Search Results (244)

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Background and Aims: Sepsis-associated acute kidney injury (S-AKI) is common and is associated with poor outcomes. This prospective observational study aimed to assess the predictive value of four novel biomarkers—syndecan-1 (SDC1), neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and presepsin (PSPN)—for renal outcomes and mortality in septic ICU patients. Methods: Serum biomarker levels were measured in serum samples collected at the time of sepsis diagnosis on the basis of the Sepsis-3 criteria. Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and patients were grouped by the presence of AKI, renal replacement therapy requirement (RRT), and intensive care unit (ICU) survival. Demographic, clinical, laboratory, and severity score data were compared between groups to evaluate the predictive performance of biomarkers and clinical parameters. Results: Of the 140 septic patients included, 55.0% developed AKI, 17.2% required RRT, and the ICU mortality rate was 50.0%. SDC1 was independently associated with both AKI (OR: 1.201; p = 0.024) and RRT initiation (OR: 1.260; p = 0.004). It also demonstrated the highest predictive performance for RRT (AUC: 0.715; p = 0.001) and a significant AUC for AKI evaluation (AUC: 0.659; p = 0.002). NGAL levels were significantly elevated in patients with AKI and higher SOFA scores but were not independently predictive. PENK and PSPN were not significantly associated with any renal outcome or mortality. The combined SOFA–SDC1 model improved discrimination for both AKI (AUC: 0.770) and RRT (AUC: 0.737), surpassing individual predictors. Conclusions: SDC1 emerged as the most reliable biomarker for assessing AKI and predicting the need for RRT, highlighting its potential role in early renal risk stratification among critically ill patients. Full article

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is associated with significant renal complications, affecting disease progression and patient outcomes. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have emerged as a key therapeutic strategy, offering cardiovascular and renal benefits in these patients. However, interindividual variability in response to dapagliflozin underscores the role of pharmacogenetics in optimizing treatment efficacy. This study investigates the influence of genetic polymorphisms on renal outcomes in HFrEF patients treated with dapagliflozin, focusing on variations in genes such as SLC5A2, UMOD, KCNJ11, and ACE. Methods: This prospective, observational cohort study was conducted at the National Heart Institute, Cairo, Egypt, enrolling 200 patients with HFrEF. Genotyping of selected single nucleotide polymorphisms (SNPs) was performed using TaqMan™ assays. Renal function, including estimated glomerular filtration rate (eGFR), Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels, was assessed at baseline and after six months of dapagliflozin therapy. Results: Significant associations were found between genetic variants and renal outcomes. Patients with AA genotype of rs3813008 (SLC5A2) exhibited the greatest improvement in eGFR (+7.2 mL ± 6.5, p = 0.004) and reductions in KIM-1 (−0.13 pg/mL ± 0.49, p < 0.0001) and NGAL (−6.1 pg/mL ± 15.4, p < 0.0001). Similarly, rs12917707 (UMOD) TT genotypes showed improved renal function. However, rs5219 (KCNJ11) showed no significant impact on renal outcomes. Conclusions: Pharmacogenetic variations influenced renal response to dapagliflozin in HFrEF patients, particularly in SLC5A2 and UMOD genes. These findings highlighted the potential of personalized medicine in optimizing therapy for HFrEF patients with renal complications. Full article

Heartworm disease, caused by Dirofilaria immitis, often leads to pulmonary hypertension (PH), a serious cardiovascular complication in infected dogs. PH may impair renal function through hemodynamic and inflammatory mechanisms, even when traditional biomarkers such as serum creatinine and blood urea nitrogen (BUN) remain within normal ranges. This study aimed to assess urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in dogs naturally infected with D. immitis, with and without PH, to evaluate its potential as an early biomarker of renal dysfunction. Forty-two infected dogs were included and divided into two groups based on the presence (n = 14) or absence (n = 28) of PH, diagnosed via echocardiography. uNGAL concentrations were significantly higher in dogs with PH (mean 66.49 ± 6.67 ng/mL) compared to those without PH (mean 49.01 ± 14.48 ng/mL; p < 0.0001), despite normal creatinine and BUN values. No significant associations were found between uNGAL and sex, age, breed, or clinical signs. These findings suggest that uNGAL may serve as a sensitive biomarker of early renal impairment in dogs with heartworm disease and PH, even in the absence of overt azotemia, supporting its use in clinical evaluation and the monitoring of disease progression. Full article

