Establishment and characterization of a novel human malignant melanoma cell line AKI.
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “AKI”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Epidemiological study of hepatitis B virus in children in the Aki area, Kochi-ken, Japan].
Explore the source record for details and available documents.
Adolescent↗
Intra- and extracellular potassium activities and the potassium equilibrium potential in partially depolarized human atrial cells.
Under tissue bath conditions, isolated specimens of human right atrium are characterized by the presence of large numbers of partially depolarized cells. The basis for the depolarization is still not understood. To determine if reduced intracellular potassium activity (aKi) is responsible for the low levels of maximum diastolic potential (MDP), aKi was directly measured with potassium ion-selective micro-electrodes (KISE). The effects of varying bath potassium concentration ([K+]0) on aiK and on the relationship between MDP and the potassium equilibrium potential (EK) also were determined. In 4 mM [K+]0, all specimens studied were partially depolarized (MDP = -43.9 +/- 1.3 mV [mean +/- S.E.]) and beat spontaneously. aKi was 98.1 +/- 1.5 mM, and EK was -93.3 +/- 0.4 mV. Changes in [K+]0 between 2.5 and 40 mM did not change aKi significantly. MDP was relatively insensitive to [K+]0 and was always far positive to EK over the entire range of [K+]0 studied. The ability of the KISE to reliably measure aKi in the face of the spontaneous diastolic depolarization was assessed by using acetylcholine or cooling to depress automaticity. These measures did not significantly alter the calculated aKi. The results indicate that: aKi in human atrial specimens is similar to that in atria from other mammalian species, and the low level of MDP exhibited by human atrial cells subject to conventional tissue bath conditions does not primarily result from low levels of aKi.
Body Fluids↗
Change of intracellular K+ activity in rat soleus muscle during hypokalemia.
The relationship between intracellular total K+ concentration [( K]i) as determined by a flame spectrophotometer and intracellular K+ activity (aKi) as determined by an ion-selective microelectrode was studied in soleus muscle of rats on a diet deficient in K+ for 40 days. [K]i began to fall immediately from the initial stage of hypokalemia, while aKi was well-maintained for 15 days. Then, aKi decreased gradually. The measured resting potential (Em) hyperpolarized beyond the EK was calculated from aKi in hypokalemic rat muscle from day 20 to 40. A rapid increase in aKi occurred over 3 hours in soleus muscle of hypokalemic rats for 5 to 6 weeks. It was concluded that the bound intracellular K+ acts as a buffer for aKi in hypokalemic rat muscle, that Em exceeds EK because the Na+-K+ pump is stimulated by increased [Na]i and that the increase in aKi after denervation is due to the removal of a Na+-K+ pump inhibitor normally released from nerve ending.
Aging↗
Pseudogene-Derived Long Noncoding RNAs GSTM3P1/Gstm2-ps1 Exacerbate Sepsis-Associated Acute Kidney Injury by Suppressing Their Parent Gene Translation.
Long noncoding RNAs are emerging as critical regulators of acute kidney injury (AKI). In this study, the pathologic role of pseudogene-derived long noncoding RNAs GSTM3P1 (human)/Gstm2-ps1 (mouse) in sepsis-associated AKI (SA-AKI) was investigated. Glutathione S-transferase mu 3, pseudogene 1 (GSTM3P1)/glutathione S-transferase mu 2, pseudogene 1 (Gstm2-ps1) were transiently up-regulated in kidney proximal tubular cells at the early stage of SA-AKI in mice treated with lipopolysaccharide (LPS) or cecal ligation and puncture, as well as in LPS-treated proximal tubular cells. Functionally, overexpression of GSTM3P1/Gstm2-ps1 exacerbated LPS-induced proximal tubular cell apoptosis and oxidative stress. In contrast, proximal tubule-specific Gstm2-ps1 knockout mice were significantly protected from LPS-induced AKI, as evidenced by improved renal function and reduced apoptosis, kidney injury markers, and reactive oxygen species. Similarly, these mice showed renal protective effects against cecal ligation and puncture-induced AKI. Mechanistically, overexpression of GSTM3P1/Gstm2-ps1 in proximal tubular cells markedly suppressed parent gene GSTM3/GSTM2 protein but not mRNA expression, indicating a translational repression. Restoration of GSTM3/GSTM2 rescued proximal tubular cells from LPS-induced apoptosis. Furthermore, an RNA pulldown assay revealed that Gstm2-ps1 binds to human antigen R (HuR), a known post-transcriptional regulator for mRNA stability and translation. Overexpression of HuR antagonized Gstm2-ps1-mediated repression of GSTM2, associated with increased cell survival after LPS injury. In conclusion, the early induction of GSTM3P1/Gstm2-ps1 in SA-AKI exacerbates kidney injury by a novel mechanism to sequester HuR and inhibit the translation of parent gene GSTM3/gstm2 for oxidative stress detoxification.
