Elevated Serum Creatinine Research Articles

Neurological Manifestation of Neonatal Acute Kidney Injury: Focusing on the Clinico-Radiological Profile.

Purpose This study aimed atstudying the neurological manifestation of neonatal acute kidney injury, focusing on the clinico-radiological profile. Methodology In this cross-sectional study, newborns hospitalized in the neonatal intensive care unit of a tertiary care hospital were enrolled over a study period of one year. As per the Kidney Disease: Improving Global Outcome (KDIGO) criteria, 74 neonates were enrolled, and magnetic resonance imaging (MRI) was performed on the same neonates. Result In this study, acute kidney injury (AKI) was seen more often in neonates with admission weights between 1,500 and 2,499 grams, accounting for 52.7% of total study participants. In the current study, neonates admitted with AKI presented more with signs and symptoms of encephalopathy, such as lethargy (78.4%), seizures (64.8%), and irritability (35.1%) at admission. Signs and symptoms of fever and decreased urine output were more common after the first week of life. Abnormal MRI findings were observed in 64.9% of neonates with AKI. The mean blood urea and serum creatinine levels in neonates with abnormal MRI were 188.14 ± 108.25 mg/dL and 2.93 ± 2.16 mg/dL, respectively. The mean blood urea and serum creatinine levels in neonates with normal MRI were 169.84 ± 65.45 mg/dL and 2.41 ± 1.85 mg/dL, respectively. Of the 74 neonates enrolled with AKI, 12 (16.21%) had CSVT. These neonates had a mean blood urea level of 231.58 ± 111.66 mg/dL (p = 0.047) and a mean creatinine level of 3.77 ± 2.78 mg/dL. Conclusion Neonatal AKI has a variable presentation with high mortality and morbidity. Elevated serum urea and creatinine can be used to predict CSVT.

Ten-year outcomes of hybrid coronary revascularization at a single center.

Hybrid coronary revascularization (HCR) is a well-established technique for treating multi-vessel coronary disease. There remains a paucity of discussion assessing the efficacy of HCR with respect to the timing of the surgical component relative to that of the percutaneous coronary intervention (PCI). A retrospective review was undertaken of our prospectively collected database from January 2009 to December 2019. Of 395 HCR patients analyzed, we examined the outcomes of 109 pairs of propensity-matched patients who either underwent robotic-assisted minimally-invasive direct coronary artery bypass (MIDCAB) first, or who had PCI prior to surgery. Thirty-day mortality was 0.25% (1 death) for the entire cohort. Mid-term survival for the total 'MIDCAB-first' group was 94.1% (17 deaths), not significantly different to that for the 'PCI-first' cohort (8 deaths, 92.7%), and this was also statistically comparable after propensity matching. Perioperative morbidity was not different between patient groups. Freedom from major adverse cardiac and cerebrovascular events (MACCE) and the incidence of repeat revascularization was similar between the two groups at up to 11-year follow-up. Elevated serum creatinine independently predicted increased MACCE for all patients, irrespective of the sequence of HCR revascularization employed. In appropriately selected patients with multi-vessel coronary disease, HCR is associated with excellent short and longer-term results, irrespective of whether the MIDCAB or PCI procedure is performed first.

Prophylactic and curative activity of Withania somnifera on experimentally induced calcium oxalate nephrolithiasis

Withania somnifera an ayurvedic herb was utilized to assess the antilithic properties of calcium oxalate (CaOx) Nephrolithiasis in rats fed ethylene glycol (EG) in an experimental setting. There were 5 groups of animals (n = 6). The control group was given normal saline, Lithiatic control was given ethylene glycol 1% (v/v) with ammonium chloride 1% (w/v) for 4 days (received stone inducing treatment till 28th day ), follow by 1% ethylene glycol alone in water, Standard group received antiurolithiatic drug (Cystone) (500 mg/Kg) from 15th day till 28th day, treatment group received Withania somnifera methanolic extract (200 mg/Kg) from 15th day till 28th day (Curative regimen) and received Withania somnifera methanolic extract (WS-200 mg/Kg) from 1st day till 28th day (prophylactic regimen) in wistar rats. Blood and kidney tissue were collected after the 28th day of urine. Ca2-, Mg2+, K+ and PO4- levels were estimated in urine, creatinine and urea level were estimated in serum whereas all oxidative stress was measured in kidney tissue. Additionally, Urinary microscopy and kidney histopathology were estimated. Lithiatic control group showed significant elevation (P<0.0001 vs. control) in serum creatinine, blood urea and antioxidants levels. Due to crystal deposits, the histopathology of Lithiatic group showed tubule dilatation with interstitial inflammatory infiltrate, whereas the therapy group showed less tubule dilatation with interstitial inflammatory infiltrate. It can be concluded that at 200 mg/kg the herbal drug possessed significant potential in the management of nephrolithiasis.

