Marker Of Kidney Injury Research Articles

High neutrophil-to-lymphocyte ratio as a cost-effective marker of acute kidney injury and in-hospital mortality after cardiac surgery: a case-control study

Background Inflammation is one of the important pathophysiological characteristics of acute kidney injury (AKI) after cardiac surgery. The aim was to explore the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR), a simple and cost-effective maker of inflammatory response, and AKI after cardiac surgery. Furthermore, whether the NLR affected in-hospital mortality was also investigated. Methods The electronic medical records of patients from January 1, 2006 to December 31, 2018 undergoing cardiac surgery were utilized. The interest outcome was AKI, defined as the criteria of Kidney Disease Improving Global Outcomes (KDIGO), and other outcomes were severe AKI (KDIGO stage ≥2) and in-hospital mortality. Logistic regression was utilized to assess the association of preoperative NLR with outcomes while adjust for potential confounders. Results Totally, 23,638 patients were included. The incidence of AKI was 27.6%. The NLR was significantly greater in patients with AKI compared to those without. As the nonlinear relationship between NLR and AKI indicated by restricted cubic spline, NLR was analyzed as a categorical variable with the cutoff value of five. Multivariate analysis demonstrated that NLR > 5 was significantly associated with an increased risk of AKI, with an odds ratio of 5.046 (95% confidence interval, 4.589 to 5.548), when compared to patients with NLR ≤ 5. Furthermore, high NLR was also an independent risk factor for severe AKI and in-hospital mortality. Conclusions A higher preoperative NLR was increased the risk of AKI, severe AKI, and in-hospital mortality after cardiac surgery, which may be helpful for stratifying patients to develop individualized treatment.

Isoliquiritigenin Prevents the Development of Nephropathy by an HFD in Rats Through the Induction of Antioxidant Production and Inhibition of the MD-2/TLR4/NF-κB Pathway

This study tested the ISL against renal damage induced by a high-fat diet (HFD) and explored its underlying mechanisms. Adult male rats were assigned to four groups: (1) control on a standard diet (STD), (2) ISL on STD (30 mg/kg), (3) HFD, and (4) HFD + ISL (30 mg/kg). After 12 weeks of dietary intervention, ISL treatment led to significant reductions in body weight gain, visceral fat, and glucose and insulin levels in HFD-fed rats. Notably, ISL decreased serum urea and creatinine, increased serum albumin, and improved urinary profiles by lowering the urinary albumin and the albumin/creatinine ratio. Histological analyses revealed that ISL enhanced the glomerular structure and mitigated tubular damage, as evidenced by reduced urinary excretion of the kidney injury markers NGAL and KIM-1. Additionally, ISL significantly lowered cholesterol, triglycerides, and free fatty acids in both the control and HFD groups while also decreasing oxidized low-density lipoproteins (ox-LDLs) and malondialdehyde (MDA). Importantly, ISL enhanced renal antioxidant levels, increasing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Moreover, ISL downregulated mRNA levels of MD-2, Toll-like receptor-4 (TLR-4), and NF-κB, leading to reduced NF-κB p65 levels in renal tissues. In conclusion, ISL offers substantial protection against HFD-induced renal toxicity through mechanisms that attenuate metabolic stress, enhance antioxidant defenses, and inhibit the MD-2/TLR4/NF-κB inflammatory pathway.

Cinnamon Polyphenols Ameliorate the Dysregulation of Cardiac Energy and Autophagic Homeostasis in Rats with Diabetic Cardiomyopathy via the mTOR/PGC1α Pathway

