Kidney Injury Research Articles

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

BackgroundTacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.Methods and resultsThirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.ConclusionLina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

Diagnosis, management, and outcomes of immune checkpoint inhibitor induced acute interstitial nephritis: A single-center experience.

Immune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (AIN) is a recognized complication of immunotherapy (IO), but literature on its management and outcomes is limited. We retrospectively reviewed patients who received ICIs and developed biopsy-proven or clinically-suspected ICI-associated AIN at the University of Virginia Comprehensive Cancer Center from 2012-2023. We analyzed baseline characteristics and clinical outcomes, including treatment interruption and rechallenge rates. Acute kidney injury (AKI) was defined as a ≥ 1.5-fold increase in baseline creatinine under seven days, a two-fold increase above the upper limit of normal, or an increase by ≥0.3 mg/dL. Kidney function returning to within 0.3 mg/dL or less than twice baseline was considered complete (CRc) and partial (PRc) recovery, respectively. We identified 12 cases of ICI-AIN: four by biopsy (33%) and eight (67%) by clinical suspicion. Two patients received anti-CTLA-4 and anti-PD1, six received anti-PD1 alone, and four received chemo-immunotherapy. The majority (58%) of patients developed AIN within the first 5 cycles. Eight patients developed ≥ Grade 3 AKI, and six developed multiple irAEs. ICI was permanently discontinued in seven patients (58%) and temporarily interrupted in four (30%). The CRc and PRc rates were 67% and 8%, respectively. Upon AIN onset, the best disease response was stable disease in five patients, partial response in three, and progressive disease in three. Median overall survival was 4.87 years, and progression-free survival was 1.5 years. Rechallenge with IO after kidney irAE may be possible in some patients but requires careful evaluation on an individual basis.

Intrarenal pH-Responsive Self-Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury.

Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated β-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10 min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.

Intrarenal pH‐Responsive Self‐Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury

Metabolic acidosis‐induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end‐stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH‐responsive luminescent gold nanoparticles (p‐AuNPs) in the second near‐infrared emission co‐coated with 2,3‐dimethylaleic anhydride conjugated β‐mercaptoethylamine and cationic 2‐diethylaminoethanethiol hydrochloride, which showed sensitive pH‐induced charge reversal and intrarenal self‐assembly for highly sensitive and long‐time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH‐induced intrarenal self‐assembly and enhanced interactions between pH‐triggered positively charged p‐AuNPs and renal tubular cells, the early‐ and late‐stage MAKI could be differentiated rapidly within 10 min post‐injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p‐AuNPs were demonstrated to effectively real‐time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH‐responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early‐stage diagnosis of pH‐related diseases.

Utility of Dexmedetomidine in Paediatric Cardiac Surgery: a Systematic Review and Meta-analysis

Dexmedetomidine is a selector α 2-agonist that provides sedation with sparing respiratory depression, anxiolysis, and analgesic adjunct with opioids and benzodiazepines sparing effects, prolongs the duration of regional anesthesia and allows early tracheal extubation after pediatric cardiac surgery.[1,2,3 ] Recently, dexmedetomidine has been established as a cardioprotective agent in adult cardiac surgical patients. Some trials show significantly lower myocardial injury markers like interleukin-6 (IL-6) levels, cardiac troponin I (cTnI), and creatinine kinase-myocardial band (CK-MB), after cardiac surgery in the dexmedetomidine group.[ ] The majority of published studies have suggested that dexmedetomidine is a seemingly efficacious agent protecting against cardiac injury during CPB.[6] Its administration lowers mechanical ventilation period, ICU stay, and length of hospital stay after pediatric cardiac surgery. In addition, it is effective against postoperative shivering, refractory JET rhythm and Tet spells, and acute kidney injury (AKI) in cyanotic pediatric patients undergoing corrective surgery. However, studies on its application in pediatric heart surgery using cardiopulmonary bypass (CPB) remain limited. This systematic review aimed to provide information on the utility of dexmedetomidine in patients undergoing pediatric cardiac surgery using CPB: hemodynamic stability, cardioprotective, renal protection, neuroprotective effects, control of refractory JET, and Tet spells, and the early and late outcome.

Comparators in Pharmacovigilance: A Quasi-Quantification Bias Analysis.