Risk factors for acute kidney injury and impact of earlier anticoagulation on renal function in patients with normotensive pulmonary embolism: a retrospective cohort study

ObjectiveWe aimed to investigate the risk factors for acute kidney injury (AKI) after normotensive pulmonary embolism (PE) and the impact of anticoagulation on renal recovery.DesignMulticentred, retrospective cohort study.SettingData from four...

Diagnosing the Recent Decrease in Utilization of Deceased Donor Kidneys.

The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250-nautical-mile circles implemented on March 15, 2021 (KAS250). Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19. In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant. The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant.

Recurrent acute kidney injury with Fanconi syndrome related to red yeast rice supplement.

A 51-year-old woman was admitted to our hospital for acute kidney injury (AKI) with an elevated serum creatinine level of 5.07mg/dL and Fanconi syndrome. The patient was discharged after partial recovery of kidney dysfunction with conservative treatment but was readmitted approximately three months later due to a recurrence of AKI with Fanconi syndrome. A kidney biopsy revealed findings consistent with acute tubular necrosis and localized tubulointerstitial nephritis, with no specific vascular or glomerular lesions. The patient's medical history revealed that prior to both AKI episodes, the patient had been taking "Red Yeast Cholestehelp", a lipid-lowering supplement for a period of time. Her kidney dysfunction and Fanconi syndrome improved with the discontinuation of the supplement and correction with oral medications. In Japan, a series of similar health hazards related to the red yeast rice supplement has been reported, but the causative toxin and its causal relationship with AKI have not been established. The present case provides firm evidence that clinically supports this relationship.

Predictive value of combining urinary N-acetyl-β-D-glucosaminidase and serum homocysteine for contrast-induced nephropathy in patients after percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) can lead to serious complications following percutaneous coronary intervention (PCI). Urine N-Acetyl-β-D-glucosaminidase (uNAG) and serum homocysteine (sHCY) are both potential predictors for CIN detection, but their combination has not been explored. We aimed to combine uNAG and sHCY as predictors for the early detection of CIN and for prognosis prediction in patients after PCI. A total of 232 consecutive patients who underwent PCI at a university hospital were recruited for this study. According to the European Society of Urology and Reproduction (ESUR) criterion, CIN is defined as an elevation of serum creatinine (sCr) by ≥25% or ≥0.5 mg/dl from baseline within 48 h. We assessed the use of individual biomarkers (uNAG and sHCY) measured around PCI and their combinations for CIN detection and prognosis prediction. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to evaluate the predictive efficiency of potential predictors. In total, 54 (23.28%) patients developed CIN. Concentrations of uNAG and sHCY increased significantly in CIN subjects (p < 0.05) than non-CIN. CIN could be predicted by uNAG and sHCY but not by creatinine at an early stage. At pre-PCI, 0, 12, 24, and 48 h after PCI, the AUC-ROC value of uNAG in calculating total CIN was 0.594, 0.603, 0.685, 0.657, and 0.648, respectively. The AUC-ROC value of sHCY in calculating total CIN was 0.685, 0.726, 0.771, 0.755, and 0.821, respectively. The panel of uNAG plus sHCY detected CIN with significantly higher accuracy than either individual biomarker alone and earlier than sCr. For detecting total CIN, this panel yielded AUC-ROCs of 0.693, 0.754, 0.826, 0.796, and 0.844 at pre-PCI, 0, 12, 24, and 48 h after PCI, respectively, which were superior to those of the individual biomarkers. For predicting the incidence of major adverse cardiovascular events (MACE) within 30 days to 12 months, the AUC-ROC values for uNAG and sHCY measured before discharge were 0.637 and 0.826, respectively. The combined panel yielded an AUC-ROC of 0.832. The combined detection did not significantly enhance the predictive capability for MACE in patients with CIN. The CIN group and the non-CIN group showed no significant difference in the Coronary Heart Disease Intensive Care Unit (CCU) stay time, hospital stay time, demand for renal replacement therapy, CCU mortality rate, and in-hospital mortality rate. The uNAG and sHCY panel demonstrated better sensitivity and specificity for predicting the diagnosis and prognosis of CIN in patients after PCI, earlier than sCr. The combination of these biomarkers revealed a significantly superior discriminative performance for CIN detection and prognosis compared to using uNAG or sHCY alone.