Background Inflammation mediated by hyperglycemia, lipid metabolism disorders, abnormal myocardial energy metabolism, myocardial cell damage, and changes in ventricular structure are important mechanisms in the occurrence and development of diabetic cardiomyopathy (DCM). Cinnamon polyphenols (CP) are extracted from the traditional Chinese medicine cinnamon, which is believed to have cardioprotective effects and has been used in China for hundreds of years. Purpose This study aimed to investigate the therapeutic effects of CP on DCM and its possible mechanisms. Methods The DCM model was established by a single intraperitoneal injection of 85 mg/kg 1% streptozotocin in rats. The treatment group was orally administered 135 mg/kg CP for 28 consecutive days, a dosage verified by experiments on AC16 myocardial cells and detecting liver and kidney injury markers. Results CP could reduce high blood sugar, high blood lipids, left ventricular mass index, levels of myocardial injury markers, adenosine diphosphate (ADP), and cyclic adenosine monophosphate (cAMP) in the model group. It also improved weight loss, and increased myocardial adenosine triphosphate (ATP), adenosine monophosphate (AMP), phosphocreatine (PCr), and ATP/ADP, AMP/ATP, and PCr/ATP ratios. The expression of p-mTOR/mammalian target of rapamycin (mTOR), p62, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in the myocardium of the CP group was enhanced, while the expression of LC3II/LC3I was inhibited. Conclusion CPs can alleviate myocardial damage by reducing blood sugar, blood lipids, and abnormal autophagy levels while promoting the restoration of myocardial energy metabolism homeostasis.

Evaluating anti-inflammatory and anti-oxidative potentialities of the chloroform fraction of Asparagus racemosus roots against cisplatin induced acute kidney injury

Ethnopharmacological relevanceAcute kidney injury (AKI), a global public health concern that increases the risk of death, end-stage renal disease, and prolonged hospital admissions. As of this point, supportive measures like fluid resuscitation and replacement therapy for renal failure are the only treatments available for treating AKI. Asparagus racemosus (AR) also known as Shatavari, belongs to family Liliaceae and is considered exceptional in Ayurvedic medicine due to its versatility in treating and preventing a variety of illnesses. Aim of the studyThe purpose of this study is to determine the effectiveness of chloroform fraction of Asparagus racemosus (CFAR) against cisplatin (CP) induced AKI. Materials and methodsHPLC was used to analyse the presence of bioactive phytocompounds in CFAR using standard quercetin. Further LC-MS study indicated the existence of different bioacive compounds. Normal Rat Kidney (NRK-52E) cells were used to study the nephroprotective effect of CFAR. Cells were untreated, treated or cotreated with CP (20uM) and CFAR (5, 25, 50, 100, 200 and 400μg/ mL) for 24 h. After 24 h of treatment, cell viability assay and assay of apoptosis parameters were performed. The CFAR at the dose of 50mg, 100mg and 200/kg/day was administered orally for 15 days and acute kidney injury was induced in rats by intraperitoneal injection of CP (10mg/kg body weight) at the 10th day of experimentation. Biochemical studies were performed to evaluate kidney function; protein expression by western blot and mRNA expression of related gene were studied from the kidney tissues to evaluate the effects of CFAR. Histopathological analysis was done to investigate the structural abnormalities and fibrosis of renal tissues. ResultOur result reported that CFAR contain many bioactive phytomolecules having many pharmacological properties. Cell viability assay and assay of apoptosis reported that different doses of CFAR could reduced CP-induced cell death and cell apoptosis. The levels of kidney injury markers (BUN, sCr and eGFR), inflammatory markers (Interleukin-18, KIM-1, Cys-C, NF-kB and NGAL), and antioxidant markers (SOD, GSH, CAT, Nrf2 and Bcl2) and lipid peroxidation (MDA) were settled to a normal level by the oral administration of high doses (100 and 200mg/kg body weight) of CFAR after intraperitoneal injection of CP as suggested by biochemical, histopathological, protein and gene expression studies. ConclusionIn conclusion, CFAR at the high doses (100 and 200 mg/kg body weight) could able to protect the kidneys from CP induced oxidative stress and inflammation due to presence of bioactive phytomolecules that prevent the activation of oxidative stress induced signalling cascades leading to kidney damage.

Novel dysregulated long non-coding RNAs in the acute kidney injury-to-chronic kidney diseases transition unraveled by transcriptomic analysis.

Acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition involves a complex pathomechanism, including inflammation, apoptosis, and fibrosis where long non-coding RNAs (lncRNAs) play a crucial role in their regulation. However, to date, only a few lncRNAs have been discovered to be involved in the AKI-to-CKD transition. Therefore, this study aims to investigate the dysregulated lncRNAs in the AKI-to-CKD transition invitro and invivo. To mimic AKI-to-CKD transition both invivo and invitro, bilateral ischemia-reperfusion (IR) kidney injury was performed in Wistar rats (male), and normal rat kidney epithelial cell (NRK52E) cells were treated with exogenous transforming growth factor-β1 (TGF-β1). Further processing and analysis of samples collected from these studies (e.g., biochemical, histopathology, immunofluorescence, and RNA isolation) were also performed, and transcriptomic analysis was performed to identify the dysregulated lncRNAs. Rats subjected to IR showed a significant increase in kidney injury markers (creatinine, blood urea nitrogen (BUN), kidney injury molecule-1(KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) along with altered cell morphology). Apoptosis, inflammation, and fibrosis markers were markedly increased during the AKI-to-CKD transition. Furthermore, transcriptomic analysis revealed 62 and 84 unregulated and 95 and 92 downregulated lncRNAs invivo and invitro, respectively. Additionally, functional enrichment analysis revealed their involvement in various pathways, including the tumor necrosis factor (TNF), wingless-related integration site (Wnt), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. These identified dysregulated lncRNAs significantly contribute to AKI-to-CKD transition, and their knockin/out can aid in developing targeted therapeutic interventions against AKI-to-CKD transition.

High dose of liraglutide impairs renal function in female hypertensive rats.

Glucagon-like peptide-1 (GLP-1) receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. SHR female rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg, LL) and high (0.6 mg/kg, LH) doses. Volume intake and excretion were monitored for a period of 24h. In renal tissue, nitrite-NO2-, nitrate-NO3-, advanced protein oxidation products-AOPP, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. AOPP was reduced only in LL. LH augmented collagen and early markers of kidney injury (blood urea nitrogen-BUN, BUN/Cr). LH increased NO3-, reduced NO2-, and caused an aberrant increase in GFR. Both doses' effects were independent of blood pressure and glycemic control. liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.

Prognostic significance of fibrinogen levels in sepsis-associated acute kidney injury: unveiling a nonlinear relationship and clinical implications.

Fibrinogen plays a pivotal role in the inflammatory cascade and is intricately linked to the pathogenesis of sepsis. Nevertheless, its significance as a prognostic marker for sepsis-associated acute kidney injury (SA-AKI) remains uncertain. This study aimed to investigate the association between fibrinogen levels and 28-day mortality with sepsis-associated acute kidney injury. The fibrinogen levels of patients admitted to the intensive care unit of Beth Israel Deaconess Medical Center between 2008 and 2019 were retrospectively assessed, and those diagnosed with SA-AKI were divided into low, middle and high fibrinogen level groups according to tertiles. Multivariate Cox proportional hazards model was used to assess the 28-day mortality risk of the SA-AKI patients. A total of 3,479 patients with SA-AKI were included in the study. Fibrinogen demonstrated an independent association with 28-day mortality, yielding a hazard ratio (HR) of 0.961 (95% confidence interval [CI]: 0.923-0.999, P = 0.0471). Notably, a non-linear relationship between fibrinogen levels and 28-day mortality was observed, with the threshold observed at approximately 1.6 g/l. The effect sizes and corresponding CIs below and above this threshold were 0.509 (0.367, 0.707) and 1.011 (0.961, 1.064), respectively. Specifically, the risk of mortality among SA-AKI patients decreased by 49.1% for every 1 g/l increment in fibrinogen, provided that fibrinogen levels were less than 1.6 g/l. In patients with SA-AKI, a non-linear relationship was identified between fibrinogen levels and 28-day mortality. Particularly, when their fibrinogen levels were less than 1.6 g/l, a concomitant decrease in 28-day mortality was observed as fibrinogen levels increased.

Association between chronic lead exposure and markers of kidney injury: A systematic review and meta-analysis.