Exercise training in extreme temperatures concurrent with hypohydration status may potentiate the development of acute kidney injury (AKI) in young, healthy persons. Background/Objectives: It is unknown how repeated training bouts in ambient higher temperatures and humidity may influence measures of AKI. The purpose of this study was to investigate hydration status and renal biomarkers related to AKI in NCAA Division I female soccer athletes during preseason conditioning. Methods: A convenience sample of n = 21 athletes were recruited (mean ± SEM; age: 19.3 ± 0.25 y; height: 169.6 ± 1.36 cm; mass: 68.43 ± 2.46 kg; lean body mass: 45.91 ± 1.13 kg; fat mass: 22.51 ± 1.69 kg; body fat %: 32.22 ± 1.32%). The average temperature was 27.43 ± 0.19 °C, and the humidity was 71.69 ± 1.82%. Body composition, anthropometric, workload, and 14 urine samples were collected throughout the preseason training period for urine specific gravity (USG), creatinine (uCr), cystatin C (uCyst-C), and neutrophil gelatinase-associated lipocalin (uNGAL) analyses. Results: Our investigation showed that, when compared to baseline (D0), the athletes maintained a USG-average euhydrated status (1.019 ± 0.001) and were euhydrated prior to each exhibition game (D5-Pre: p = 0.03; 1.011 ± 0.001; D10-Pre: p = 0.0009; 1.009 ± 0.001); uCr was elevated on D8 (p = 0.001; 6.29 ± 0.44 mg·dL⁻¹·LBM⁻¹) and D10-Post (p = 0.02; 6.61 ± 0.44 mg·dL⁻¹·LBM⁻¹); uCyst-C was elevated on D6 through D10 (p = 0.001; ~0.42 ± 0.01 mg·dL⁻¹); no differences were found in uNGAL concentration. The highest distance (m) displaced was found during exhibition games (D5: p = <0.0001; ~8.6 km and D10: p = <0.0001; ~9.6 km). During the preseason conditioning, the athletes maintained a euhydrated status (~1.019) via USG, an increase in uCr that averaged within a normal range (208 mg·dL⁻¹), and an increase in uCyst-C to near AKI threshold levels (0.42 mg·L⁻¹) for several practice sessions, followed by an adaptive decline. No differences were found in uNGAL, which may be explained by athlete variation, chosen time sample collection, and variation in training and hydration status. Conclusions: The athletes maintained a euhydrated status, and this may help explain why urinary markers did not change or meet the reference threshold for AKI. Full article

Acute kidney injury (AKI) resulting from ischemia/reperfusion (I/R) poses a significant clinical challenge due to its high mortality and complex pathophysiology. Here, the protective actions of Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) in carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced adenosine triphosphate depletion and recovery (ATP-D/R) injury in human kidney-2 (HK2) cells are examined. During ATP-D/R, expression levels of CHCHD2 were significantly reduced. The overexpression of CHCHD2 substantially reduced the levels of ROS, lipid peroxidation, apoptosis, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), whereas the knockdown of CHCHD2 exacerbated cellular injury. Mechanistic studies further demonstrated that overexpression of CHCHD2 restored Nrf2 expression under ATP-D/R conditions, facilitated its nuclear translocation, and upregulated the downstream antioxidant enzyme HO-1. In contrast, the knockdown of Nrf2 reduced the cytoprotective actions of CHCHD2. These findings indicate that CHCHD2 reduces cellular damage by enhancing antioxidant defenses and reducing apoptosis through activating the Nrf2 axis, underscoring its potential as a therapeutic target for AKI. Full article

Although sepsis-induced acute kidney injury (AKI) is associated with significant morbidity and mortality, its treatment remains unresolved. Oxidative stress and inflammation are key elements in the pathomechanism of AKI. Therefore, in the present study, we investigated the role of DJ-1 protein, known for its antioxidant and anti-inflammatory properties in an animal model of lipopolysaccharide (LPS)-induced AKI. The presence of DJ-1 was detected by immunofluorescence staining in mice kidney samples, human embryonic kidney cells (HEK-293), and peripheral blood mononuclear cells (PBMCs). To investigate DJ-1 functions, Compound-23, a specific DJ-1-binding and preserving compound (CAS: 724737-74-0), was used in vitro and in vivo. Compound-23 reduced the H₂O₂-induced reactive oxygen species (ROS) production of the HEK-293 cells, and their LPS- or H₂O₂-induced death, as well. In accordance, Compound-23 decreased the mRNA expression of the oxidative stress markers NAD(P)H quinone dehydrogenase 1 (NQO1) and glutamate-cysteine ligase (GCLC) in the LPS-treated, and NQO1 in the H₂O₂-treated cells. Moreover, Compound-23 reduced the H₂O₂- and LPS-induced mRNA expression of inflammatory cytokine interleukin 6 (IL6) in both HEK-293 and PBMCs. Using the mice model of LPS-induced AKI, we demonstrated that Compound-23 treatment improved the renal functions of the mice. In addition, Compound-23 decreased the renal mRNA expression of kidney injury molecule 1 (Kim1), neutrophil gelatinase-associated lipocalin (Ngal), Nqo1, Gclc, and Il6 in the LPS-treated mice. Our study revealed that compounds protecting DJ-1 functions may protect the kidney from LPS-induced damage, suggesting that DJ-1 could be a potential drug target for sepsis-induced AKI therapy. Full article