A Mild Increase in Serum Creatinine after Surgery Is Associated with Increased Mortality.

Background: Acute kidney injury (AKI), a prevalent postoperative complication, predominantly manifests as stage 1, characterized by a mild elevation in serum creatinine (SCr). There is yet to be a consensus regarding the association between stage 1 AKI and adverse outcomes in surgical patients. Methods: This retrospective study enrolled adult patients who underwent at least one surgery during hospitalization from the MIMIC IV database. AKI was diagnosed when the KDIGO creatinine criteria were satisfied within 7 days after surgery. Stage 1a AKI was defined as an absolute increase in SCr of 26.5 μmol/L, and stage 1b was defined as a 50% relative increase. Stage 1 AKI was also divided into transient and persistent substages based on whether the AKI recovered within 48 h after onset. The association between stage 1 AKI and its substages and in-hospital mortality was evaluated. Results: Among 49,928 patients enrolled, 9755 (19.5%) developed AKI within 7 days after surgery, of which 7659 (78.5%) presented with stage 1 AKI. The median follow-up was 369 (367, 372) days. Stage 1 AKI was significantly associated with in-hospital mortality after adjustment (aHR, 2.73; 95% CI, 2.29, 3.26). Subgroup analyses showed that the risk of stage 1 AKI on in-hospital mortality was attenuated by age ≥ 65 years (p for interaction = 0.017) or a baseline eGFR < 60 mL/min per 1.73 m2 (p for interaction = 0.001). Compared with non-AKI, patients with stage 1b (aHR, 3.06; 95% CI, 2.56, 3.66) and persistent stage 1 (aHR, 2.03; 95% CI, 1.61, 2.57) AKI had an increased risk of in-hospital mortality; however, this risk was not significant in those with stage 1a (aHR, 1.01; 95% CI, 0.68, 1.51) and transient stage 1 (aHR, 1.11; 95% CI, 0.79, 1.57) AKI. Conclusions: Stage 1 AKI exhibits an independent correlation with a heightened mortality risk among surgical patients. Consequently, a tailored adaptation of the KDIGO AKI classification may be necessitated for the surgical population, particularly those presenting with decreased baseline kidney function.

Farnesol attenuates cadmium-induced kidney injury by mitigating oxidative stress, inflammation and necroptosis and upregulating cytoglobin and PPARγ in rats

Heavy metals are environmental pollutants that can harm animals and humans even at low concentrations. Cadmium (Cd) is known for its serious health effects on different organs and its toxicity is associated with oxidative stress (OS) and inflammation. Farnesol (FAR), a sesquiterpene alcohol found in many vegetables and fruits, possesses promising anti-inflammatory and antioxidant activities. This study evaluated the effect of FAR on Cd-induced kidney injury, pinpointing its effect of the redox status, inflammation, fibrosis and necroptosis. Rats in this study received FAR for 14 days and Cd on day 7. Elevated serum creatinine, urea and uric acid, and several kidney histopathological alterations were observed in Cd-administered rats. Cd increased MDA, decreased antioxidants, downregulated PPARγ and upregulated NF-κB p65, IL-6, TNF-α, and IL-1β. Necroptosis mediators (RIP1, RIP3, MLKL, and caspase-8) and α-SMA were upregulated, and collagen deposition was increased in Cd-administered rats. FAR ameliorated kidney injury markers and tissue damage, attenuated OS, suppressed NF-κB and inflammatory mediators, and enhanced antioxidants. In addition, FAR suppressed RIP1, RIP3, MLKL, caspase-8, and α-SMA, and enhanced kidney cytoglobin and PPARγ. In conclusion, FAR protects against Cd nephrotoxicity by suppressing OS, inflammatory response and necroptosis, effects associated with enhanced antioxidants, cytoglobin, and PPARγ.

