-
Urolithiasis Jun 2024We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of... (Randomized Controlled Trial)
Randomized Controlled Trial
We aimed to determine the effect of the access sheath diameter used in percutaneous nephrolithotomy (PNL) on renal function. We also investigated the predictors of impaired renal function. Data were prospectively collected from patients who underwent PNL from December 2020 to December 2021. The patients were randomized into two groups according to access sheath diameter: Group 1 (22 Fr, n = 44) and Group 2 (28 Fr, n = 44). Relative renal function (RRF) was calculated by technetium-99 m dimercaptosuccinic acid scintigraphy, and glomerular filtration rate (GFR) was calculated by diethylenetriamine pentaacetic acid scintigraphy. A difference of 5% or more in RRF was considered a significant functional change. Preoperative and postoperative Kidney Injury Molecule-1 (KIM-1) levels were measured. Preoperative demographic data and stone characteristics were similar between the groups. There were also no statistically significant differences between the groups in terms of scar development, changes in RRF, GFR, or KIM-1/creatinine (Cr) (p > 0.05). Significant deterioration in RRF was detected in a total of six (6.8%) patients, three in each group. The factors predicting loss of function were analyzed by regrouping the patients without loss of function as Group A (n = 82) and those with loss as Group B (n = 6). Only stone volume was statistically significant in multivariate analysis (p = 0.002). Access sheath diameter had no significant effect on renal function after PNL. However, the stone volume was found to independently correlate to a loss of renal function after PNL.
Topics: Humans; Male; Female; Nephrolithotomy, Percutaneous; Prospective Studies; Middle Aged; Kidney Calculi; Adult; Kidney; Glomerular Filtration Rate; Equipment Design; Kidney Function Tests
PubMed: 38922347
DOI: 10.1007/s00240-024-01582-3 -
Critical Care Explorations Jul 2024COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked...
IMPORTANCE
COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.
OBJECTIVES
To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.
DESIGN, SETTING, AND PARTICIPANTS
The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.
MAIN OUTCOMES AND MEASURES
We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.
RESULTS
At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.
CONCLUSIONS
Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.
Topics: Humans; COVID-19; Middle Aged; Critical Illness; Male; Acute Kidney Injury; Female; Prospective Studies; Aged; Hepatitis A Virus Cellular Receptor 1; SARS-CoV-2; Adult; Biomarkers; Kidney Tubules; Creatinine; Intensive Care Units; Washington; Epidermal Growth Factor; Renal Replacement Therapy
PubMed: 38922318
DOI: 10.1097/CCE.0000000000001109 -
Toxins May 2024Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could... (Review)
Review
Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial dysbiosis in individuals with CKD. This narrative review explores the underlying mechanisms through which physical activity may favorably modulate microbial health, either through direct impact on the gut or through interorgan crosstalk. Also, the development of microbial dysbiosis and its interplay with physical inactivity in patients with CKD are discussed. Mechanisms and interventions through which physical activity may restore gut homeostasis in individuals with CKD are explored.
Topics: Gastrointestinal Microbiome; Humans; Renal Insufficiency, Chronic; Dysbiosis; Exercise; Animals
PubMed: 38922137
DOI: 10.3390/toxins16060242 -
Medical Sciences (Basel, Switzerland) Jun 2024Hemodialyzed patients have innate immunity activation and adaptive immunity senescence. Diabetes mellitus is a frequent cause for chronic kidney disease and systemic...
Hemodialyzed patients have innate immunity activation and adaptive immunity senescence. Diabetes mellitus is a frequent cause for chronic kidney disease and systemic inflammation. We studied the immunological pattern (innate and acquired immunity) and the tissular regeneration capacity in two groups of hemodialyzed patients: one comprised of diabetics and the other of non-diabetics. For inflammation, the following serum markers were determined: interleukin 6 (IL-6), interleukin 1β (IL-1β), tumoral necrosis factor α (TNF-α), IL-6 soluble receptor (sIL-6R), NGAL (human neutrophil gelatinase-associated lipocalin), and interleukin 10 (IL-10). Serum tumoral necrosis factor β (TNF-β) was determined as a cellular immune response marker. Tissue regeneration capacity was studied using neurotrophin-3 (NT-3) and vascular endothelial growth factor β (VEGF-β) serum levels. The results showed important IL-6 and sIL-6R increases in both groups, especially in the diabetic patient group. IL-6 generates trans-signaling at the cellular level through sIL-6R, with proinflammatory and anti-regenerative effects, confirmed through a significant reduction in NT-3 and VEGF-β. Our results suggest that the high serum level of IL-6 significantly influences IL-1β, TNF-β, NT-3, VEGF-β, and IL-10 behavior. Our study is the first that we know of that investigates NT-3 in this patient category. Moreover, we investigated VEGF-β and TNF-β serum behavior, whereas most of the existing data cover only VEGF-α and TNF-α in hemodialyzed patients.