It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance. We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury. We assessed the directionality of three disproportionality analysis estimates (reporting odds ratio, proportional reporting ratio, information component) using one unrestricted comparator (full data) and two restricted comparators (active comparator, active comparator with class exclusion). Analyses were conducted within two calendar time periods, defined based on external events (approval of direct oral anticoagulants, Food and Drug Administration safety warning on acute kidney injury with sodium-glucose cotransporter 2 inhibitors) hypothesized to alter reporting rates. There were no false-positive signals for rivaroxaban and hepatotoxicity irrespective of the comparator. Restricting to the initial post-approval period led to false-positive signals, with restricted comparators performing worse. There were false-positive signals for canagliflozin and acute kidney injury, with restricted comparators performing better. Restricting to the period before the Food and Drug Administration warning weakened the false-positive signal for canagliflozin and acute kidney injury across comparators. We could not identify a consistent and predictable pattern to the directionality of disproportionality analysis estimates with specific comparators. Calendar time-based restrictions anchored on relevant external events had a considerable impact.

Methyl jasmonate and diphenyl diselenide attenuate diethylnitrosamine and carbon tetrachloride-induced nephrotoxicity in rats via modulation of inflammation and oxidative stress processes

Methyl jasmonate and diphenyl diselenide attenuate diethylnitrosamine and carbon tetrachloride-induced nephrotoxicity in rats via modulation of inflammation and oxidative stress processes

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

The mechanisms of ferroptosis in the pathogenesis of kidney diseases.

The pathological features of acute and chronic kidney diseases are closely associated with cell death in glomeruli and tubules. Ferroptosis is a form of programmed cell death characterized by iron overload-induced oxidative stress. Ferroptosis has recentlygained increasing attention as a pathogenic mechanism of kidney damage. Specifically, the ferroptosis signaling pathway has been found to be involved in the pathological process of acute and chronic kidney injury, potentially contributing to the development of both acute and chronic kidney diseases. This paper aims to elucidate the underlying mechanisms of ferroptosis and its role in the pathogenesis of kidney disease, highlighting its significance and proposing novel directions for its treatment.

Source Tracing of Kidney Injury via the Multispectral Fingerprint Identified by Machine Learning-Driven Surface-Enhanced Raman Spectroscopic Analysis.

Early diagnosis of drug-induced kidney injury (DIKI) is essential for clinical treatment and intervention. However, developing a reliable method to trace kidney injury origins through retrospective studies remains a challenge. In this study, we designed ordered fried-bun-shaped Au nanocone arrays (FBS NCAs) to create microarray chips as a surface-enhanced Raman scattering (SERS) analysis platform. Subsequently, the principal component analysis (PCA)-two-layer nearest neighbor (TLNN) model was constructed to identify and analyze the SERS spectra of exosomes from renal injury induced by cisplatin and gentamycin. The established PCA-TLNN model successfully differentiated the SERS spectra of exosomes from renal injury at different stages and causes, capturing the most significant spectral features for distinguishing these variations. For the SERS spectra of exosomes from renal injury at different induction times, the accuracy of PCA-TLNN reached 97.8% (cisplatin) and 93.3% (gentamicin). For the SERS spectra of exosomes from renal injury caused by different agents, the accuracy of PCA-TLNN reached 100% (7 days) and 96.7% (14 days). This study demonstrates that the combination of label-free exosome SERS and machine learning could serve as an innovative strategy for medical diagnosis and therapeutic intervention.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Experimental animal model. The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

The Preventive Role of Glutamine Supplementation in Cardiac Surgery-Associated Kidney Injury from Experimental Research to Clinical Practice: A Narrative Review

Acute kidney injury represents a significant threat in cardiac surgery regarding complications and costs. Novel preventive approaches are needed, as the therapeutic modalities are still limited. As experimental studies have demonstrated, glutamine, a conditionally essential amino acid, might have a protective role in this setting. Moreover, the levels of glutamine after the cardiopulmonary bypass are significantly lower. In clinical practice, various trials have investigated the effects of glutamine supplementation on cardiac surgery with encouraging results. However, these studies are heterogeneous regarding the selection criteria, timing, dose, outcomes studied, and way of glutamine administration. This narrative review aims to present the potential role of glutamine in cardiac surgery-associated acute kidney injury prevention, starting from the experimental studies and guidelines to the clinical practice and future directions.

