Marker Of Acute Kidney Injury Research Articles

Effect of Ibuprofen on Markers of Acute Kidney Injury, Intestinal Injury, and Endotoxemia after Running in the Heat.

To test the hypothesis that ibuprofen ingestion exacerbates markers of acute kidney injury (AKI), gastrointestinal (GI) injury, and endotoxemia after running in the heat. Using a randomized double-blind crossover design, eleven physically active individuals (six women) ingested 600 mg of ibuprofen or placebo 12- and one-hour prior to running one-hour in a heated chamber (35 °C, 20%-60% R.H.) at an intensity of 60% V̇O2peak. Blood and urine samples were collected pre-, post-, and one-hour post-exercise to assess cytokines and markers of AKI, GI injury, and endotoxemia. One hour of running in the heat increased markers of AKI (urinary product of IGFBP7•TIMP2 [Placebo: ∆ 1.8 ± 0.8 log10(ng/ml)2/1000, Ibuprofen: ∆ 1.8 ± 0.9 log10(ng/ml)2/1000], urinary NGAL, and serum cystatin C), GI damage (I-FABP [Placebo: ∆ 631 ± 446 pg/ml, Ibuprofen: ∆ 576 ± 455 pg/ml]), and inflammatory cytokines (TNFα [Placebo: ∆ 5.2 ± 3.5 pg/ml, Ibuprofen: ∆ 6.2 ± 4.9 pg/ml], IL-6, IL-10, and MCP-1), but these changes were not exacerbated by ibuprofen ingestion. There were effects of time (p < 0.001) and condition (p = 0.03) for serum IL-8, with greater concentrations in the ibuprofen (pre: 11.4 ± 5.1 pg/mL, post: 15.5 ± 7.3 pg/ml) trials than placebo (pre: 9.7 ± 4.2 pg/mL, post: 11.7 ± 5.4 pg/mL). There were no effects of time or condition on markers of endotoxemia (LBP [Placebo: ∆ -1.2 ± 3.2 μg/ml, Ibuprofen: ∆ 1.0 ± 1.6 μg/ml], sCD14). These findings indicate that ibuprofen ingestion does not worsen intestinal or renal injury experienced during one hour of exercise in the heat, but increases pro-inflammatory IL-8.

Early Detection of Severe Acute Kidney Injury by Urinary Neutrophil Gelatinase Associated Lipocalin in Critically Ill Children

Background: Acute Kidney Injury (AKI) is independently associated with worsened morbidity and increased mortality in critically ill children in the Pediatric Intensive Care Unit (PICU). Till date Serum Creatinine (S.Cr) is the gold standard for AKI detection. Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) is revealed as a promising novel biomarker for the early detection of kidney damage. The study is aimed to evaluate the ability of uNGAL for early detection of severe AKI in critically ill children. Materials and methods: This prospective observational study included 90 pediatric ICU (PICU) patients aged 1 month to 12 years from December 2020 to November 2021.Urine was collected for uNGAL on admission (Day 0). Blood samples were collected on Day 0 (D0), Day 3 (D3) and Day 7 (D7) for serum creatinine (S.Cr). AKI was defined and staged according to Kidney Disease Improving Global Outcomes 2012 criteria. Results: Among 90 children, 26 (28.9%) develop severe AKI on D3. The median uNGAL level was 182.9 ng/ml in children with severe AKI compared to 44.3 ng/ml in those without severe AKI. The AUC for the D0 uNGALto predict D3 severe AKI was 0.945 (CI 0.867–1.0). The best cutoff point for uNGAL was 102.70 ng/ml, with a sensitivity of 96.15% and specificity of 98.44% for D3 severe AKI. D0uNGAL had no significant correlation with D0S. Crbut had a significant positive correlation with D3 and D7 S.Cr. Conclusion: Urinary NGAL is an useful early AKI marker to detect the development of severe AKI in critically ill children of PICU. Chatt Maa Shi Hosp Med Coll J; Vol.23 (1); January 2024; Page 29-33

Plasma neutrophil gelatinase-associated lipocalin as a single test rule out biomarker for acute kidney injury: A cross-sectional study in patients admitted to the emergency department.