In view of inconsistent reports on the association between chronic lead (Pb) exposure and renal injury markers (potential site of injury), the present systematic review explored their association by reviewing studies that investigated chronic Pb-exposed and those without obvious Pb exposure.Studies reporting blood Pb levels(BLL) and biomarkers of kidney injury [i.e. N-acetyl-β-D-glucosaminidase (NAG), Micro-Globulin(μG) and others] among chronic Pb-exposed and unexposed individuals were systematically searched from digital databases available until February 26, 2024. Preferred Reporting Items of Systematic Reviews and Meta-Analysis Guidelines were adhered to during the execution. Pooled effect size and heterogeneity were estimated using the random effect model and I2 index. The risk of biases & certainty of evidence among the included studies was assessed using the Newcastle Ottawa Scale & GRADE, respectively. Sub-group, sensitivity and meta-regression analyses were performed when data permitted.Pooled quantitative analysis revealed elevated BLL [25.64 (21.59-29.70) µg/dL] Pb-exposed group. The pooled analysis confirmed significantly higher urinary NAG [0.68(0.26-1.10) units], α1μG [3.82(0.96-6.68) mg/g creatinine] β2μG [1.5(0.86-2.14) units and serum creatinine [0.03(0.00-0.05) mg/dL] levels in Pb-exposed group, with high heterogeneity.Current observations indicate the proximal tubular injury as the early and potential site of Pb-induced renal injury. Pb-exposed individuals experience proximal tubular injury (KIM-1, NAG) and dysfunction (β2μG, α1μG, Cystatin-C) prior to obvious clinical renal failure. Present observations should caution the policymakers towards drafting regulations for periodic screening with markers of renal injury and / or dysfunction among those chronically exposed to lead despite the certainty of evidence is very low.

Circulating microRNAs as markers for scrub typhus-associated acute kidney injury.

Circulating microRNAs (miRNAs) are potential biomarkers for various kidney diseases. In this study, we aimed to identify a circulating miRNA signature for detecting acute kidney injury (AKI) in scrub typhus. We prospectively enrolled 40 patients with scrub typhus (20 with AKI, AKI group; 20 without AKI, non-AKI group) and 20 healthy volunteers (the HV group). Thereafter, we performed microarray analysis to assess the serum miRNA profiles of all the participants. Then, to identify miRNAs predictive of scrub typhus-associated AKI, we compared miRNA profiles among these three groups. The proportions of miRNAs, small nucleolar RNAs, and small Cajal body-specific ribonucleoproteins were higher in patients with scrub typhus than in the HVs. Further, relative to the HVs, we identified 120 upregulated and 449 downregulated miRNAs in the non-AKI group and 101 upregulated and 468 downregulated miRNAs in the AKI group. We also identified 11 and 110 upregulated and downregulated miRNAs, respectively, in the AKI group relative to the non-AKI group, and among these miRNAs, we noted 14 miRNAs whose levels were significantly upregulated or downregulated in the AKI group relative to their levels in the HV and non-AKI groups. Biological pathway analysis of these 14 miRNAs indicated their potential involvement in various pathways associated with tumor necrosis factor alpha. We identified miRNAs associated with AKI in patients with scrub typhus that have predictive potential for AKI. Thus, they can be used as surrogate markers for the detection of scrub typhus-associated AKI.

Pre-bypass critical closing pressure predicts acute kidney injury after cardiopulmonary bypass