Insomnia and sleep duration for kidney function: Mendelian randomization study

Objectives Extensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR). Methods Independent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate. Results MR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected. Conclusions This study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

Peri- and postoperative morbidity and mortality in older patients with non-small cell lung cancer: a matched-pair study

BackgroundReports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors.MethodsWe identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015. A matched-pair analysis was performed on 227 older patients and corresponding 227 younger patients. Short-term surgical outcomes were postoperative morbidity, length of hospital stay, 30-day and 90-day mortality. Long-term operative outcomes were disease-free and overall survival.Results454 patients were included in the matched-pair analysis. 36% of younger patients developed postoperative complications versus 42% in older patients (p = 0.163). Age was not significantly associated with the occurrence of postoperative complications. Median length of hospital stay was 14 days in older patients and 13 days in younger patients (p = 0.185). 90-day mortality was 2.2% in younger patients compared to 4% in older patients (p = 0.424). In patients aged 75 and older impaired performance status (ECOG ≥ 1) was associated with decreased overall survival (HR = 2.15, CI 1.34–3.46), as were preoperative serum C-reactive protein / albumin ratio ≥ 0.3 (HR = 1.95, CI 1.23–3.11) and elevated preoperative serum creatinine levels ≥ 1.1 mg/dl (HR = 1.84, CI 1.15–2.95). In the younger cohort male sex (HR = 2.26, CI 1.17–4.36), postoperative stage III disease (HR 4.61, CI 2.23–9.54) and preoperative anemia (hemoglobin < 12 g/dl) (HR 2.09, CI 1.10–3.96) were associated with decreased overall survival.ConclusionsLung resection for NSCLC in older patients is associated with postoperative morbidity and mortality comparable to those of younger patients. In older patients, physical activity, comorbidities and nutritional status are related to survival and should influence the indication for surgery rather than age alone.

Ameliorating and Therapeutic Impact of Curcumin Nanoparticles Against Aluminum Oxide Nanoparticles Induced Kidney Toxicity, DNA Damage, Oxidative Stress, PCNA and TNFα Alteration in Male Rats.

Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.

Peak Serum Creatinine as a Biomarker of Pancreatic Necrosis in Acute Pancreatitis: A Cross-Sectional Study

Pancreatitis is the inflammation of the pancreas. Pancreatitis can result in pancreatic necrosis which may lead to significant morbidity and mortality. It is possible to predict pancreatic necrosis and organ dysfunction using many biochemical indicators and markers. Peak serum creatinine has been identified as one of such useful markers to predict pancreatic necrosis. Objective: To find the diagnostic accuracy of elevated peak serum creatinine as a predictor of pancreatic necrosis in patients with acute pancreatitis taking the contrast-enhanced computed tomogram scan (CECT) as the gold standard and to establish the degree of agreement between the two clinical tests. Methods: A cross-sectional, analytical study that was carried out at the Department of Surgery, Benazir Bhutto Hospital, Rawalpindi from January 2020 to January 2023. 150 patients diagnosed as having pancreatitis were enrolled in the study. Peak serum creatinine at 48 hours &gt; 1.8 mg/dl was labeled as a predictor of pancreatic necrosis. Contrast-enhanced computed tomogram scan was done within 96 hours of admission. The pancreatic necrosis suggested by raised serum creatinine was confirmed by CECT. The diagnostic accuracy of peak serum creatinine and the degree of agreement between the two modalities was calculated. The Kappa coefficient was used to calculate the strength of agreement. Results: The results show that Peak serum creatinine has a sensitivity of 45.5%, specificity of 97.35%, PPV of 85.0 %, NPV of 93.8 %, and accuracy of 84.6%. This study found that the degree of agreement between raised peak serum creatinine levels and CECT to predict pancreatic necrosis was 84.7% with a “Kappa coefficient” of 0.51. Consequently, the null hypothesis was rejected in light of these findings. Conclusions: It was concluded that elevated serum creatinine (SCr &gt;1.8 mg/dl) at 48 h of admission can be used as a predictor of pancreatic necrosis in patients with acute pancreatitis.