Acute kidney injury (AKI) is a syndrome with high mortality and morbidity in part due to delayed recognition based on changes in creatinine. A marker for AKI based on a single measurement is needed and therefore the performance of a single measurement of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in patients admitted to the emergency department was tested. Samples from the Triage study which included 6005 consecutive adult patients admitted to the emergency department were tested for pNGAL. The optimal cutoff for pNGAL was determined by the AUC and compared to AKI based on creatinine using different estimations of the premorbid kidney function. In 4833 patients, two or more plasma creatinine (pCr) measurements were available allowing the detection of AKI. The highest prevalence of AKI (10%) was found when defining AKI as an increase in pCr ≥26.5 μmol/L from the prior year's mean pCr. At these conditions the AUC for pNGAL to predict AKI was 85% giving an optimal cutoff of 142.5 ng/mL with a negative predictive value of 0.96, a positive predictive value of 0.35, a specificity of 0.87 and a sensitivity of 0.70. The study illustrates that the value of a single measurement of pNGAL is primarily in excluding AKI whereas it`s poorer in predicting the presence of AKI. When diagnosing AKI with pCr the optimal baseline pCr level is the mean of available pCr (mb-pCr) measurements from up to a year prior to the current event.

The Role of Dapagliflozin in the Modulation of Hypothermia and Renal Injury Caused by Septic Shock in Euglycemic and Hyperglycemic Rat Models.

Recent research has validated the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing glucose levels and exerting a nephroprotective role. This study aimed to examine the impact of dapagliflozin in preventing sepsis-induced acute kidney injury (AKI) and related consequences. The study used both normal and diabetic rat models to investigate whether the effectiveness of dapagliflozin is influenced by glycemia levels. Normal and diabetic Wistar albino rats were treated with dapagliflozin for two weeks and then received a single dose of lipopolysaccharide (LPS). After sepsis induction, skin and deep body temperatures were recorded every two hours. Blood and kidneys were collected for analysis using histological examination and biochemical assays. Dapagliflozin attenuated the consequences of sepsis through mitigation of LPS-induced hypothermia and AKI in the normal and diabetic septic groups. Dapagliflozin regulated the serum levels of AKI markers, including creatinine and blood urea nitrogen, as well as ion levels. Dapagliflozin attenuated LPS-induced AKI through modulation of renal inflammation and oxidative stress, which showed well-abundant glomeruli. These results indicated the protective effect of dapagliflozin against LPS-induced hypothermia and AKI, which was likely unrelated to its glucose-lowering properties, as evidenced in the non-diabetic septic group. The outcomes suggest that dapagliflozin has a potential impact in preventing sepsis-induced hypothermia and AKI via modulation of inflammation and oxidative stress, irrespective of glycemic levels.

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.

Cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy and the value of markers for acute kidney injury

Cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy and the value of markers for acute kidney injury

Prognostic Value of Serum Neutrophil Gelatinase-Associated Lipocalin in Acute Heart Failure: A Meta-Analysis.

Neutrophil gelatinase-associated lipocalin (NGAL) is not only a sensitive marker of acute kidney injury but may also be a prognostic marker of acute heart failure (AHF). This study aimed to investigate the relationship between serum NGAL and all-cause death (ACD) and the composite outcome of ACD or AHF readmissions in patients with AHF. The Embase, Cochrane Library, and PubMed databases were searched for articles focusing on serum NGAL and ACD and the composite outcome of ACD or AHF readmissions in patients with AHF. The hazard ratios (HRs) were pooled with random-effects models. The results from 2428 patients from seven studies were pooled in this article. Higher NGAL was relevant to an increased risk of ACD (HR, 1.89; 95% CI, 1.38 to 2.61) and the composite outcome of ACD or AHF readmissions (HR, 2.92; 95% CI, 1.62 to 5.27) in patients with AHF. Serum NGAL has prognostic value for ACD and the composite outcome of ACD or AHF readmissions in AHF. CRD42022322057, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322057.

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.

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.

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.

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.

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

A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury

ABSTRACT Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801–1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.

Vitamin D deficiency may increase the risk of acute kidney injury in patients with diabetes and predict a poorer outcome in patients with acute kidney injury

BackgoundPeople with diabetes are much more likely to develop acute kidney injury (AKI) than people without diabetes. Low 25-hydroxy-vitamin D [25(OH)D] concentrations increased the risk of AKI in specific populations. Few studies have explored the relationship between the 25(OH)D level and AKI in patients with diabetes. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and the risk of AKI in patients with diabetes, and to evaluate whether the 25(OH)D level could be a good prognostic marker for AKI progression.MethodsA total of 347 patients with diabetes were retrospectively reviewed. The primary endpoint was the first event of AKI. The secondary endpoint is need-of-dialysis. AKI patients were further followed up for 6 months with the composite endpoint of end-stage renal disease (ESRD) or all-cause death. Kaplan–Meier survival analysis and Cox proportional hazards models were used.ResultsDuring a median follow-up of 12 weeks (12.3 ± 6.7), 105 incident AKI were identified. The middle and high tertiles of baseline 25(OH)D levels were associated with a significantly decreased risk of AKI and dialysis compared to the low tertile group (HR = 0.25, 95% CI 0.14–0.46; HR = 0.24, 95% CI 0.13–0.44, respectively, for AKI; HR = 0.15; 95% CI 0.05–0.46; HR = 0.12; 95% CI 0.03–0.42, respectively, for dialysis). Sensitivity analysis revealed similar trends after excluding participants without history of CKD. Furthermore, AKI patients with 25(OH)D deficiency were associated with a higher risk for ESRD or all-cause death (HR, 4.24; 95% CI, 1.80 to 9.97, P < 0.001).ConclusionA low 25 (OH) vitamin D is associated with a higher risk of AKI and dialysis in patients with diabetes. AKI patients with 25(OH)D deficiency were associated with a higher risk for ESRD or all-cause death.

