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1.
Saudi Med J ; 45(5): 510-517, 2024 May.
Article in English | MEDLINE | ID: mdl-38734436

ABSTRACT

OBJECTIVES: To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS: Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS: Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION: This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.


Subject(s)
Acute Kidney Injury , Rhabdomyolysis , Tertiary Care Centers , Humans , Rhabdomyolysis/epidemiology , Rhabdomyolysis/etiology , Rhabdomyolysis/complications , Rhabdomyolysis/therapy , Male , Female , Adult , Middle Aged , Saudi Arabia/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/mortality , Retrospective Studies , Liver Failure, Acute/mortality , Liver Failure, Acute/epidemiology , Liver Failure, Acute/therapy , Liver Failure, Acute/etiology , Liver Failure, Acute/complications , Intensive Care Units , Renal Dialysis , Multiple Organ Failure/etiology , Multiple Organ Failure/epidemiology , Multiple Organ Failure/mortality , Fatigue/etiology , Young Adult
2.
Function (Oxf) ; 5(3): zqae012, 2024.
Article in English | MEDLINE | ID: mdl-38706963

ABSTRACT

Acute kidney injury (AKI) is a heterogeneous syndrome, comprising diverse etiologies of kidney insults that result in high mortality and morbidity if not well managed. Although great efforts have been made to investigate underlying pathogenic mechanisms of AKI, there are limited therapeutic strategies available. Extracellular vesicles (EV) are membrane-bound vesicles secreted by various cell types, which can serve as cell-free therapy through transfer of bioactive molecules. In this review, we first overview the AKI syndrome and EV biology, with a particular focus on the technical aspects and therapeutic application of cell culture-derived EVs. Second, we illustrate how multi-omic approaches to EV miRNA, protein, and genomic cargo analysis can yield new insights into their mechanisms of action and address unresolved questions in the field. We then summarize major experimental evidence regarding the therapeutic potential of EVs in AKI, which we subdivide into stem cell and non-stem cell-derived EVs. Finally, we highlight the challenges and opportunities related to the clinical translation of animal studies into human patients.


Subject(s)
Acute Kidney Injury , Extracellular Vesicles , Acute Kidney Injury/therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Humans , Extracellular Vesicles/transplantation , Extracellular Vesicles/metabolism , Animals , Cell Culture Techniques/methods , MicroRNAs/metabolism , MicroRNAs/genetics
3.
Crit Care Explor ; 6(5): e1084, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38709083

ABSTRACT

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Critical Illness , Multiple Organ Failure , Humans , Female , Male , Multiple Organ Failure/therapy , Multiple Organ Failure/etiology , Multiple Organ Failure/physiopathology , Critical Illness/therapy , Retrospective Studies , Child , Continuous Renal Replacement Therapy/methods , Adolescent , Acute Kidney Injury/therapy , Acute Kidney Injury/physiopathology , Child, Preschool , Young Adult , Infant , Organ Dysfunction Scores , Cohort Studies , Adult , Renal Replacement Therapy/methods
4.
Arch Esp Urol ; 77(3): 263-269, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38715167

ABSTRACT

OBJECT: This study aimed to analyse the risk factors and prognosis of sepsis complicated with acute kidney injury (AKI). METHODS: The clinical data of 324 patients with sepsis in the nephrology department of our hospital from January 2022 to January 2023 were collected. A total of 188 patients with AKI were the occurrence group, and 136 patients without AKI were the non-occurrence group. The influencing factors and prognosis of sepsis complicated with AKI were analysed. RESULTS: We observed significant differences in Acute Physiology and Chronic Health Evaluation II (APACHE II), total length of hospital stay, Intensive Care Unit (ICU) stay, mechanical ventilation support, diabetes mellitus and urine volume >1500 mL between the two groups (p < 0.05). After a follow-up period of 1 month, 125 (66.49%) of 188 patients with sepsis complicated with AKI died, and 63 (33.51%) survived. The results of logistic regression analysis showed that Sequential Organ Failure Assessment (SOFA), APACHE II, mechanical ventilation support, diabetes, urine volume >1500 mL and serum creatinine were independent risk factors of sepsis complicated with AKI (p < 0.05). Moreover, SOFA, APACHE II, ICU admission days, mechanical ventilation support, serum creatinine and non-continuous renal replacement therapy were independent risk factors of death in patients with sepsis complicated with AKI (p < 0.05). CONCLUSIONS: SOFA, APACHE II, ICU admission days, mechanical ventilation support, serum creatinine and non-continuous renal replacement therapy may be the influencing factors leading to death in patients with sepsis complicated with AKI. Early clinical intervention should be performed.


