potential in human sepsis-induced AKI.

Increased risk of acute kidney injury in the first part of an ultra-trail-Implications for abandonment.

Acute kidneys injuries (AKIs) have been described in marathon and trail running. The currently available data allows assessment of before/after comparisons but does not allow an analysis of what happens during the race. A multidisciplinary assessment protocol was performed during the first trail of Clécy (Normandy France) in November 2021. This allowed an initial assay to be carried out, then at the end of each of the 6 loops of 26 km, and finally after 24 h of recovery. The race extends over 156 km in hilly terrain and 6000 m of elevation gain (D+). The level of impairment according to the RIFLE classification was defined for each runner at each assay. Fifty-five runners were at the start, and the per protocol analysis involved 36 runners (27 men and 9 women, 26 finishers). Fifteen (41.7%) of the riders presented at least one result corresponding to a "RIFLE risk" level. After 24 h of rest, only one runner still had a "RIFLE Risk". The distance around the marathon seems to be the moment of greatest risk. For the first time, we find an association between this renal risk and the probability of abandonment. Many runners are vulnerable to kidney damage during long-duration exercise, which is why it's important to limit risk situations, such as the use of potentially toxic drugs or hydration disorders. The consumption of NSAIDs (nonsteroidal anti-inflammatory drugs) before or during an ultra-distance race should therefore be prohibited. Attention should be paid to hydration disorders.

5% Dextrose in Ringer's Lactate versus 5% Dextrose Normal Saline as Maintenance Intravenous Fluid Therapy in Children - A Randomised Controlled Trial.

OBJECTIVES: To estimate the difference in serum chloride levels between children receiving 5% Dextrose in Ringer's Lactate (RLD5) vs. 5% Dextrose Normal Saline (DNS) and to estimate the incidence of dyselectrolytemia, hyperchloremic metabolic acidosis (HCMA), acute kidney injury (AKI) and all-cause mortality in both groups. METHODS: A randomised controlled trial was conducted in non-critically ill children aged 6 mo to 14 y, admitted between August 2021 and July 2022, requiring intravenous fluids. A sample size of 140 was estimated and randomised, with controls receiving 5% DNS and the intervention group receiving RLD5. Kidney function tests and blood gas analysis were done at admission, 24 h and 48 h after starting the maintenance IV fluid, and outcomes were analysed at 24 h and 48 h. Data was collected using a pre-designed data collection form that included demographic and clinical profile details, and outcomes were analysed using SPSS Version 20 software. RESULTS: Seventy-one children per group were enrolled. The mean chloride difference between the two groups at 24 and 48 h were 1.67 (p-value 0.03) and 2.78 (p-value 0.01), respectively. The incidence of AKI at 24 h and 48 h was 1.4% and 2.8% in the RLD5 group and 0% and 1.4% in the DNS group, respectively. At 24 h and 48 h, 2.8% and 2.8% of children had HCMA in the RLD5 group, and 14% and 4.2% had HCMA in the DNS group, respectively. There was no mortality in either group. CONCLUSIONS: Though clinically insignificant, there was a statistically significant difference in the serum chloride levels between the groups.

LncTCONS_00058568 is involved in the pathophysiologic processes mediated by P2X7R in the lower thoracic spinal cord after acute kidney injury.

Acute kidney injury (AKI), a prevalent clinical syndrome, involves the participation of the nervous system in neuroimmune regulation. However, the intricate molecular mechanism that governs renal function regulation by the central nervous system (CNS) is complex and remains incompletely understood. In the present study, we found that the upregulated expression of lncTCONS_00058568 in lower thoracic spinal cord significantly ameliorated AKI-induced renal tissue injury, kidney morphology, inflammation and apoptosis, and suppressed renal sympathetic nerve activity. Mechanistically, the purinergic ionotropic P2X7 receptor (P2X7R) was overexpressed in AKI rats, whereas lncTCONS_00058568 was able to suppress the upregulation of P2X7R. In addition, RNA sequencing data revealed differentially expressed genes associated with nervous system inflammatory responses after lncTCONS_00058568 was overexpressed in AKI rats. Finally, the overexpression of lncTCONS_00058568 inhibited the activation of PI3K/Akt and NF-κB signaling pathways in spinal cord. Taken together, the results from the present study show that lncTCONS_00058568 overexpression prevented renal injury probably by inhibiting sympathetic nerve activity mediated by P2X7R in the lower spinal cord subsequent to I/R-AKI.