Dogs with acute congestive heart failure (CHF) can develop acute kidney injury (AKI); the prevalence of this condition has not been defined. This study aimed to assess the occurrence of AKI (increase in serum creatinine (sCr) ≥ 0.3 mg/dL) within 48 h from admission in dogs with myxomatous mitral valve disease (MMVD) with acute CHF, and the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. This was a multicentric, prospective observational study. Thirty dogs were included. The types and dosages of the diuretics administered, as well as the serum and urinary chemistry, including uNGAL and uNGAL, to the urinary creatinine ratio (uNGALC), were determined at admission (T0) and after 24 (T24) and 48 (T48) hours of hospitalization. Nineteen dogs developed AKI. We found no statistically significant differences in sCr, uNGAL, uNGALC, diuretic dosage, or hours of hospitalization between dogs that developed AKI and those that did not. The urinary NGAL and uNGALC values were not statistically significantly different at any time point, while the sCr was higher at T24 and T48 than T0. Our findings suggest that AKI in MMVD dogs with CHF is primarily functional, driven by effective decongestion rather than severe tubular damage, with the benefits of decongestion outweighing transient increases in sCr. Full article

Objectives: The impact of initial emergency room (ER) factors on survival and renal function in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains unclear. This study aimed to evaluate whether these initial factors influence survival and renal recovery in such patients. Methods: This single-center, retrospective study included 190 critically ill patients admitted to the intensive care unit (ICU) via the ER for CRRT between 1 March 2018, and 31 May 2021. Clinical parameters, including urine output, estimated glomerular filtration rate (eGFR), and serum neutrophil gelatinase-associated lipocalin (NGAL), were assessed. The primary outcomes were 30-day and 90-day mortality, while secondary outcomes included 30-day and 90-day RRT-free durations. Results: Patients with low urine output (LUO, defined as the average of <0.5 mL/kg/h over 6 h) were significantly associated with higher 30-day and 90-day mortality rates. Multivariable Cox regression analysis revealed that the LUO group had an increased risk of 30-day and 90-day mortality (hazard ratios: 1.935 and 2.141, respectively) compared to the high urine output (HUO, defined as the average of ≥0.5 mL/kg/h over 6 h) group. No significant association was observed between mortality and initial eGFR or plasma NGAL levels. However, the HUO group and patients with initial eGFR ≥ 30 mL/min/1.73 m² had longer RRT-free durations at 30 and 90 days. Plasma NGAL levels did not significantly correlate with RRT-free durations. Conclusions: Initial 6-h urine output in the ER is a significant predictor of 30-day and 90-day mortality in critically ill patients undergoing CRRT. Full article

Chronic kidney disease (CKD) remains a significant global health burden, often diagnosed at advanced stages due to the limitations of traditional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR). This review aims to critically evaluate recent advancements in novel biomarkers, multi-omics technologies, and artificial intelligence (AI)-driven diagnostic strategies, specifically addressing existing gaps in early CKD detection and personalized patient management. We specifically explore key advancements in CKD diagnostics, focusing on emerging biomarkers—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), soluble urokinase plasminogen activator receptor (suPAR), and cystatin C—and their clinical applications. Additionally, multi-omics approaches integrating genomics, proteomics, metabolomics, and transcriptomics are reshaping disease classification and prognosis. Artificial intelligence (AI)-driven predictive models further enhance diagnostic accuracy, enabling real-time risk assessment and treatment optimization. Despite these innovations, challenges remain in biomarker standardization, large-scale validation, and integration into clinical practice. Future research should focus on refining multi-biomarker panels, improving assay standardization, and facilitating the clinical adoption of precision-driven diagnostics. By leveraging these advancements, CKD diagnostics can transition toward earlier intervention, individualized therapy, and improved patient outcomes. Full article