ObjectivesOptimal blood pressure goals during cardiopulmonary bypass (CPB) remain uncertain and new metrics to individualize perfusion targets are needed. Critical closing pressure (Pcrit) is a fundamental property of the arterial circulation related to vascular tone and represents the outflow pressure impacting flow across the systemic circulation. We examined Pcrit as a prognostic marker of acute kidney injury (AKI). DesignRetrospective cohort study. SettingSingle tertiary care hospital Participants1038 adult cardiac surgery patients that underwent CPB. InterventionsPcrit was calculated using arterial waveform data before initiation of CPB. Pcrit was examined in relation to incidence of stage 2 or higher postoperative AKI according to standard KDIGO definitions. Measurements and Main ResultsOf the 1038 patients included in the study, 50 (5%) experienced AKI. Patients that suffered AKI had significantly higher preoperative risk factors, including higher incidence of severe chronic kidney disease and higher STS risk score (p<0.01). They also had longer operative times and longer cross clamp times (p<0.01). All patients were maintained at similar mean MAP while on CPB. Patients that suffered AKI had a significantly higher pre-bypass Pcrit than those who did not (49.0 vs 44.1 mmHg, p=0.018). In a multivariate regression, Pcrit remained a significant predictor, representing a 16% increased risk of AKI for each 5 mmHg increase in pre-bypass Pcrit (p=0.011). ConclusionsA higher pre-bypass Pcrit is associated with a significantly higher incidence of postoperative AKI. Future study is warranted to investigate using intra-operative Pcrit to determine a personalized blood pressure goal during CPB.

Urinary Cystatin B as a marker of acute kidney injury in cats

Diagnosing acute kidney injury (AKI) might be challenging due to lack of sensitive early markers. The objective of this study was to evaluate the diagnostic and prognostic utility of the urinary biomarker Cystatin B (uCysB) in cats with AKI. Seventy-six client-owned cats were included. Urine samples of healthy cats and cats with various urinary tract disease including urethral obstruction (UO), chronic kidney disease (CKD) and AKI, were collected. uCysB concentration was measured using a research sandwich format ELISA at IDEXX Laboratories, Inc. uCysB was different among groups (P <0.001). uCysB was higher in the AKI (P <0.001) and CKD (P =0.006) groups compared with controls [1052 ng/mL (range, 7–3858) and 112 ng/mL (range, 14–1370) vs. 22 ng/mL (range, 11–154), respectively]. Cats with AKI had higher uCysB compared with cats with CKD (P =0.001) or UO (P =0.004). Receiver operator characteristic curve (ROC) analysis of uCysB as an AKI predictor vs. controls had an area under the curve (AUC) of 0.92 (95 % CI, 0.84–1.0). An 84 ng/mL cutoff point corresponded to sensitivity and specificity of 90 % and 92 %, respectively. uCysB concentration was higher in AKI non-survivors compared with survivors (1572 ng/mL, range, 140–3858 vs. 584 ng/mL, range, 7–2803 respectively; P =0.004). ROC analysis of uCysB as an AKI outcome predictor had an AUC of 0.84 (95 % CI, 0.56–1.0), with an optimal cut-off point of 469 ng/mL, corresponding to sensitivity and specificity of 100 % and 75 % respectively. In conclusion, uCysB is a useful diagnostic and prognostic marker of AKI in cats.

Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults.

We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32±3 years) and nine older (72±3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11±0.11), but the excretion of sucrose was increased only in older adults (Δ1.7±1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65±0.89µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08±0.07mg/dL), cystatin C (group-wide: Δ0.16±0.18mg/L) and urinary IGFBP7×TIMP-2 [group-wide: Δ0.64±0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age.

Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate and mortality in AA-induced CKD mice compared to mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine NGAL, and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared to animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.

KIM-1 and Other Markers of Acute Kidney Injury in Cisplatin-Induced Nephrotoxicity

KIM-1 and Other Markers of Acute Kidney Injury in Cisplatin-Induced Nephrotoxicity

Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis

Background Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD. Methods The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis. Results Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the in vivo animal model and the in vitro cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(ITGB6), a hub and commonly upregulated gene, was upregulated in the in vitro models. Conclusion ITGB6 may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.

The Use of Tissue Markers of Kidney Injury KIM1 and NAG to Compare between Effect of Extra Corporeal Shock Wave Lithotripsy and Retrograde Intrarenal Surgery on Renal Tissue for Early Detection of Kidney Injury in Managing Renal Stone ≤ 2 cm