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.

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.

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.

Association of corticosteroid therapy with reduced acute kidney injury and lower NET markers in severe COVID-19: an observational study

BackgroundAcute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19.ResultsTwo hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment.ConclusionCorticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NET markers in plasma.

Complex Pathophysiology of Acute Kidney Injury (AKI) in Aging: Epigenetic Regulation, Matrix Remodeling, and the Healing Effects of H2S.

The kidney is an essential excretory organ that works as a filter of toxins and metabolic by-products of the human body and maintains osmotic pressure throughout life. The kidney undergoes several physiological, morphological, and structural changes with age. As life expectancy in humans increases, cell senescence in renal aging is a growing challenge. Identifying age-related kidney disorders and their cause is one of the contemporary public health challenges. While the structural abnormalities to the extracellular matrix (ECM) occur, in part, due to changes in MMPs, EMMPRIN, and Meprin-A, a variety of epigenetic modifiers, such as DNA methylation, histone alterations, changes in small non-coding RNA, and microRNA (miRNA) expressions are proven to play pivotal roles in renal pathology. An aged kidney is vulnerable to acute injury due to ischemia-reperfusion, toxic medications, altered matrix proteins, systemic hemodynamics, etc., non-coding RNA and miRNAs play an important role in renal homeostasis, and alterations of their expressions can be considered as a good marker for AKI. Other epigenetic changes, such as histone modifications and DNA methylation, are also evident in AKI pathophysiology. The endogenous production of gaseous molecule hydrogen sulfide (H2S) was documented in the early 1980s, but its ameliorative effects, especially on kidney injury, still need further research to understand its molecular mode of action in detail. H2S donors heal fibrotic kidney tissues, attenuate oxidative stress, apoptosis, inflammation, and GFR, and also modulate the renin-angiotensin-aldosterone system (RAAS). In this review, we discuss the complex pathophysiological interplay in AKI and its available treatments along with future perspectives. The basic role of H2S in the kidney has been summarized, and recent references and knowledge gaps are also addressed. Finally, the healing effects of H2S in AKI are described with special emphasis on epigenetic regulation and matrix remodeling.

Urinary chloride excretion in critical illness and acute kidney injury: a paediatric hypothesis-generating cohort study post cardiopulmonary bypass surgery.

Renal chloride metabolism is currently poorly understood but may serve as both a diagnostic and a treatment approach for acute kidney injury. We investigated whether plasma chloride, ammonia and glutamine as well as urinary chloride, ammonium and glutamine concentrations may serve as markers for acute kidney injury in paediatric patients. We conducted a prospective observational trial in a tertiary care paediatric intensive care unit. Ninety-one patients after cardiopulmonary bypass surgery were enrolled. Plasma glutamine, creatinine, (serum) albumin, urinary electrolytes and glutamine were collected pre-cardiopulmonary bypass surgery, at paediatric intensive care unit admission, and at 6, 12, 24, 48 and 72 h after paediatric intensive care unit admission. The urinary strong ion difference was calculated. The median urinary chloride excretion decreased from 51 mmol/L pre-cardiopulmonary bypass to 25 mmol/L at paediatric intensive care unit admission, and increased from 24 h onwards. Patients with acute kidney injury had lower urinary chloride excretion than those without. The median urinary strong ion difference was 59 mmol/L pre-cardiopulmonary bypass, rose to 131 mmol/L at 24 h and fell to 20 mmol/L at 72 h. The plasma chloride rose from 105 mmol/L pre-cardiopulmonary bypass to a maximum of 109 mmol/L at 24 h. At 24 h the plasma chloride concentration was associated with the presence of acute kidney injury. There was no association between plasma or urinary amino acids and chloride excretion or kidney injury. In conclusion, renal chloride excretion decreased in all patients, although this decrease was more pronounced in patients with acute kidney injury. Our findings may reflect a response of the kidneys to critical illness, and acute kidney injury may make these changes more pronounced. Targeting chloride metabolism may offer treatment approaches to acute kidney injury.