Predictive performance of two types of urinary biomarkers for renal non-recovery in sepsis-associated acute kidney injury: a prospective observational study

Background and purposeRenal non-recovery is known to have negative prognostic implications in patients suffering from acute kidney injury (AKI). Nevertheless, the identification of biomarkers for predicting renal non-recovery in sepsis-associated AKI (SA-AKI) within clinical settings remains unresolved. This study aims to evaluate and compare the predictive ability for renal non-recovery, use of kidney replacement therapy (KRT) in the Intensive Care Unit (ICU), and 30-day mortality after SA-AKI by two urinary biomarkers, namely C-C motif chemokine ligand 14 (CCL14) and [TIMP-2]•[IGFBP7].MethodsWe prospectively screened adult patients who met the criteria for AKI stage 2–3 and Sepsis-3.0 in two ICUs from January 2019 to May 2022. Patients who developed new-onset SA-AKI after ICU admission were enrolled and urinary biomarkers including [TIMP-2]•[IGFBP7] and CCL14 were detected at the time of SA-AKI diagnosis. The primary endpoint was non-recovery from SA-AKI within 7 days. The secondary endpoints were the use of KRT in the ICU and 30-day mortality after SA-AKI. The individual discriminative ability of [TIMP-2]•[IGFBP7] and CCL14 to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC).Results141 patients with stage 2–3 SA-AKI were finally included, among whom 54 (38.3%) experienced renal non-recovery. Urinary CCL14 exhibited a higher predictive capability for renal non-recovery compared to [TIMP-2]•[IGFBP7], with CCL14 showing an AUC of 0.901, versus an AUC of 0.730 for [TIMP-2]•[IGFBP7] (P = 0.001). Urinary CCL14 and [TIMP-2]•[IGFBP7] demonstrated a moderate predictive value for the need for KRT in ICU, with AUC values of 0.794 and 0.725, respectively; The AUC of [TIMP-2]•[IGFBP7] combined with CCL14 reached up to 0.816. Urinary CCL14 and [TIMP-2]•[IGFBP7] exhibited poor predictive power for 30-day mortality, with respective AUC values of 0.623 and 0.593.ConclusionUrinary CCL14 had excellent predictive value for renal non-recovery in SA-AKI patients. For predicting the use of KRT in the ICU, the predictive capability of urinary [TIMP-2]•[IGFBP7] or CCL14 was fair. However, a combination of [TIMP-2]•[IGFBP7] and CCL14 showed good predictive ability for the use of KRT.

The efficacy and safety of rituximab with or without glucocorticoid in inducing remission of MCD with different clinical presentations in adults: a retrospective study

Abstract Background To investigate the efficacy and safety of rituximab (RTX) with or without glucocorticoid (GC) in inducing remission of minimal change disease (MCD) in adults. Methods Twenty-one adult MCD patients were included in the study. The patients were assigned to the following three groups according to their background before RTX treatment: an RTX single drug direct induction treatment group (Group A; n = 9), a short-term, low-dose GC combined with RTX induction treatment group (Group B; n = 4) and a short-term, adequate-dose GC-induced remission and RTX maintenance treatment group (Group C; n = 8). The primary endpoints were the time to induction of remission and the rate of clinical remission at 12 months. Results All patients achieved clinical remission, with 19 (90.48%) achieving complete remission (CR), and the median remission time was 4 (2.5, 12) weeks. Eight (88.89%) patients in Group A achieved CR, and the median remission time was 3 (2.25, 14) weeks. In group B, three (75.00%) patients achieved CR, with a median remission time of 4 (4, 10) weeks. In group C, eight (100.00%) patients achieved CR, and the median remission time was 3.5 (2, 4) weeks. Conclusions In MCD patients without acute kidney injury (AKI), adequate RTX alone or short-term combined treatment with low-dose GCs can effectively induce and maintain MCD remission. Adequate short-term GCs combined with RTX maintenance may be an effective alternative for MCD patients in context of AKI. There is a need to investigate different induction therapy regimens for the remission of MCD patients with different backgrounds.