Topics: Humans; Renal Dialysis; Male; Interleukin-6; Female; Middle Aged; Neurotrophin 3; Aged; Tumor Necrosis Factor-alpha; Receptors, Interleukin-6; Diabetes Mellitus; Lipocalin-2; Interleukin-1beta; Regeneration; Biomarkers; Immunity, Innate; Inflammation; Adult
PubMed: 38921685
DOI: 10.3390/medsci12020031 -
Marine Drugs Jun 2024Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a...
Cadmium (Cd) is a toxic heavy metal that causes nephrosis, including acute kidney injury. To prevent and treat acute kidney injury (AKI) following Cd exposure, a tripeptide, Ser-Arg-Pro (SRP), from L. was employed, and its potential efficacy in AKI was assessed. Oral administration of SRP significantly alleviated Cd-induced kidney damage, leading to improved renal function and the attenuation of structural abnormalities. A network pharmacology analysis revealed the potential of SRP in renal protection by targeting various pathways, including mitogen-activated protein kinase (MAPK) signaling, inflammatory response, and apoptosis pathways. Mechanistic studies indicated that SRP achieves renal protection by inhibiting the activation of MAPK pathways (phosphorylation of p38, p56, ERK, and JNK) in the oxidative stress cascade, suppressing inflammatory responses (iNOS, Arg1, Cox2, TNF-α, IL-1β, and IL-6), and restoring altered apoptosis factors (caspase-9, caspase-3, Bax, and Bcl-2). Hence, SRP has the potential to be used as a therapeutic agent for the treatment of Cd-induced nephrotoxicity.
Topics: Animals; Acute Kidney Injury; Apoptosis; Mice; Cadmium; Oxidative Stress; Male; Oligopeptides; MAP Kinase Signaling System; Kidney; Inflammation; Disease Models, Animal; Network Pharmacology
PubMed: 38921597
DOI: 10.3390/md22060286 -
Journal of Functional Biomaterials Jun 2024Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the...
Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the Biopharmaceutics Classification System. It is practically insoluble in water. This study aimed to optimize and formulate porous orally disintegrating tablets (ODTs) prepared by sublimation and loaded with FUR nanoparticles prepared by using a planetary ball mill. Different functional biomaterials called stabilizers were used to stabilize the nanoparticle formula. Pluronic F-127 was the optimum stabilizer in terms of particle size (354.07 ± 6.44), zeta potential (-25.3 ± 5.65), and dissolution efficiency (56.34%). The impact of the stabilizer concentration was studied as well, and a concentration of 3% showed the smallest particle size (354.07 ± 6.44), best zeta potential value (-25.3 ± 5.65), and percentage of dissolution rate (56.34%). A FUR-loaded nanoparticle formula was successfully prepared. The nanoparticle formula was stabilized by using 3% pluronic F-127, and 3% was chosen for further study of the incorporation into oral disintegration tablets prepared by the sublimation technique. The impact of the matrix sublimating agent and superdisintegrant on the ODTs' attributes (in vitro disintegration, wetting time, and in vitro dissolution efficiency) was studied using 3 full factorial designs. , the diuretic activity was tested for the optimized FUR ODTs by calculating the Lipschitz value using rats as an animal model. The stability of the ODTs loaded with FUR nanoparticles was assessed under accelerated conditions for 6 months. Finally, the ODT formula loaded with FUR NPs showed a rapid onset of action that was significantly faster than untreated drugs. Nanonization and ODT formulation enhances the dissolution rate and bioavailability of FUR. Many factors can be controlled to achieve optimization results, including the formulation and process parameters.