Clinical outcomes in paediatric tubulointerstitial nephritis and uveitis syndrome (TINU).

To evaluate the clinical presentation, course, and outcomes of uveitis in paediatric patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Multicentric Retrospective Cohort Study 110 patients ≤21 years of age diagnosed with TINU from 10 sites across the United States and Canada. Clinical diagnosis of TINU required uveitis diagnosed by an ophthalmologist, elevated serum creatinine (SCr) and elevated urine β2-microglobulin (β2M) or abnormal urinalysis. Renal biopsy and systemic illness were not mandatory. Univariate and multivariate analysis was performed to analyse risk factors and treatment modalities. Median age was 13 years (Range (5.9-18.4); 52% male); median follow-up, 1.6 years (IQR 0.98-4.02). Uveitis was symptomatic in 90%, with bilateral anterior uveitis in 94%. Ninety-two (84%) patients required immunomodulatory treatment (IMT). Methotrexate (n = 44) and mycophenolate mofetil (n = 39) were the first agents after oral corticosteroids. 45% required addition of biologic agents (Adalimumab [n = 33], Infliximab [n = 8]). Younger age (p = 0.018), male sex (p = 0.011), and higher uveitis grade at presentation (p = 0.031) were associated with greater IMT ( ≥ 2) requirement. 53% had uveitis recurrence compared to 16% with nephritis recurrence. At the most recent visit, nephritis was controlled in 90%, while uveitis in 74%. Four (4%) patients required glaucoma surgery. Nine (8%) patients had renal complications. Most patients with TINU require steroid-sparing IMT for control of uveitis, with nearly half requiring addition of biologic agents. Urinalysis, urine β2M and SCr testing should be considered in children presenting with uveitis, especially when the disease is bilateral and anterior.

Association of the podocyte phenotype with extracapillary hypercellularity in patients with diabetic kidney disease.

Extracapillary hypercellularity was recently identified as a poor prognostic factor for diabetic kidney disease (DKD), but its nature, pathogenesis, and relationship with glomerular sclerosis are still unclear. We retrospectively studied 107 patients with biopsy-proven DKD, recruited from January 2018 through December 2020. We compared the clinicopathologic characteristics of 25 patients with extracapillary hypercellularity lesions (the extracapillary hypercellularity group) to those of 82 patients without extracapillary hypercellularity (the control group). Multiple cell-specific markers were used for immunohistochemical staining to analyse the types of cells that exhibited extracapillary hypercellularity. Podocyte phenotype changes were evaluated via immunohistochemical staining for Synaptopodin and Nephrin, and foot process width was measured via transmission electron microscopy. Patients with extracapillary hypercellularity lesions had more severe clinical features than patients without extracapillary hypercellularity in DKD, as indicated by elevated proteinuria and serum creatinine levels, and decreased serum albumin. Pathologically, extracapillary hypercellularity was accompanied by increased mesangial hyperplasia and interstitial fibrosis. Severe obliterative microvascular disease was observed more frequently in the extracapillary hypercellularity group than in the control group. At cell type analysis, 25 patients in the DKD-extracapillary hypercellularity group showed that a mixture of cells expressed either Wilm's tumor-1 or paired box protein 2. Furthermore, DKD-extracapillary hypercellularity patients had significant loss of podocyte phenotype and severe foot process effacement. Cells in extracapillary hypercellularity had increased hypoxia-induced factor-1 alpha expression. Extracapillary hypercellularity is associated with severe renal dysfunction and renal sclerosis. Vascular damage is closely related to severe podocyte hypoxia injury and requires additional attention in future research.

Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.

2,5-Dihydroxyacetophenone attenuates acute kidney injury induced by intra-abdominal infection in rats.