Animals↗
Cellular mechanisms of potassium homeostasis in the mammalian nervous system.
Double-barrelled ion-sensitive microelectrodes were used to measure changes in the intracellular activities of K+, Na+, and Cl- (aKi, aNai, aCli) in neurones of rat sympathetic ganglia and in glial cells of slices from guinea-pig olfactory cortex. In sympathetic neurones, carbachol and gamma-aminobutyric acid (GABA) produced a reversible decrease of aKi. The decrease of aKi during carbachol was accompanied by a rise of aNai, whereas in the presence of GABA decreases of aKi and aCli were seen. The reuptake of K+ released during the action of carbachol was completely blocked by ouabain, whereas furosemide inhibited the aKi recovery after the action of GABA. In glial cells, in contrast to the observations in the sympathetic neurones, aKi and aCli increased, whereas aNai decreased when neuronal activity was enhanced by repetitive stimulation of the lateral olfactory tract. It was found that barium ions and ouabain strongly reduced the activity-related rise of intraglial aKi in slices of guinea-pig olfactory cortex. These data show that mammalian neurones as well as glial cells possess several K+ uptake mechanisms that contribute to potassium homeostasis. Ouabain, furosemide, and Ba2+ are useful pharmacological tools to separate these mechanisms.
Animals↗
Potassium activity and plasma membrane potentials in epithelial cells of toad bladder.
Intracellular potassium activity (aki), mucosal and serosal membrane potential (mEm, sEm), short-circuit current (Isc), and transepithelial potential difference in the epithelium of the toad bladder were measured with a potassium-sensitive liquid ion exchanger and an ordinary microelectrode. Under basal conditions, aki was 41.2 +/- 0.5 mM, corresponding to 54.4 mM in free potassium concentration, so half or more of the intracellular potassium may be of bound form or sequestrated within subcellular organelles. The sEm cannot be explained by only the potassium equilibrium potential (Eeq), because the sEm was markedly lower than the Eeq and no relation was found between them. Ouabain and rotenone decreased the aki, but ethacrynic acid, which also inhibited the Isc and the membrane potentials, did not show any effect on aki. Vasopressin decreased aki with an elevation in mEm, whereas prostaglandin E1 increased the aki with elevation in the sEm. These characteristic changes may afford an insight into the mechanisms by which transcellular electrolyte transport occurs.
Animals↗
Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.
BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.
Humans↗
Diagnostic and prognostic value of fibroblast growth factor 23 in acute kidney injury: systematic review and meta-analysis.
Background: Acute kidney injury (AKI) is associated with high mortality and adverse outcomes. Fibroblast growth factor 23 (FGF23) has emerged as a potential biomarker for AKI; however, its diagnostic and prognostic utility remains inconsistent.Methods: We conducted a systematic review and meta-analysis of studies evaluating circulating intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23) (PROSPERO: CRD42022302659). PubMed, EMBASE, CNKI, and Wanfang databases were searched through June 9, 2026. QUADAS-2 was used for quality assessment. A random-effects bivariate model pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC AUC).Results: Twenty-three studies were included: 17 diagnostic, 6 prognostic (one addressing both). For AKI diagnosis, the pooled sensitivity was 0.79 (95% CI 0.73-0.86), specificity 0.82 (95% CI 0.75-0.89), PLR 4.40 (95% CI 2.59-6.21), NLR 0.25 (95% CI 0.16-0.34), DOR 17.49 (95% CI 8.67-35.16), and SROC AUC 0.87 (95% CI 0.81-0.92). Substantial heterogeneity was observed (I2 = 67%), with iFGF23 demonstrating higher accuracy than cFGF23 (AUC 0.91 vs 0.81). For AKI mortality, pooled sensitivity was 0.77 (95% CI 0.69-0.84), specificity 0.76 (95% CI 0.70-0.82), DOR 10.89 (95% CI 6.86-17.30), and SROC AUC 0.77 (95% CI 0.70-0.83). Significant heterogeneity was noted (I2 = 86.2% for sensitivity, 80.4% for specificity). No significant publication bias was detected.Conclusions: Circulating FGF23 exhibits moderate-to-high diagnostic and moderate prognostic performance in AKI, though interpretation is limited by substantial heterogeneity. It may serve as a complementary biomarker for risk stratification, pending further validation with standardized protocols.