Modified EBP-bFGF targeting endogenous renal extracellular matrix protects against renal ischemia-reperfusion injury in rats.

Acute kidney injury (AKI) is a life-threatening disease primarily caused by renal ischemia-reperfusion (I/R) injury, which can result in renal failure. Currently, growth factor therapy is considered a promising and effective approach for AKI treatment. Basic fibroblast growth factor (bFGF), an angiogenic factor with potent activity, efficiently stimulates angiogenesis and facilitates regeneration of renal tissue. However, the unrestricted diffusion of bFGF restricts its clinical application in AKI treatment. Therefore, developing a novel sustained released system for bFGF could enhance its potential in treating AKI. In this study, we genetically engineered a multifunctional recombinant protein by fusing bFGF with a specific peptide (EBP). EBP-bFGF effectively binds to the extracellular matrix in the injured kidney, enabling slow release of bFGF in AKI. Furthermore, following orthotopic injection into I/R rats' ischemic kidneys, EBP-bFGF exhibited stable retention within the tissue. Additionally, EBP-bFGF suppressed apoptosis of renal cells, reduced renal fibrosis, and facilitated recovery of renal function. These findings suggest that EBP-bFGF delivery system represents a promising strategy for treating AKI.

Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression

IntroductionImmune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.MethodsTwenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.ResultsCisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.ConclusionsOnly mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study

BackgroundPortal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear.Methods110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt—TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC.ResultsThe incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI–II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group.ConclusionCompared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.

The safety of modified, all-oral shorter tuberculosis regimens in Armenia.

The implementation of modified, all-oral shorter regimens for treatment of rifampicin-resistant tuberculosis has started in Armenia since August 2020 under the conditions of operational research. This study aims to evaluate the safety and effectiveness of shorter regimens. We evaluated cumulative incidence rates of serious adverse events, adverse events of grade 3 and greater and events resulting in treatment modifications or suspension for 52 study participants. A new, different pattern of adverse events emerged compared with the previous evaluations of drug safety of treatment for rifampicin-resistant tuberculosis. Arthralgia (23.1%) and peripheral neuropathy (21.2%) took leading positions among the adverse events resulting in modifications of treatment. Some adverse events of interest (prolonged QT interval, elevated liver enzymes and anemia) remained relevant for the patients receiving new combinations of anti-TB drugs. The other adverse events (impaired hearing, acute kidney injury and hypokalemia) lost their significance for safety surveillance of rifampicin-resistant tuberculosis treatment. One unexpected serious adverse event (lymphoproliferative skin lesion) brought to a "failed treatment" outcome. The other serious adverse event was anemia. The shorter regimens proved to be safe and effective for treatment of rifampicin-resistant tuberculosis, but proper follow-up of adverse events is necessary.

Risk factors for acute kidney injury in very-low birth weight newborns: a systematic review with meta-analysis.

This study aims to analyze the main risk factors for acute kidney injury in the subgroup of very-low birth weight newborns, using the diagnosing criteria of the Kidney Disease Improving Global Outcomes (KDIGO) or the Acute Kidney Injury Network (AKIN). A systematic review of the literature was performed on the EMBASE® and PubMed® platforms. Studies that evaluated the risk factors for developing AKI in VLBW newborns were included. For the meta-analysis, we only included the risk factors that were associated with AKI in the univariate analysis of at least two studies. After an initial screening, abstract readings, and full-text readings, 10 articles were included in the systematic review and 9 in the meta-analysis. The incidence of AKI varied from 11.6 to 55.8%. All the studies have performed multivariate analysis, and the risk factors that appeared most were PDA and hemodynamic instability (use of inotropes or hypotension), sepsis, and invasive mechanical ventilation. After the meta-analysis, only cesarian delivery did not show an increased risk of AKI, all the other variables remained as important risk factors. Moreover, in our meta-analysis, we found a pooled increased risk of death in newborns with AKI almost 7 times. Conclusion: AKI in VLBW has several risk factors and must be seen as a multifactorial disease. The most common risk factors were PDA, hemodynamic instability, sepsis, and invasive mechanical ventilation. What is known: • Acute kidney injury is associated with worst outcomes in all ages. It´s prevention can help diminish mortality. What is new: • A synthesis of the main risk factors associated with AKI in very low birth weight newborns.