Background/Objective: Colistin is the primary treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB) infections, but its use is limited by nephrotoxicity, which reduces its effectiveness. There is an urgent need for nephroprotective agents to address this toxicity. This study investigated the potential of CMP3029, an α-helical peptide, to protect against colistin-induced nephrotoxicity. Methods: In vitro, CMP3029 was applied to HK-2 cells before colistin exposure, and cell viability and reactive oxygen species (ROS) levels were measured. In infected mice, CMP3029 was administered before colistin treatment, and urinary kidney injury molecule-1 (KIM-1), cystatin C levels, neutrophil gelatinase-associated lipocalin (NGAL), and renal damage were assessed. Results: CMP3029 preserved cell viability and significantly reduced mitochondrial ROS in HK-2 cells exposed to colistin. CMP3029 lowered urinary biomarkers and mitigated tubular injury in mice, demonstrating significant nephroprotective effects. Conclusions: These findings suggest that CMP3029 mitigates colistin-induced nephrotoxicity. Given the increasing threat of CR-GNB infections, CMP3029 could be a crucial clinical solution for improving patient outcomes in treating colistin-associated nephrotoxicity. Full article

Background: Major adverse kidney events (MAKEs), including death, persistent AKI (pAKI), and renal replacement therapy, are more common in SARS-CoV-2-related ARDS. Invasive mechanical ventilation (IMV), systemic inflammation, and hemodynamic changes drive this risk. This study examines early IMV settings and urinary kidney biomarkers (UKBs) to better understand the development of MAKEs at 30 days. Methods: This prospective, cross-sectional cohort study was conducted in a single center between September and October 2021. This study included adults (≥18 years) diagnosed with ARDS due to SARS-CoV-2, requiring IMV within the first 6 h of admission. Exclusion criteria included a history of chronic kidney disease (CKD) and pregnant women. Initial mechanical ventilator settings were recorded after compliance-guided PEEP titration, and urine samples were collected for the analysis of UKBs at the same time. Our primary and secondary endpoints were to assess risk factors associated with MAKEs at 30 days and pAKI, respectively. Results: The cohort included 45 patients, with a median age of 57.75 (±18.64) years. In total, 32 (71%) developed MAKEs and 22 (48.8%) developed pAKI. MAKEs were associated with older age (adjusted odds ratio (aORs) = 1.23 95% CI: 1.00–1.22; p = 0.038) and higher driving pressure (ΔP) (aORs = 1.62, 95% CI:1.01–2.60, p = 0.043). Only urinary neutrophil gelatinase-associated lipocalin (uNGal) > 40 ng/mL was associated with pAKI (aORs = 8.54, 95% CI:1.75–41.65, p = 0.008). Conclusions: Early ventilator settings, particularly higher ΔP, play a critical role in the development of MAKEs. uN-Gal could enhance the early detection of pAKI, providing opportunities for timely interventions. Full article

Background/Objectives: Acute kidney injury (AKI) is a significant global health issue with a high morbidity and mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines identify various exposures and susceptibilities as risk factors for AKI. However, the predictive significance of these factors in heterogeneous emergency department (ED) populations remains unclear. We hypothesized that assessing KDIGO-listed exposures and susceptibilities for AKI, alone and in combination, would provide an insight into their predictive value for AKI. Furthermore, we investigated whether adding biomarkers, plasma neutrophil gelatinase-associated lipocalin (pNGAL) and C-reactive protein (CRP), could enhance AKI risk prediction. Methods: Data were analyzed from the prospective longitudinal “NGAL study” conducted at North Zealand University Hospital in Denmark. A total of 344 ED patients were included, with AKI diagnosed using KDIGO’s creatinine-based criteria. Patient data, including medical history, exposures, and susceptibilities, were extracted and analyzed. Predictive performance was evaluated using a receiver operating characteristic (ROC) analysis on individual and combined risk factors. Additional models incorporated pNGAL and CRP to assess their impact on prediction accuracy. Results: Individual exposures and susceptibilities showed a poor predictive performance, with nephrotoxic drugs and advanced age demonstrating the highest sensitivity but a low positive predictive value (PPV). Combining multiple risk factors improved AKI prediction, with models clustering into those optimizing sensitivity or PPV. The inclusion of pNGAL significantly enhanced predictive performance, achieving the highest combined sensitivity and PPV. Although less than pNGAL, CRP also improved prediction, while requiring fewer variables than pNGAL-inclusive models. Conclusions: No individual KDIGO-listed exposure or susceptibility could reliably predict AKI in the ED setting. Combining multiple exposures and susceptibilities improved the predictive accuracy, but the models excelled either at screening or confirmation, not both. The addition of pNGAL and CRP significantly enhanced AKI prediction, emphasizing the need for biomarker integration in risk stratification models. These findings highlight the limitations of clinical parameters alone and underscore the importance of a multifaceted approach to AKI risk assessment. Full article