Humans↗
Intracellular potassium activities in Amphiuma small intestine.
Intracellular potassium activity (aKi) has been determined in absorptive cells lining the villi of isolated, stripped proximal segments of Amphiuma small intestine. With single-barreled liquid ion-exchanger microelectrodes aKi = 41.6 +/- 1.5 mM in normal chloride buffer; with double-barreled microelectrodes constructed by a new method aKi = 38.5 +/- 2.4 mM. Also, by the latter approach aKi = 41.1 +/- 2.1 mM in buffer in which potassium was elevated to 5 meq/liter and aKi = 44.2 +/- 1.3 mM in sulfate buffer with the same bath potassium concentration. Since the calculated potassium equilibrium potential exceeds the membrane potential this ion is accumulated by the intestinal absorptive cell. A major portion of cellular potassium is bound or compartmentalized since the intracellular potassium activity coefficient is very low. A layer exists near the villi in which the potassium activity exceeds that in the bath buffer solution.
Amphibians↗
Effects of hyperosmotic medium on hepatocyte volume, transmembrane potential and intracellular K+ activity.
Hepatocyte transmembrane potential (Vm) behaves as an osmometer and varies with changes in extracellular osmotic pressure created by altering the NaCl concentration in the external medium (Howard, L.D. and Wondergem, R. (1987) J. Membr. Biol. 100, 53). We now have demonstrated similar effects on Vm by increasing external osmolality with added sucrose and not altering ionic strength. We also have demonstrated that hyperosmotic stress-induced depolarization of Vm results from changes in membrane K+ conductance, gK, rather than from changes in the K+ equilibrium potential. Vm and aKi of hepatocytes in liver slices were measured by conventional and ion-sensitive microelectrodes, respectively. Cell water vols. were estimated by differences in wet and dry weights of liver slices after 10-min incubations. Effect of hyperosmotic medium on membrane transference number for K+, tK, was measured by effects on Vm of step-changes in external [K+]. Hepatocyte Vm decreased 34, 52 and 54% when tissue was superfused with medium made hyperosmotic with added sucrose (50, 100 and 150 mM). Correspondingly, aKi increased 10, 18 and 29% with this hyperosmotic stress of added sucrose. Tissue water of 2.92 +/- 0.10 kg H2O/kg dry weight in control solution decreased to 2.60 +/- 0.05, 2.25 +/- 0.06 and 2.22 +/- 0.05 kg H2O/kg dry weight with additions to medium of 50, 100 and 150 mM sucrose, respectively. Adding 50 mM sucrose to medium decreased tK from 0.20 +/- 0.01 to 0.05 +/- 0.01. Depolarization by 50% with hyperosmotic stress (100 mM sucrose) also occurred in Cl-free medium where Cl- was substituted with gluconate. We conclude that hepatocytes shrink during hyperosmotic stress, and the aKi increases. The accompanying decrease in Vm is opposite to that expected by an increase in aKi, and at least in part results from a concomitant decrease in gK. Changes in membrane Cl- conductance most likely do not contribute to osmotic stress-induced depolarization, since equivalent decreases in Vm occurred with added sucrose in cells depleted of Cl- by superfusing tissue with Cl-free medium.
Animals↗
Effect of ureteral obstruction on proximal tubular functions of rat kidney.
The effect of complete unilateral ureteral obstruction (CUUO) on proximal tubular functions was studied in rats, using the K+-sensitive microelectrode technique and split oil drop method. In the control kidneys peritubular membrane potential (EMperi) and intracellular potassium activity (aKi) were -70.8 +/- 7.0 mV and 81.2 +/- 22.0 mEq/liter (mean +/- SD), respectively. In the CUUO kidneys both EMperi and aKi were progressively reduced with the duration of obstruction. However, in all tubules aKi values were still above the electrochemical equilibrium. In the three days' CUUO kidneys EMperi and aKi were -51.5 +/- 11.7 mV and 53.8 +/- 22.8 mEq/liter, respectively. Rate of fluid absorption (JVL;nl./sec. mm.) across the proximal tubular epithelium from Ringer solution in the control and three days' CUUO kidneys was 0.029 and 0.0065 respectively. In the CUUO kidneys there were wide variations in JVL and EMperi, but there was a clear correlation between these two variables. JVL from choline chloride solution was negligible in both control and CUUO kidneys. From above results, it was suggested that the proximal tubular reabsorption primarily depending on the Na+-K+ pump might be reduced but still working in the CUUO kidney, and thus the proximal tubular reabsorption might take part in preservation of glomerular filtration during the obstruction.