PubMed: 38921534
DOI: 10.3390/jfb15060161 -
Healthcare (Basel, Switzerland) Jun 2024Evaluation of post-nephrectomy social health in living kidney donors is essential. This systematic review examines their emotional need for social relatedness... (Review)
Review
INTRODUCTION
Evaluation of post-nephrectomy social health in living kidney donors is essential. This systematic review examines their emotional need for social relatedness post-donation.
METHODS
Following the PRISMA guidelines, we systematically searched Scopus, CINAHL, and PsycINFO.
RESULTS
Among the screened records, 32 quantitative and 16 qualitative papers met the inclusion criteria. Quantitative research predominantly utilized questionnaires featuring generic items on social functioning. However, a minority delved into emotional and social dimensions, aligning with qualitative studies emphasizing the importance of social connection and perceived social support post-donation. Specifically, post-donation changes in connecting with others encompass a sense of belongingness, heightened autonomy, shifts in concern for the recipient's health, and continued care by shielding the recipient from personal health issues. Social acknowledgment and social support from both close and extended networks are reported as relevant for recovery after nephrectomy.
DISCUSSION
These findings underscore the necessity for targeted measures of emotional needs and social functioning to effectively assess post-donation adjustment. They also inform the identification of key health themes for kidney donor Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) questions.
PubMed: 38921330
DOI: 10.3390/healthcare12121216 -
Current Issues in Molecular Biology May 2024The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family...
The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein-protein interactions, we also chose a collection of well-known functional protein partners for pleckstrin. Investigations were also carried out on the relationship between pleckstrins and other cancers regarding mutations and copy number alterations. The cumulative impact of pleckstrin and their associated genes on various cancers, Gene Ontology (GO), and pathway analyses were used for their evaluation. Thus, the expression profiles of PHLDA family members and their prognosis in various cancers may be revealed by this study. During this multiomics analysis, we found that among the PHLDA family, PHLDA1 may be a therapeutic target for several cancers, including kidney, colon, and brain cancer, while PHLDA2 can be a therapeutic target for cancers of the colon, esophagus, and pancreas. Additionally, PHLDA3 may be a useful therapeutic target for ovarian, renal, and gastric cancer.
PubMed: 38921000
DOI: 10.3390/cimb46060328 -
Cells Jun 2024The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or... (Review)
Review
The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or in combination for solid tumors such as renal cell carcinoma or breast cancer. However, despite the high prevalence of PI3K pathway alterations in gynecological cancers and promising preclinical activity in endometrial and ovarian cancer models, PI3K pathway inhibitors showed limited clinical activity in gynecological cancers. In this review, we provide an overview on resistance mechanisms against PI3K pathway inhibitors that limit their use in gynecological malignancies, including genetic alterations that reactivate the PI3K pathway such as mutations and loss, compensatory signaling pathway activation, and feedback loops causing the reactivation of the PI3K signaling pathway. We also discuss the successes and limitations of recent clinical trials aiming to address such resistance mechanisms through combination therapies.
Topics: Humans; Female; Genital Neoplasms, Female; Drug Resistance, Neoplasm; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Animals
PubMed: 38920692
DOI: 10.3390/cells13121064 -
Cells Jun 2024The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds....
The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1). Organic cation and anion transport were studied using the fluorescent substrates 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) and 6-carboxyfluorescein (6-CF), respectively. The level and rate of intracellular ASP accumulation in PTL following basolateral application were slightly lower but within a 3-fold range compared to primary PTEC and RPTEC/TERT1 cells. The basolateral uptake of ASP and its subsequent apical efflux could be inhibited by basolateral exposure to quinidine in all models. Of the three models, only PTL showed a modest preferential basolateral-to-apical 6-CF transfer. These results show that organic cation transport could be demonstrated in all three models, but more research is needed to improve and optimise organic anion transporter expression and functionality.
Topics: Humans; Kidney Tubules, Proximal; Epithelial Cells; Models, Biological; Pyridinium Compounds; Anions; Induced Pluripotent Stem Cells; Biological Transport; Organic Anion Transporters; Cell Line; Cations; Fluoresceins; Organic Cation Transport Proteins
PubMed: 38920639
DOI: 10.3390/cells13121008