Subject(s)
Acute Kidney Injury , Sepsis , Humans , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/complications , Sepsis/complications , Male , Female , Risk Factors , Prognosis , Middle Aged , Aged , Hospitalization , Retrospective Studies
5.
Nefrologia (Engl Ed) ; 44(2): 119-128, 2024.
Article in English | MEDLINE | ID: mdl-38697693

ABSTRACT

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.


Subject(s)
Acute Kidney Injury , Gastrointestinal Microbiome , Sepsis , Humans , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Gastrointestinal Microbiome/physiology , Sepsis/complications , Anti-Bacterial Agents/therapeutic use , Probiotics/therapeutic use , Fluid Therapy/methods
6.
Ann Saudi Med ; 44(2): 104-110, 2024.
Article in English | MEDLINE | ID: mdl-38615183

ABSTRACT

BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. OBJECTIVE: Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. DESIGN: Retrospective cohort. SETTING: Intensive care unit. PATIENTS AND METHODS: We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. RESULTS: Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. CONCLUSION: Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. LIMITATIONS: Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.


Subject(s)
Acute Kidney Injury , Community-Acquired Infections , Pneumonia , Humans , Female , Prevalence , Respiration, Artificial , Retrospective Studies , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Pneumonia/epidemiology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/therapy
7.
Int J Mol Sci ; 25(7)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38612680

ABSTRACT

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.


Subject(s)
Acute Kidney Injury , Hyperbaric Oxygenation , Reperfusion Injury , Animals , Rats , Antioxidants , NF-kappa B , Rats, Inbred SHR , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Kidney , Ischemia , Reperfusion , Oxidative Stress , Oxygen , DNA Damage , Biomarkers , DNA
8.
JAAPA ; 37(5): 22-27, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38595172

ABSTRACT

ABSTRACT: Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.


Subject(s)
Acetaminophen , Liver Failure, Acute , Liver Transplantation , Humans , Liver Failure, Acute/therapy , Liver Failure, Acute/chemically induced , Liver Failure, Acute/diagnosis , Acetaminophen/adverse effects , Drug Overdose/therapy , Brain Edema/etiology , Brain Edema/therapy , Analgesics, Non-Narcotic/adverse effects , Acute Kidney Injury/therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Antidotes
9.
Life Sci ; 346: 122628, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38614303

ABSTRACT

Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.


Subject(s)
Acute Kidney Injury , Exercise , Renal Insufficiency, Chronic , Humans , Animals , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/metabolism , Exercise/physiology , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Oxidative Stress , Antioxidants/metabolism , Autophagy/physiology , Exercise Therapy/methods , Apoptosis
10.
Stem Cell Res Ther ; 15(1): 119, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38659070

ABSTRACT

BACKGROUND: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. METHODS: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. RESULTS: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. CONCLUSIONS: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.


Subject(s)
Acute Kidney Injury , Inflammation , Acute Kidney Injury/therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Rats , Humans , Inflammation/pathology , Inflammation/metabolism , Male , Secretome/metabolism , Adipose Tissue/cytology , Adipose Tissue/metabolism , Rats, Sprague-Dawley , Injections, Subcutaneous , Kidney/metabolism , Kidney/pathology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Reperfusion Injury/metabolism , Reperfusion Injury/therapy , Stromal Cells/metabolism
11.
ScientificWorldJournal ; 2024: 8897932, 2024.
Article in English | MEDLINE | ID: mdl-38623388