[Retracted] Antagonist targeting miR­106b­5p attenuates acute renal injury by regulating renal function, apoptosis and autophagy via the upregulation of TCF4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the EdU staining assay data shown in Figs. 4C and 5C and the western blotting data shown in Fig. 4E were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 169, 2021; DOI: 10.3892/ijmm.2021.5002].

Rhabdomyolysis Following Prolonged Entrapment on a Fence: A Case Report.

It is well documented that prolonged immobilization and heavy alcohol consumption can independently cause rhabdomyolysis; however, entrapment on a fence following alcohol consumption resulting in rhabdomyolysis without prolonged coma or seizures has not been reported. We report a case of a 25-year-old man who, following alcohol consumption, whilst attempting to climb a fence, became entrapped and desperately had to clinch on the fence with both forearms for over three hours, resulting in rhabdomyolysis. This case report highlights the importance of recognizing the potential complications associated with prolonged immobilization and the subsequent management of rhabdomyolysis.

Urolithiasis in Kidney Transplant Patients: A Multicenter KSER Research Series.

Background and Objectives: Urolithiasis occurrence is uncommon in kidney transplantation patients, though it has serious implications, including acute kidney injury in the transplanted kidney. This study investigates the leading causes of urolithiasis in kidney transplantation patients, the diagnostic process, and the outcomes of multimodal management. Materials and Methods: Data collection spanned from January 1997 to December 2021, involving kidney transplantation patients with urolithiasis from the database of the Korean Society of Endourology and Robotics (KSER) research committee. Analysis encompassed factors triggering urolithiasis, the diagnostic process, stone attributes, treatment methods, and outcomes. Results: Our analysis included 58 kidney transplantation patients with urolithiasis from eight medical centers. Of these patients, 37 were male and 4 had previous urolithiasis diagnoses. The mean age was 59.09 ± 10.70 years, with a mean duration from kidney transplantation to diagnosis of 76.26 ± 183.14 months. The most frequent method of stone detection was through asymptomatic routine check-ups (54.7%). Among the 58 patients, 51 underwent stone treatment. Notably, 95.3% of patients with ureter stones received treatment, a significantly higher rate than the 66.7% of patients with renal stones (p = 0.010). Success rates showed no significant differences between renal (70%) and ureter stone (78.0%) groups (p = 0.881). Conclusions: Urolithiasis in transplanted kidneys constitutes an acute condition requiring emergency intervention. Endo-urological interventions are effective for kidney transplantation patients with urolithiasis. To ensure prevention and early detection, diligent follow-up and routine imaging tests are necessary.

Role of renal tubular epithelial cells and macrophages in cisplatin-induced acute renal injury.

Acute kidney injury (AKI) is a clinical syndrome characterized by a sudden and continuous decline in renal function. The drug cisplatin is commonly used as chemotherapy for solid tumors, and cisplatin-induced acute kidney injury (CI-AKI), which is characterized by acute tubular necrosis and inflammation, frequently occurs in tumor patients. Renal tubular epithelial cells (RTECs) are severely damaged early in this process and play an important role in renal tubular injury and the recruitment of immune cells. Macrophages are the most common infiltrating immune cells in the kidney and have a significant impact on CI-AKI and subsequent repair. This article reviews the latest research progress on the effects of RTECs and macrophages on CI-AKI and their interactions in AKI to provide a direction for identifying therapeutic targets for treating AKI.

