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Diabetology & Metabolic Syndrome Dec 2023Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic...
Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial.
BACKGROUND
Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic patients. This study evaluated the effect of canagliflozin on intrarenal lipid content and oxygenation in newly diagnosed type 2 diabetes mellitus (T2DM) patients.
METHODS
A total of 64 newly diagnosed T2DM patients with normal renal function were randomly divided into canagliflozin (n = 33) and glimepiride control (n = 31) groups. All patients underwent functional magnetic resonance imaging (fMRI) scanning to assay patients' intrarenal lipid content and oxygenation level before and after 24 weeks of treatment. Furthermore, the relationship between body mass index and intrarenal lipid content in T2DM patients was analyzed and the correlation between changes in intrarenal lipid content and improvements in renal hypoxia was further assessed.
RESULTS
The canagliflozin group had a greater decrease in body weight and blood uric acid level than the glimepiride group (all P < 0.05). The intrarenal lipid content could be significantly reduced after canagliflozin treatment for 24 weeks. The R2* values, a parameter for quantifying the oxygen content in tissues and is inversely related to the oxygen content, of the renal cortex and medulla in the canagliflozin group decreased from the baseline by 6.40% (P < 0.01) and 12.09% (P = 0.000007), respectively. In addition, the degree of reduction of fat fraction (ΔFF) in the kidneys of the canagliflozin group was correlated with the degree of improvement of oxygenation level (ΔR2*) in the renal cortex (r = 0.422, P = 0.014).
CONCLUSIONS
The early renal protective effect of SGLT2i in newly diagnosed T2DM patients may be partly attributed to the amelioration of renal hypoxia via the alleviation of ectopic lipid deposition in the kidneys.
TRIAL REGISTRATION
Chu Hsien-I Memorial Hospital of Tianjin Medical University (ChiCTR2000037951).
PubMed: 38057876
DOI: 10.1186/s13098-023-01236-1 -
Heliyon Nov 2023Acute kidney injury (AKI) is one of the most common clinical emergencies characterized by rapid progression, difficulty in early diagnosis, and high mortality....
BACKGROUND
Acute kidney injury (AKI) is one of the most common clinical emergencies characterized by rapid progression, difficulty in early diagnosis, and high mortality. Currently, there are no effective AKI early diagnostic methods and treatments. Therefore, identifying new mechanisms of AKI have become urgent for development new targets for early diagnosis and treatment of AKI in the current clinical setting.
METHODS
In this study, systematic analysis and comparison of serum metabolic profiles of clinical AKI patients, chronic kidney disease (CKD) patients, and healthy subjects were performed using untargeted metabolomics. Moreover, the first spatial metabolomic analysis of kidney tissues in an AKI mouse model using MALDI-TOF MS technology was conducted. Differentially expressed metabolites were identified using a comprehensive, publicly available database. The metabolic data obtained were evaluated using principal component analysis, (orthogonal) partial least squares discriminant analysis, and metabolic pathway analysis to explore the unique serum metabolic profile of the patients, as well as to characterize the spatial distribution of differential metabolites in the kidneys of AKI mice.
RESULTS
Significant changes in the metabolite levels of amino acids, carnitine, and lipids were observed in the AKI and CKD groups versus the healthy population, suggesting that kidney injury may lead to abnormalities in various metabolic pathways, such as amino acids, fatty acids, and lipids. The significant difference between the AKI and CKD groups were found for the first time in these indexes including amino acid, carnitine, fatty acid, and lipid levels. Additionally, spatial metabolomics results revealed that amino acid, carnitine, organic acid, and fatty acid metabolites were more likely significantly altered in the renal cortex, while lipid metabolites were both differentially distributed in the cortex and medulla of the AKI group.
CONCLUSION
Abnormalities in the serum metabolism of amino acids, carnitine, and lipids in patients with kidney diseases, such as AKI and CKD, are closely associated with the physiological dysfunction of kidney injury. Metabolic differences between patients with AKI and CKD were compared for the first time, showing that fatty acid oxidative inhibition was more severe in patients with AKI. Furthermore, spatial metabolomics has revealed metabolic reprogramming with tissue heterogeneity in AKI mice model. Our study provides valuable information in the molecular pathological features of AKI in the kidney tissues.
PubMed: 38027662
DOI: 10.1016/j.heliyon.2023.e21171 -
Frontiers in Bioengineering and... 2023Stiffness plays a vital role in diagnosing renal fibrosis. However, perfusion influences renal stiffness in various chronic kidney diseases. Therefore, we aimed to...