As one of the most serious complications of sepsis, acute kidney injury (AKI) is pathologically associated with excessive inflammation. 2,5-Dihydroxyacetophenone (DHAP) is isolated from Radix rehmanniae praeparataand exhibit potent anti-inflammatory property. This research aimed at determining the role of DHAP in sepsis-associated AKI (SA-AKI) and the underlying mechanism. Plasma creatinine (Cre), blood urea nitrogen (BUN), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels of SA-AKI patients were detected to evaluate their clinical characteristics. SA-AKI rat models were established by using caecum ligation puncture (CLP) surgery. CLP-induced rats were administered via oral gavage with 20 or 40 mg DHAP after 2 h of CLP surgery. Subsequently, survival rates, serum indexes, histopathological changes, inflammatory factors, renal function indexes and extracellular regulated protein kinases (ERK) and nuclear factor-κB (NF-κB) signalling pathways were detected. SA-AKI patients exhibited markedly higher levels of plasma Cre, BUN, TNF-α and IL-1β than healthy people. Compared with sham rats, CLP-induced septic rats showed significantly decreased survival rate, increased serum lactate dehydrogenase activity and serum lactate level, obvious renal histopathological injury, upregulated TNF-α, IL-1β and TGF-β1 levels, elevated serum creatinine, BUN and serum cystatin C concentrations, serum neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels and reduced renal artery blood flow. All the above CLP-induced changes in septic rats were mitigated after DHAP administration. Additionally, CLP-induced elevation in phosphorylated-ERK1/2 and nuclear NF-κB p65 protein levels was inhibited by DHAP treatment. DHAP hinders SA-AKI progression in rat models by inhibiting ERK and NF-κB signalling pathways.

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

The impact of acute kidney damage in the community.

Assess incidence of Acute Kidney Diseas and Disorders (AKD) and Acute Kidney Injury (AKI) episodes and impact on progression of renal dysfunction and risk of all-cause mortality in the community. Community of 1863731 aged>23 years with at least two serum creatinine measurements. eGFR was calculated using CKD-EPI formula. CKD, AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The sCr values and RIFLE scale was used to classify episodes. Progression of renal dysfunction and mortality were evaluated. 56850 episodes of AKD in 47972 patients in 4.8 years were identified. AKD incidence of AKD was 3.51 and 12.56/1000 patients/year in non-CKD and CKD, respectively. One AKD episode was observed in 87.3% patients, two in 9.3% and three or more in 3.4%. A second episode was less common in patients without CKD (10.3%) compared to those with CKD (18.4%). Among patients without CKD a total of 43.8% progressed to CKD, and those with previous CKD 63.1% had eGFR decline of>50%. The risk of progression to CKD was higher in women, older, overweight-obesity and heart failure, as was the risk of eGFR decline>50% in CKD patients, although the number of AKD episodes was also a risk factor. AKI episodes were observed in 5646 patients with or without CKD. Of these, 12.7% progressed to CKD and of those with pre-existing CKD, 43.2% had an eGFR decline of>20%. In the toal population mortality within 3 months of detection of AKD episode occurred in 7% patients, and was even higher in patients with AKI, 30.1%. Acute elevations in serum creatinine in the community may pose a health risk and contribute to the development of CKD. Identification of therapeutic targets and provision of appropriate follow-up for those who survive an episode is warranted.

High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis

To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury (IRI) and its regulatory role in IRI. C57BL/6 mice were divided into sham operation group, IRI (induced by clamping the renal artery) model group, IRI+DMSO treatment group, and IRI+SN-011 treatment group. Serum creatinine and blood urea nitrogen of the mice were analyzed, and pathological changes in the renal tissue were assessed with PAS staining. RT-qPCR, ELISA, Western blotting, and immunohistochemistry were used to detect the expression levels of STING, KIM-1, Bcl-2, Bax, caspase-3, TLR4, P65, NLRP3, caspase-1, CD68, MPO, IL-1β, IL-6, and TNF-α in the renal tissues. In the cell experiment, HK-2 cells exposed to hypoxia-reoxygenation (H/R) were treated with DMSO or SN-011, and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR, Western blotting or flow cytometry. In C57BL/6 mice, renal IRI induced obvious renal tissue damage, elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1, STING, TLR4, P65, NLRP3, caspase-1, caspase-3, Bax, CD68, MPO, IL-1β, IL-6, and TNF-α, and reduction of Bcl-2 expression level. Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes. In HK-2 cells, H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate, which was significantly lowered by treatment with SN-011. Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.