Successful treatment of peritoneal dialysis for two patients with refractory nephrotic syndrome and acute kidney injury: a case report.

Two patients with refractory nephrotic syndrome were treated with peritoneal dialysis (PD) for diuretic resistance, anasarca and acute kidney injury. Following PD, their fluid overload was promptly alleviated, accompanied by an increase in urine volume and an improvement in renal function. PD as an adjuvant approach enabled them to resume corticosteroids and immunosuppressive agents. Eventually, both patients could be withdrawn from PD and achieved remission of proteinuria.

Acute renal injury after aortic arch reconstruction with cardiopulmonary bypass for children: prediction models by machine learning of a retrospective cohort study.

BACKGROUND: Acute renal injury (AKI) after aortic arch reconstruction with cardiopulmonary bypass leads to injury of multiple organs and increases perioperative mortality. The study was performed to explore risk factors for AKI. We aim to develop a prediction model that can be used to accurately predict AKI through machine learning (ML). METHODS: A retrospective analysis was performed on 134 patients with aortic arch reconstruction with cardiopulmonary bypass who were treated at our hospital from January 2002 to January 2022. Risk factors for AKI were compositive and were evaluated with comprehensive analyses. Six artificial intelligence (AI) models were used for machine learning to build prediction models and to screen out the best model to predict AKI. RESULTS: Weight, eGFR, cyanosis, PDA, newborn birth and duration of renal ischemia were closely related to AKI. By integrating the results of the training cohort and validation cohort, we finally confirmed that the logistic regression model was the most stable model among all the models, and the logistic regression model showed good discrimination, calibration and clinical practicability. Based on 6 independent factors, the dynamic nomogram can be used as a predictive tool for clinical application. CONCLUSIONS: DHCA could be considered in aortic arch reconstruction if additional perfusion of lower body were not performed especially when renal ischemia is greater than 30 min. Machine Learning models should be developed for early recognition of AKI. TRIAL REGISTRATION: ChiCTR, ChiCTR2200060552. Registered 4 june 2022.

Risk factors for mortality in surgical patients on combined continuous renal replacement therapy and extracorporeal membrane oxygenation: single-center retrospective study.

OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.

Ginkgolide A downregulates transient receptor potential (melastatin) 2 to protect cisplatin-induced acute kidney injury in rats through the TWEAK/Fn14 pathway: Ginkgolide A improve acute renal injury.

PURPOSE: In order to seek effective drugs for treating cisplatin-induced acute renal injury and explore the corresponding potential mechanism. METHODS: Mouse kidney injury model was established by intraperitoneal injection of 20 mg/kg cisplatin. The temporal expression of TRPM2 and the regulation of Ginkgolide A on its expression were analyzed by western blot. In order to perform the mechanical analysis, we used TRPM2-KO knockout mice. In this study, we evaluated the repair effect of GA on acute kidney injury through renal function factors, inflammatory factors and calcium and potassium content. Pathological injury and cell apoptosis were detected by H&E and TUNEL, respectively. RESULT: Ginkgolide A inhibited inflammatory reaction and excessive oxidative stress, reduced renal function parameters, and improved pathological injury. Meanwhile, we also found that the repair effect of Ginkgolide A on renal injury is related to TRPM2, and Ginkgolide A downregulated TRPM2 expression and inactivated TWEAK/Fn14 pathway in cisplatin-induced renal injury model. We also found that inhibition of TWEAK/Fn14 pathway was more effective in TRPM2-KO mice than TRPM2-WT mice. CONCLUSION: Ginkgolide A was the effective therapeutic drug for cisplatin-induced renal injury through acting on TRPM2, and TWEAK/Fn14 pathway was the downstream pathway of Ginkgolide A in acute renal injury, and Ginkgolide A inhibited TWEAK/Fn14 pathway in cisplatin-induced renal injury model.