ABSTRACT

Background: Acute kidney injury (AKI) is a major medical problem affecting patients' quality of life and healthcare costs. Objectives: This study evaluated the severity, risk factors, and outcomes of patients diagnosed with acute kidney injury (AKI), including community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), who were admitted to tertiary institutions in Palestine. Methods: This retrospective cross-sectional study was conducted at multiple tertiary care hospitals in Palestine by reviewing patient charts from January 2020 to March 2023. The study included all patients aged ≥18 years who were admitted to the hospital and diagnosed with AKI at admission (CA-AKI) or who developed AKI 48 hours after admission (HA-AKI). Patients with incomplete medical records and those with no reported creatinine levels during their stay, pregnant women, kidney transplant patients, and end-stage renal disease patients were excluded. Data were analyzed using SPSS v22.0. The incidence of AKI in each group was compared using the chi-squared test. Results: This study included 259 participants. HA-AKI was present in 27.3% of the patients, while CA-AKI was 72.7%. The most common stage among patients was stage 3 (55.7%, HA-AKI) (42.9%, CA-AKI), and the most common comorbidity contributing to AKI was CKD. NSAIDs, ACE-I/ARBs, and DIURETICs were the most nephrotoxic drugs contributing to AKI. Patients with hyperphosphatemia, hyperkalemia, severe metabolic acidosis, or stage 3 AKI require renal replacement therapy. In addition, our findings revealed a significant association among AKI mortality, age, and heart disease. Conclusion: CA-AKI was more prevalent than HA-AKI in Palestinian patients admitted for AKI. Risk factors for AKI included diabetes, CKD, and medications (antibiotics, NSAID, diuretics, and ACE-I/ARB). Preventive measures, medication management, and disease state management are necessary to minimize AKI during hospital admission or in the community.


Subject(s)
Acute Kidney Injury , Kidney Failure, Chronic , Pregnancy , Humans , Female , Adolescent , Adult , Cross-Sectional Studies , Angiotensin Receptor Antagonists , Retrospective Studies , Arabs , Quality of Life , Angiotensin-Converting Enzyme Inhibitors , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Risk Factors , Diuretics
13.
Stem Cell Res Ther ; 15(1): 105, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600585

ABSTRACT

BACKGROUND: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform. METHODS: hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT. RESULTS: hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24-48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control. CONCLUSIONS: The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology.


Subject(s)
Acute Kidney Injury , Exosomes , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Mesenchymal Stem Cells/physiology , Acute Kidney Injury/therapy , Hypoxia , Lab-On-A-Chip Devices
14.
Toxicon ; 242: 107704, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38565396

ABSTRACT

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.


Subject(s)
Antivenins , Crotalid Venoms , Crotalinae , Poison Control Centers , Snake Bites , Snake Bites/therapy , India , Animals , Humans , Antivenins/therapeutic use , Male , Acute Kidney Injury/therapy , Adult , Female , Middle Aged
15.
Ren Fail ; 46(1): 2345747, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38666354

ABSTRACT

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.


Subject(s)
Acute Kidney Injury , Biomarkers , Delphi Technique , Renal Replacement Therapy , Acute Kidney Injury/urine , Acute Kidney Injury/therapy , Acute Kidney Injury/diagnosis , Humans , Biomarkers/urine , Consensus , Chemokines, CC/urine , Europe
16.
Adv Kidney Dis Health ; 31(2): 133-138, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38649217

ABSTRACT

Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population experiences several characteristic types of acute kidney injury: hypovolemic-mediated (prerenal), ischemic/nephrotoxic-mediated (acute-tubular necrosis), and hepatorenal syndrome. Prerenal acute kidney injury is treated with volume resuscitation. Acute-tubular necrosis is treated by optimizing perfusion pressure and discontinuing the offending agent. Hepatorenal syndrome, a unique physiology of decreased effective arterial circulation leading to renal vasoconstriction and ultimately acute kidney injury, is treated with plasma expansion with albumin and splanchnic vasoconstrictors such as terlipressin or norepinephrine. Common acute stressors such as bleeding, infection, and volume depletion often contribute to multifactorial acute kidney injury. Even with optimal medical management, many clinicians are faced with the challenge of initiating renal replacement therapy in these patients. This article reviews the epidemiology, indications, and complex considerations of renal replacement therapy for acute kidney injury in decompensated cirrhosis.