Animals↗
Intracellular Na+ and K+ activities and membrane conductances in the collecting tubule of Amphiuma.
Membrane potentials and conductances, and intracellular ionic activities were studied in isolated perfused collecting tubules of K+-adapted Amphiuma. Intracellular Na+ (aNai) and K+ (aKi) activities were measured, using liquid ion-exchanger double-barreled microelectrodes. Apical and basolateral membrane conductances were estimated by cable analysis. The effects of inhibition of the apical conductance by amiloride (10(-5) M) and of inhibition of the basolateral Na-K pump by either a low K+ (0.1 mM) bath or by ouabain (10(-4) M) were studied. Under control conditions, aNai was 8.4 +/- 1.9 mM and aKi 56 +/- 3 mM. With luminal amiloride, aNai decreased to 2.2 +/- 0.4 mM and aKi increased to 66 +/- 3 mM. Ouabain produced an increase of aNai to 44 +/- 4 mM, and a decrease of aKi to 22 +/- 6, and similar changes were observed when the tubule was exposed to a low K+ bath solution. During pump inhibition, there was a progressive decrease of the K+-selective basolateral membrane conductance and of the Na+ permeability of the apical membrane. A similar inhibition of both membrane conductances was observed after pump inhibition by low K+ solution. Upon reintroduction of K+, a basolateral membrane hyperpolarization of -23 +/- 4 mV was observed, indicating an immediate reactivation of the electrogenic Na-K pump. However, the recovery of the membrane conductances occurred over a slower time course. These data imply that both membrane conductances are regulated according to the intracellular ionic composition, but that the basolateral K+ conductance is not directly linked to the pump activity.
Animals↗
Intracellular potassium and membrane potential in rat muscles during malnutrition and subsequent refeeding.
Nutrition alters total body potassium (TBK) and muscle potassium but little is known about in vivo intracellular K+. We measured free intracellular potassium-ion activity (aKi+), membrane potential (Em), and total potassium (Kt) and calculated intracellular potassium concentration [K+]i in predominantly slow- (soleus) and fast- (extensor digitorum longus) twitch muscles in rats undergoing underfeeding and subsequent refeeding. After underfeeding, aKi+ and Em decreased (P less than 0.025 and P less than 0.006, respectively) only in soleus muscle with restoration after refeeding, whereas [K+]i decreased in both muscles (P less than 0.005) and remained low after refeeding. K+ supplementation did not significantly change these indices or the ratio of free to total intracellular potassium (gamma Ki+). The data show that aKi+ behaves differently from [K+]i during malnutrition and that changes in aKi+ occur especially in slow-twitch fibers, suggesting that previously observed changes in TBK and muscle function are the result of fundamental alterations in muscle-cell energetics and membrane functions, not just mass.
Animals↗
Clinical outcomes and care for spontaneous bacterial peritonitis: A national cohort study.
BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) leads to high rates of acute kidney injury (AKI), hepatorenal syndrome, and mortality. Population-based studies on contemporary SBP epidemiology are needed to inform care. In a large, national cohort of patients diagnosed with SBP and confirmed by ascitic fluid criteria, we characterized ascitic fluid characteristics, in-hospital and 12-month mortality, AKI, and recurrent SBP. APPROACH AND RESULTS: We investigated how individual and bundled quality measures for SBP associated with outcomes after multi-level adjustment for health-system, patient clinical factors, and quality measures. Individual and bundled quality metrics were inpatient antibiotics within 48 hours, i.v. albumin, repeat paracentesis within 48 hours, recognition of SBP, and prophylactic antibiotics upon discharge. Among 4330 patients with newly diagnosed SBP, in-hospital mortality was 15.5%, and 12-month mortality was 56.6%. The incidence of stage 1 AKI was 26.6%, 15.7% for stage 2, and 22.8% for stage 3. The cumulative incidence of recurrent SBP was 10.3%. Guideline-recommended albumin was the only individual metric associated with reduced in-hospital mortality (HR: 0.73, 95% CI: 0.59-0.91). Receipt of a higher number of metrics from the SBP bundle was associated with progressively lower 12-month post-discharge mortality: patients who received 3, 4, and 5 SBP bundle components had 20%, 38%, and 56% lower hazard of mortality, respectively, relative to those receiving 2 or fewer (all p <0.001). The SBP bundle was associated with a lower incidence of stage 3 versus stage 0-2 AKI (OR: 0.66, 95% CI: 0.51-0.86). CONCLUSIONS: Prospective implementation of evidence-based SBP bundles may improve care outcomes and mortality in SBP.
