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PloS One 2024Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress,...
Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects of betaine in normotensive and hypertensive rats. Betaine levels were assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats (Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis were evaluated. Gene and protein expression of chosen kidney betaine transporters (SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared to normotensive rats, SHRs showed significantly lower concentration of betaine in blood serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p = 0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial blood pressure. The diuretic response was greater in SHRs than in WKYs. There were no significant differences in renal expression of betaine transporters between WKYs and SHRs. Increased renal excretion of betaine contributes to decreased concentration of the protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies evaluating a causal relation between depleted betaine and hypertensive organ damage, including kidney injury.
Topics: Rats; Animals; Betaine; Rats, Inbred WKY; Diuretics; Renal Elimination; Hypertension; Kidney; Rats, Inbred SHR; Blood Pressure; Electrolytes
PubMed: 38166023
DOI: 10.1371/journal.pone.0294926 -
International Journal of Medical... 2024This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. This prospective study included...
This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.
Topics: Humans; Prospective Studies; Kidney Transplantation; Contrast Media; Kidney; Ultrasonography
PubMed: 38164356
DOI: 10.7150/ijms.88147 -
Environmental Science & Technology Jan 2024Human exposure to perfluorinated alkylate substances (PFASs) is usually assessed from the concentrations in serum or plasma, assuming one-compartment toxicokinetics. To...
Human exposure to perfluorinated alkylate substances (PFASs) is usually assessed from the concentrations in serum or plasma, assuming one-compartment toxicokinetics. To characterize body distributions of major PFASs, we obtained and extracted tissue samples from 19 forensic autopsies of healthy adult subjects who had died suddenly and were not known to have elevated levels of PFAS exposure. As target organs of toxicological importance, we selected the liver, kidneys, lungs, spleen, and brain, as well as whole blood. Samples weighing about 0.1 g were analyzed by liquid chromatography coupled to triple mass spectrometers. Minor variations in PFAS concentrations were found between the kidney cortex and medulla and between lung lobes. Organ concentrations of perfluorooctanoic sulfonate (PFOS) and perfluorononanoate (PFNA) correlated well with blood concentrations, while perfluorooctanoate (PFOA) and perfluorohexanoic sulfonate (PFHxS) showed more variable associations. Likewise, the liver concentrations correlated well with those of other organs. Calculations of relative distributions were carried out to assess the interdependence of organ retentions. Equilibrium model predictions largely explained the observed PFAS distributions, except for the brain. Although the samples were small and affected by a possible lack of homogeneity, these findings support the use of blood-PFAS concentrations as a measure of PFAS exposure, with the liver possibly acting as the main organ of retention.
Topics: Adult; Humans; Environmental Pollutants; Alkanesulfonic Acids; Alkanesulfonates; Plasma; Fluorocarbons
PubMed: 38154793
DOI: 10.1021/acs.est.3c06499 -
Magnetic Resonance in Medical Sciences... Dec 2023The objective of this study was to evaluate renal function and pathologic injury in chronic kidney disease (CKD) using T1 mapping.
PURPOSE
The objective of this study was to evaluate renal function and pathologic injury in chronic kidney disease (CKD) using T1 mapping.
METHODS
We recruited fifteen healthy volunteers (HV) and seventy-five CKD patients to undergo T1 mapping examination, and renal parenchymal T1 values were measured. Spearman correlation analysis was used to evaluate the relevance between the pathologic injury score, estimated glomerular filtration rate (eGFR), and renal parenchymal T1 values. The diagnostic efficiency of T1 value in evaluating renal pathologic impairment was assessed.
RESULTS
In all subjects, renal cortical T1 value was remarkably lower than renal medullary T1 value (P < 0.01). The renal medullary T1 value of HV was considerably lower than that of CKD patients in all stages (P < 0.05). The T1 values were negatively correlated with eGFR (cortex, r = -0.718; medulla, r = -0.645). The T1 values were positively correlated with glomerular injury score (cortex, r = 0.692; medulla, r = 0.632), tubulointerstitial injury score (cortex, r = 0.758; medulla, r = 0.690) (all P < 0.01). The area under the curve (AUC) of renal cortical and medullary T1 values were 0.914 and 0.880 to distinguish moderate-severe from mild renal injury groups. To differentiate mild renal injury group from control group, the AUC values of renal cortical and medullary T1 values were 0.879 and 0.856.
CONCLUSION
T1 mapping has potential application value in non-invasively assessing renal pathologic injury in CKD.
PubMed: 38143088
DOI: 10.2463/mrms.mp.2023-0027 -
Nature Communications Dec 2023Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial...
Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.
Topics: Humans; Ferroptosis; Kidney; Acute Kidney Injury; Autophagy; Reperfusion Injury; Ischemia
PubMed: 38110369
DOI: 10.1038/s41467-023-44228-5 -
Quantitative Imaging in Medicine and... Dec 2023Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the...
BACKGROUND
Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model.
METHODS
AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTR), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage.
RESULTS
Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression.
CONCLUSIONS
The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.
PubMed: 38106319
DOI: 10.21037/qims-23-699 -
IScience Dec 2023Renal medullary aquaporin-1 (AQP1) plays an important role in the urinary concentration. This study aimed to investigate the regulation of AQP1 by low osmotic stress and...