Subject(s)
Acute Kidney Injury , Hepatorenal Syndrome , Liver Cirrhosis , Renal Replacement Therapy , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/therapy , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Renal Replacement Therapy/methods , Hepatorenal Syndrome/therapy , Hepatorenal Syndrome/etiology , Hepatorenal Syndrome/physiopathology
17.
Adv Kidney Dis Health ; 31(2): 100-110, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38649214

ABSTRACT

Hepatorenal syndrome (HRS) is a feared complication in patients with advanced cirrhosis and is associated with significant morbidity and mortality. While recognized as a distinct physiologic condition for well over one hundred years, a lack of objective diagnostic tests has made the diagnosis one of exclusion. Since 1979, multiple sets of diagnostic criteria have been proposed. Though varying in detail, the principal intent of these criteria is to identify patients with severe, functional acute kidney injury that is unresponsive to volume resuscitation and exclude those with structural injury. However, accurate differential diagnosis remains challenging. Recently, multiple urinary biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin, have been studied as a means of objectively phenotyping etiologies of acute kidney injury in patients with cirrhosis. Along with markers reflecting tubular functional integrity, including the fractional excretion of sodium, injury markers will likely be incorporated into future diagnostic criteria. Making an accurate diagnosis is critical, as therapeutic options exist for HRS but must be given in a timely manner and only to those patients likely to benefit. Terlipressin, an analog of vasopressin, is the first line of therapy for HRS in much of the world and has recently been approved for use in the United States. Significant questions remain regarding the optimal dosing strategy, metrics for titration, and the potential role of point-of-care ultrasound to help guide concurrent albumin administration.


Subject(s)
Biomarkers , Hepatorenal Syndrome , Terlipressin , Humans , Hepatorenal Syndrome/diagnosis , Hepatorenal Syndrome/therapy , Hepatorenal Syndrome/etiology , Biomarkers/urine , Terlipressin/therapeutic use , Lypressin/analogs & derivatives , Lypressin/therapeutic use , Vasoconstrictor Agents/therapeutic use , Diagnosis, Differential , Lipocalin-2/urine , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy
18.
Ren Fail ; 46(1): 2343810, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38655876

ABSTRACT

OBJECTIVE: This single center retrospective study aimed to describe the variables associated with outpatient dialysis dependence in extracorporeal membrane oxygenation (ECMO) patients who needed continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) during their hospitalization. METHODS: Retrospective study of patients who required ECMO-CRRT. RESULTS: Between the years of 2016 and 2022, 202 patients required ECMO-CRRT. One hundred and six patients (52.5%) survived their hospitalization and were followed up for a median of 391 [133, 1005] days. Eighty-one patients (76.5%) recovered kidney function and were dialysis-free before hospital discharge. Twenty-five patients (23.5%) were hemodialysis-dependent after hospitalization. On multivariate regression analysis, hyperlipidemia (odds ratio, OR 6.08 [1.67-22]) and CRRT duration (OR 1.09 [1.03-1.15]) were associated with the need for dialysis post-hospitalization. In this group, 16 patients eventually became dialysis-free, after a median of 49 [34.7, 78.5] days. These patients had a higher median baseline glomerular filtration rate (GFR) compared to those who never recovered renal function (93 mL/min/1.73 m2 [82.4, 104.3] vs. 63.8 mL/min/1.73 m2 [37.9, 83], p = .009). Their follow-up GFR was lower compared to those who recovered renal function before hospital discharge; (87 mL/min/1.73 m2 [68.2, 98.9] vs. 99 mL/min/1.73 m2 [79, 118], p = .07). CONCLUSIONS: AKI requiring CRRT was associated with high mortality in patients receiving ECMO. Nonetheless, most ECMO survivors became dialysis-free before hospital discharge. Variables associated with the need for outpatient dialysis included hyperlipidemia and prolonged need for CRRT during hospitalization.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Extracorporeal Membrane Oxygenation , Glomerular Filtration Rate , Renal Dialysis , Humans , Male , Female , Retrospective Studies , Middle Aged , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Adult , Aged , Hospitalization/statistics & numerical data , Risk Factors , Patient Discharge , Hyperlipidemias/therapy
19.
BMC Nephrol ; 25(1): 122, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580977

ABSTRACT

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.


Subject(s)
Acute Kidney Injury , COVID-19 , Diabetes Mellitus , Hypertension , Renal Insufficiency, Chronic , Humans , Male , Female , Middle Aged , Adolescent , COVID-19/epidemiology , COVID-19/therapy , COVID-19/complications , Retrospective Studies , Developing Countries , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Acute Kidney Injury/diagnosis , Risk Factors , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/complications , Hypertension/complications , Hospital Mortality
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