Humans↗
Liquid Biopsy-Multiomics Link Adhesion Pathway Dysregulation to Kidney Injury Severity.
INTRODUCTION: Severe acute kidney injury (AKI) is strongly associated with the risk of developing chronic kidney disease; however, little is known about the cell type-specific mechanisms driving kidney injury severity. METHODS: In this multicenter observational study, we used clinically obtained liquid biopsy proteomics and machine learning (ML) to predict severe outcomes in patients with COVID-associated and non-COVID AKI. Further, we orthogonally combined 169 urine proteomics with 437 plasma proteomics samples and 40 urine sediment single-cell transcriptomics samples to identify complementary dysregulated mechanisms. RESULTS: Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrate predictive power for both discovery and validation set with AUC of 87% and 76%, respectively. These predictive proteomics features obtained demonstrate that cell adhesion and autophagy-associated pathways are uniquely impacted in severe AKI. Differentially abundant proteins (DAPSs) associated with these pathways are highly expressed in cells of the juxtamedullary nephron, endothelial cells (ECs), and podocytes, indicating that these kidney cell types could be potential targets. Single-cell transcriptomic analysis in the in vitro model of kidney organoids infected with SARS-CoV-2 reveal dysregulation of extracellular matrix (ECM) organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters shows significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. CONCLUSION: Collectively, these data suggest that ECM degradation and adhesion-associated mechanisms could be the main driver of severe kidney injury.
AKI↗
Antibodies directed against a yeast carboxyl-terminal peroxisomal targeting signal specifically recognize peroxisomal proteins from various yeasts.
The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme (hydratase-dehydrogenase-epimerase) to peroxisomes of both Candida albicans and Saccharomyces cerevisiae (Aitchison,J.D., Murray, W.W. and Rachubinski, R. A. (1991).J. Biol. Chem. 266, 23197-23203). We investigated the possibility that this tripeptide may act as a general peroxisomal targeting signal (PTS) for other proteins in the yeasts C. tropicalis, C. albicans, Yarrowia lipolytica and S. cerevisiae, and in rat liver. Anti-AKI antibodies raised against the carboxyl-terminal 12 amino acids of trifunctional enzyme were used to search for this PTS in proteins of these yeasts and of rat liver. The anti-AKI antibodies reacted exclusively with multiple peroxisomal proteins from the yeasts C. tropicalis, C. albicans and Y. lipolytica. There was a weak reaction of the antibodies with one peroxisomal protein from S. cerevisiae and no reaction with peroxisomal proteins from rat liver. Antibodies directed against a synthetic peptide containing a carboxyl-terminal Ser-Lys-Leu PTS (Gould, S. J., Krisans, S., Keller, G.-A. and Subramani, S. (1990). J. Cell Biol. 110,27-34) reacted with multiple peroxisomal proteins of rat liver and with peroxisomal proteins of yeast distinct from those identified with anti-AKI antibodies. These results provide evidence that several peroxisomal proteins of different yeasts contain a PTS antigenically similar to that of C. tropicalis trifunctional enzyme and that this signal is absent from peroxisomal proteins from at least one mammalian system, rat liver.
Amino Acid Sequence↗
Multiple oestradiol functions inhibit ferroptosis and acute kidney injury.
Acute tubular necrosis mediates acute kidney injury (AKI) and nephron loss1, the hallmark of end-stage renal disease2-4. For decades, it has been known that female kidneys are less sensitive to AKI5,6. Acute tubular necrosis involves dynamic cell death propagation by ferroptosis along the tubular compartment7,8. Here we demonstrate abrogated ferroptotic cell death propagation in female kidney tubules. 17β-oestradiol establishes an anti-ferroptotic state through non-genomic and genomic mechanisms. These include the potent direct inhibition of ferroptosis by hydroxyoestradiol derivatives, which function as radical trapping antioxidants, are present at high concentrations in kidney tubules and, when exogenously applied, protect male mice from AKI. In cells, the oxidized hydroxyoestradiols are recycled by FSP19,10, but FSP1-deficient female mice were not sensitive to AKI. At the genomic level, female ESR1-deficient kidney tubules partially lose their anti-ferroptotic capacity, similar to ovariectomized mice. While ESR1 promotes the anti-ferroptotic hydropersulfide system, male tubules express pro-ferroptotic proteins of the ether lipid pathway which are suppressed by ESR1 in female tissues until menopause. In summary, we identified non-genomic and genomic mechanisms that collectively explain ferroptosis resistance in female tubules and may function as therapeutic targets for male and postmenopausal female individuals.
Ferroptosis↗