Renal medullary aquaporin-1 (AQP1) plays an important role in the urinary concentration. This study aimed to investigate the regulation of AQP1 by low osmotic stress and a potential role of autophagy. Low osmotic stress induced a dramatically decreased AQP1 protein expression in murine inner medullary collecting duct 3 (mIMCD3) cells, which was associated with a marked activation of autophagy. Inhibition of autophagy by 3-methyladenine (3-MA), chloroquine, or knockdown of autophagy-related protein 5 (ATG5) prevented the decrease in AQP1 protein abundance. Rapamycin-induced autophagy was associated with a decreased AQP1 protein expression and an enhanced interaction between AQP1 and ATG5 in mIMCD3 cells under low osmotic stress. In kidney inner medulla of mice given a 3% NaCl solution, activation of autophagy was associated with decreased AQP1 protein expression, which was prevented by 3-MA. In conclusion, low osmotic stress induced autophagy which contributed to the decreased AQP1 protein expression in the renal medulla.
PubMed: 38094243
DOI: 10.1016/j.isci.2023.108485 -
Case Reports in Urology 2023Pheochromocytoma is a rare neoplasia arising from the adrenal medulla that secretes catecholamines. Those afflicted by this condition can present a wide range of...
INTRODUCTION
Pheochromocytoma is a rare neoplasia arising from the adrenal medulla that secretes catecholamines. Those afflicted by this condition can present a wide range of symptoms. One of the most common is paroxysmic hypertension. Interestingly, although rare, some patients present with shock. We describe two cases of pheochromocytoma in which the initial presentation was shock. . 49 year-old woman, with a history of resistant hypertension, presented to the emergency department with thoracic pain and fever. EKG, echocardiogram (ECC), and myocardial necrosis markers were compatible with Takotsubo syndrome (TS). CT demonstrated a staghorn calculus, hydronephrosis, and signs compatible with xanthogranulomatous pyelonephritis in the right kidney. Additionally, and incidentally, it revealed a 60 mm nodule on the right adrenal gland. Piperacillin/tazobactam was started immediately, and the patient was submitted to urgent upper urinary tract drainage. This procedure was complicated by a cardiorespiratory arrest that was treated with adrenaline administration. The patient was admitted to the ICU due to multifactorial shock and started alpha and, posteriorly, beta blockage. Biochemical adrenal incidentaloma endocrinologic study was negative (under hemodialysis). Multiorgan failure progressively improved. After 2 weeks, the patient was submitted to a laparoscopic transperitoneal right adrenalectomy. No complications were reported. Histological analysis revealed a pheochromocytoma. . 28-year-old woman presented to the emergency department with headaches and nausea. Vitals were compatible with shock. CT revealed an incidental 72 mm mass on the right adrenal. EKG, ECC, and myocardial necrosis markers were compatible with TS. The patient was started on alpha and, posteriorly, beta blockage. Adrenal incidentaloma endocrinological study demonstrated high urinary catecholamines. Right transperitoneal adrenalectomy was performed. No complications were noted. Histological analysis revealed a pheochromocytoma.
CONCLUSION
Pheochromocytoma can present with complex, enigmatic, and rare clinical pictures. Clinicians should be wary of the possibility of this diagnosis when managing adrenal masses.
PubMed: 38073711
DOI: 10.1155/2023/8901383 -
Journal of Clinical Medicine Nov 2023Multiparametric renal Magnetic Resonance Imaging (MRI) provides a non-invasive method to assess kidney structure and function, but longitudinal studies are limited.
BACKGROUND
Multiparametric renal Magnetic Resonance Imaging (MRI) provides a non-invasive method to assess kidney structure and function, but longitudinal studies are limited.
METHODS
A total of 22 patients with CKD category G3-4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m) were recruited. Annual 3T multiparametric renal MRI scans were performed, comprising total kidney volume (TKV), longitudinal relaxation time (T), apparent diffusion coefficient (ADC), Arterial Spin Labelling, and Blood Oxygen Level Dependent relaxation time (T*), with 15 patients completing a Year 2 scan. CKD progression over 2 years was defined as eGFR_slope ≥ -5 mL/min/1.73 m/year.
RESULTS
At baseline, T was higher (cortex = 0.05, medulla = 0.03) and cortex perfusion lower ( = 0.015) in participants with subsequent progression versus stable eGFR. A significant decrease in TKV and ADC and an increase in cortex T occurred in progressors at Year 1 and Year 2, with a significant decrease in perfusion in progressors only at Year 2. The only decline in the stable group was a reduction in TKV. There was no significant change in cortex or medulla T* at Year 1 or Year 2 for progressors or stable participants.
CONCLUSION
Lower renal cortex perfusion and higher T in the cortex and medulla may predict CKD progression, while renal cortex T, TKV, and ADC may be useful to monitor progression. This study provides pilot data for future large-scale studies.
PubMed: 38068333
DOI: 10.3390/jcm12237282 -
American Journal of Physiology. Renal... Feb 2024The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead... (Observational Study)
Observational Study
The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgHO). Plasma ADH was positively associated with plasma tonicity and natremia ( < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule. The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.
Topics: Humans; Diabetes Insipidus, Nephrogenic; Polyuria; Diuresis; Osmolar Concentration; Antidiuretic Agents; Water; Anemia, Sickle Cell; Diabetes Insipidus; Diabetes Mellitus
PubMed: 38059298
DOI: 10.1152/ajprenal.00313.2023