Abstract Background Retrograde Intrarenal surgery (RIRS) and Extracorporeal shock wave lithotripsy (ESWL) are well-established treatment options for treatment of kidney stones. Kidney injury molecule 1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) are two proteins secreted by the kidney into the urine and have been found to be sensitive markers of acute kidney injury. The aim of this study is to compare between RIRS and ESWL effect on renal tissue and detect early signs of kidney injury by measuring urinary levels of KIM-1and NAG in patients with kidney stone who were treated by ESWL and RIRS. Objective To compare between effect of ESWL and RIRS on renal tissue and detect early signs of AKI through using new biomarkers for AKI (KIM-1, NAG) in managing renal stone ≤ 2 cm Patients and Methods This prospective randomized study was conducted in urology department Ain Shams university hospitals and in urology department of Theodor Bilharz Research Institute hospital during the period from 4/2022 till 4/2023 after obtaining Ain Shams university ethics committee approval (No. FWA 000017585). Results This study revealed highly statistically significant increased 24-hour post-operative KIM-1/Cr and NAG/Cr in group A (ESWL) (4.59 ± 0.94) and (0.22 ± 0.04) when compared with group B (RIRS) (2.22 ± 0.65) and (0.13 ± 0.03). In group A (ESWL) there was high statistically significant increase in 24-hour post-operative KIM-1/Cr (4.59 ± 0.94) and NAG/Cr (0.22 ± 0.04) when compared with pre-operative KIM-1/Cr (2.26 ± 0.45) and NAG/Cr (0.12 ± 0.04), while in group B (RIRS) there was only statistically significant increased 24-hour post-operative NAG/Cr (0.13 ± 0.03) when compared with pre-operative NAG/Cr (0.11 ± 0.03) with no statistical significant difference between pre-operative KIM-1/Cr (2.22 ± 0.51) and 24-hour post-operative KIM-1/Cr (2.22 ± 0.65). Conclusion Patients with known renal impairment or decreased renal functions suffering from renal stone ≤ 2 cm we recommend management of stone using RIRS over ESWL and in case of ESWL being the only option we recommend use of lower number of shock waves per setting.

Sorghum bicolor polyphenol-rich extract improves insulin sensitivity and protect against chronic stress exacerbated diabetic nephropathy through modulation of Nrf2/NF-κB

IntroductionSorghum bicolor leaf sheath is known for its rich phytoconstituents 3-in deoxyanthocyanidins with protective and health benefits in targeting oxidative stress, inflammation and apoptosis. This study aimed to investigate Sorghum bicolor polyphenol-rich extract (SBPE) and its combination with metformin on insulin resistance and diabetic nephropathy in high-fat/streptozotocin-induced diabetic rats exposed to chronic stress. MethodsAntidiabetic and nephroprotective effects of SBPE was investigated in male Wistar rats fed with high-fat diet and injected streptozotocin (35 mg/kg) intraperitoneally. Diabetic rats were exposed to chronic unpredictable mild stress and orally treated with SBPE (200 mg/kg), metformin (250 mg/kg) and SBPE + metformin for 28 days. Kidney function parameters, FBS, insulin, adiponectin, kidney injury marker (KIM-1), triglycerides were determined. Renal tissues inflammatory (TNF-α, IL-1β, IL-10), oxidative stress, apoptotic (caspase-3,-9) and transcriptional factors (Nrf2 and NF-κB) were determined as well as histology. ResultsSBPE significantly reduced FBS, triglycerides insulin and parameters for insulin resistance in diabetic rats exposed to stress. Dysregulated electrolytes, urea, creatinine, adiponectin and KIM-1 were significantly reversed in SBPE and SBPE + metformin groups. SBPE treatment significantly reduced MDA, nitrites, TNF-α, and IL-1β levels, while GSH, catalase, SOD, GST and IL-10 were increased in renal tissues. Increased apoptotic markers (caspase-3, caspase-9) and NF-κB, along with reduced Nrf2 levels, were significantly reversed by SBPE and SBPE + metformin. Distorted kidney histomorphoarchitecture was reversed in SBPE-treated groups. ConclusionSorghum bicolor polyphenol-rich extract and its combination with metformin showed promising antidiabetic effects in stress-exacerbated diabetes in rats through improving insulin sensitivity and nephroprotective mechanisms.