The Role of Vascular Biomarkers in Outcomes of Patients with Kidney Disease.

BACKGROUND: Vascular biomarkers may explain the link between acute kidney injury (AKI) and poor long-term outcomes such as cardiovascular disease (CVD). Vessel injury is exceedingly common in AKI and contributes to the development of kidney fibrosis and CVD. As prominent determinants of vessel stability in the body, angiopoietins and other prominent vascular biomarkers may explain this biological link. SUMMARY: Angiopoietin-1 (Angpt-1) promotes vessel stability by decreasing inflammation, apoptosis, and vessel permeability. By contrast, angiopoietin-2 (Angpt-2) blocks the binding of Angpt-1 to its receptor and thus contributes to vessel instability and permeability. Based on our findings, higher levels of Angpt-1 relative to Angpt-2 were strongly associated with less risk of kidney disease progression, heart failure, and death in hospitalized patients with AKI. In chronic kidney disease patients, it has been shown that endothelial damage in glomerular vasculature triggers Angpt-2 secretion, leading to poor outcomes such as CVD and mortality. Furthermore, in kidney transplant recipients, Angpt-2 levels significantly decrease after transplantation suggesting that transplantation may reduce Angpt-2 levels and decrease rates of poor outcomes. Other vascular health pathways - such as vascular endothelial growth factor and placental growth factor - were associated with improved rates of survival after cardiac surgery in participants with and without AKI. KEY MESSAGES: Vascular health biomarkers provide actionable pathways for clinical intervention in reducing CVD and mortality for AKI patients. There is great need for future research that focuses on developing robust prognostic vascular biomarker panels in order to help identify high-risk AKI survivors who may benefit from targeted follow-up and therapy, with the intention to prevent kidney and cardiac complications.

Restoring glomerular filtration rate by sulforaphane modulates ERK1/2/JNK/p38MAPK, IRF3/iNOS, Nrf2/HO-1 signaling pathways against folic acid-induced acute renal injury in rats.

BACKGROUND: Folic acid (FA)-induced acute renal injury (AKI) is a commonly and highly reproducible model used to study AKI. The current study aims to evaluate the possible protective effects of sulforaphane (SFN) against FA-induced renal damage and explore the underlying molecular mechanism. METHODS: The animals were divided into four groups (6 rats/group) as follows: normal group (received vehicle, p.o.), FA group (received 250 mg/kg, i.p.), SFN low dose group (received 15 mg/kg, p.o. plus FA 250 mg/kg, i.p.), SFN high dose group (30 mg/kg, p.o. plus FA 250 mg/kg, i.p.). At the end of the experiment, serum samples and kidney tissues were obtained to perform biochemical, molecular, and histopathological investigations. RESULTS: The present study showed that FA-caused AKI was confirmed by a significant elevation of kidney function biomarkers serum levels accompanied by an observation of histopathologic changes. Interestingly, SFN-administration significantly improved kidney function, reduced oxidative stress markers; MDA, NADPH oxidase, MPO, iNOS with up-regulation of GSH, GCLM, GPX4, SOD, NQO1, HO-1 and Nrf2 levels. SFN also downregulated proinflammatory markers. The results also demonstrated the anti-apoptotic effect of SFN through its ability to increase the antiapoptotic Bcl-2 protein and to decrease caspase-3. Moreover, SFN significantly decreased the relative expression of JNK, ERK-1/2, IRF3, and p38MAPK as compared to the FA-nephrotoxic group. CONCLUSION: The present study revealed that SFN possess an antioxidant, anti-inflammatory and antiapoptotic activity by modulating caspase-3, Bcl-2, ERK1/2, JNK, GCLM, NQO1, GPX4, Nrf2, HO-1 and P38 signaling pathways in a dose dependent manner which provides a potential therapeutic strategy for preventing FA-induced AKI.