Tissue Inhibitor of Metalloproteinase 2 and Insulin-Like Growth Factor-Binding Protein 7 in Pediatric Diabetic Ketoacidosis

Abstract Background Diabetic ketoacidosis (DKA) is one of the main causes of end-stage kidney disease (ESKD). Urinary concentration of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are well known urinary acute kidney injury (AKI) biomarkers. Objectives to determine the level of urinary TIMP-2 and IGFBP7 as markers of acute kidney injury (AKI) in children with T1DM during and after the resolution of diabetic ketoacidosis. Patients and Methods A prospective longitudinal study was conducted over 1 year, where we have included children with T1DM presented to Emergency Department (ED) at Children’ s Hospital, Faculty of Medicine, Ain Shams University, with moderate and severe DKA, where we followed them at presentation and day 14, and determined those who developed AKI and measured urinary TIMP-2 and IGFBP7 to detect it AKI. Results We have included 40 pediatric patients with T1DM with mean (±SD) age of 10.59 ± 2.17 years, with a female predominance (90%). Among our patients, 18 patients (45%) had AKI at presentation, where they had a significantly elevated urinary level of both TIMP-2 and IGFBP7 than without AKI (TIMP-2 (ng/ml):112.58(13.76 - 190.1) versus 33.53 (17.27 - 149.65), IGFBP7(ng/ml) :77.42(0.57 - 164.3) versus 1.41(0.67 - 82.63) (p &amp;lt; 0.001). Follow up at day 14, after recovery from DKA, we had no patients with AKI, with significant decrease in the same urinary biomarkers (TIMP-2(ng/ml) :11.35 (8.13 - 25.03) versus 9.62 (7.67 - 17.02), IGFBP7(ng/ml) :0.94(0.51 - 2.34) versus 0.78 (0.43 - 1.34) (p &amp;lt; 0.005). Conclusion The level of urinary TIMP-2 and IGFBP7 increased in children and adolescent with T1DM who developed AKI at the time of presentation of DKA, and normalized after the resolution of DKA and the recovery from AKI.

Urinary Podocin as a Noninvasive Marker of Kidney Injury in New-Onset Diabetes after Kidney Transplantation

Urinary Podocin as a Noninvasive Marker of Kidney Injury in New-Onset Diabetes after Kidney Transplantation

Analysing the influence of dapagliflozin on urinary tract infection vulnerability and kidney injury in mice infected with uropathogenic Escherichia coli.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors have revolutionized clinical medicine, but their association with urinary tract infection (UTI) risk remains debated. This study investigates the influence of dapagliflozin on UTI outcomes, focusing on kidney injury. Female non-diabetic C57BL/6J and C3H/HeOuJ mice, along with diabetic db/db mice, were orally administered dapagliflozin (1 mg/kg or 10 mg/kg) for 7 days before transurethral uropathogenic Escherichia coli (UPEC) infection. Mice were killed either 24 h after UTI or after six additional days of dapagliflozin treatment. UPEC titers were enumerated, and kidney histopathology, injury, fibrosis and function were assessed. Vehicle- and dapagliflozin-treated C57BL/6J mice exhibited similar urine and bladder UPEC titers, with minimal kidney burden 24 h after UTI. In C3H/HeOuJ mice, UPEC burden was comparable in vehicle- and 1 mg/kg dapagliflozin-treated groups both 24 h and 7 days after UTI. However, C3H/HeOuJ mice receiving 10 mg/kg dapagliflozin had increased UPEC titers in the urine, bladder and kidneys at both endpoints. Kidney injury and fibrosis markers, as well as kidney function, were similar in vehicle and dapagliflozin groups. In diabetic db/db mice receiving dapagliflozin, UPEC strain UTI89 titers were reduced 7 days after UTI compared to vehicle-treated mice, but no difference in UPEC titers was observed when mice were infected with UPEC strain CFT073. Kidney injury and fibrosis markers and kidney function remained similar across treatment groups. Dapagliflozin does not consistently influence UTI susceptibility and shows limited impact on kidney injury or fibrosis, suggesting SGLT2 inhibitors have minimal effects on UTI-related kidney complications.