Stiffness plays a vital role in diagnosing renal fibrosis. However, perfusion influences renal stiffness in various chronic kidney diseases. Therefore, we aimed to characterize the effect of tissue perfusion on renal stiffness and tissue fluidity measured by tomoelastography based on multifrequency magnetic resonance elastography in an model. Five porcine kidneys were perfused in an MRI-compatible normothermic machine perfusion setup with adjusted blood pressure in the 50/10-160/120 mmHg range. Simultaneously, renal cortical and medullary stiffness and fluidity were obtained by tomoelastography. For the cortex, a statistically significant strong positive correlation was observed between both perfusion parameters (blood pressure and resulting flow) and stiffness (), as well as fluidity (). For the medulla, such significant ( correlations were solely observed between the perfusion parameters and stiffness (). Our findings demonstrate a strong perfusion dependency of renal stiffness and fluidity in an setup. Moreover, changes in perfusion are rapidly followed by changes in renal mechanical properties-highlighting the sensitivity of tomoelastography to fluid pressure and the potential need for correcting mechanics-derived imaging biomarkers when addressing solid structures in renal tissue.
PubMed: 38026891
DOI: 10.3389/fbioe.2023.1236949 -
Cureus Oct 2023A neonate with acute kidney injury can present with decreased urine output and signs of dehydration. Sonography is used to evaluate the kidneys for structural...
A neonate with acute kidney injury can present with decreased urine output and signs of dehydration. Sonography is used to evaluate the kidneys for structural deformities. A normal sonographic image of a neonatal kidney would show hypoechoic pyramids of the medulla. However, less frequently occurring neonatal transient renal failure with renal medullary hyperechogenicity has been linked to severe perinatal renal damage, kidney abnormalities, or nephrocalcinosis. A simple conventional sonography in neonates can be helpful in predicting the severity of renal damage in such cases. Hyperechogenecity of the medulla in contrast to the normal hypoechogenic medulla of normal neonates can be due to multiple causes. However one must bear in mind that this finding of hyperechoic tips of renal pyramids is not indicative of intrinsic renal disease and subsides without intervention if physiologic or with rehydration if due to hypernatraemic dehydration. It is important for a physician to know about this physiological variant seen in neonates who present with dehydration.
PubMed: 38022215
DOI: 10.7759/cureus.47508 -
Scientific Reports Nov 2023T cells are important in the pathogenesis of acute kidney injury (AKI), and TCRCD4CD8 (double negative-DN) are T cells that have regulatory properties. However, there is...
T cells are important in the pathogenesis of acute kidney injury (AKI), and TCRCD4CD8 (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4 and CD8 cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4, and CD8 cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for DN, CD4, and CD8 T cells of mouse kidneys with enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T cells compared to CD4 and CD8 T cells in normal kidney tissue. We validated the expression of these four genes in mouse kidney DN, CD4 and CD8 T cells using RT-PCR and Kcnq5, Klrb1, and Fcer1g genes with the NIH human kidney precision medicine project (KPMP). Spatial transcriptomics in normal and ischemic mouse kidney tissue showed a localized cluster of T cells in the outer medulla expressing DN T cell genes including Fcer1g. These results provide a template for future studies in DN T as well as CD4 and CD8 cells in normal and diseased kidneys.
Topics: Humans; Animals; Mice; CD8-Positive T-Lymphocytes; Transcriptome; CD8 Antigens; CD4 Antigens; Kidney; Acute Kidney Injury; Receptors, Antigen, T-Cell, alpha-beta
PubMed: 38017015
DOI: 10.1038/s41598-023-48213-2 -
Veterinary Sciences Oct 2023The objective of this study was to assess changes in the echogenicity of the cortex and medulla of canine fetal kidneys in relation to days before parturition (dbp),...
The objective of this study was to assess changes in the echogenicity of the cortex and medulla of canine fetal kidneys in relation to days before parturition (dbp), maternal size and litter size. Monitoring of 10 healthy pregnant bitches (2-8 years old, 8.8-40.3 kg bw) was conducted from -10 to 0 dbp using ultrasound. A single renal sonogram was obtained by scanning in a longitudinal section the three most caudal fetuses. The mean gray level (MGL) and SD of a manually drawn region of interest (ROI) in the renal cortex and medulla were measured using the Fiji Image J software (Image J 1.51h, Java 1.6 0_24 64 bit). A linear mixed model taking into account the maternal size as a fixed effect, dbp and litter size as covariates and the bitch as a random and repeated effect was used. The regression coefficients (b) were estimated. Cortical SD (C-SD) and cortico-medullary SD (C/M-SD) were influenced by dbp, with a significant decrease at the approaching day of parturition (b = 0.23 ± 0.06, < 0.001 and b = 0.5 ± 0.02, = 0.038, respectively). Maternal size had a significant impact on C/M-MGL with differences observed in large-sized (1.95 ± 0.13) compared to small- (1.41 ± 0.10, = 0.027) and medium-sized bitches (1.51 ± 0.09, = 0.016). The C/M-MGL was influenced by litter size, showing a decrease as the number of pups increased (b = -0.08 ± 0.03, = 0.018). C-SD and C/M-SD were exclusively affected by dbp, and not by maternal and litter size. This suggests their potential as valuable parameters, warranting further investigations in future studies.
PubMed: 37999462
DOI: 10.3390/vetsci10110639 -
Cureus Oct 2023Pheochromocytomas are rare tumors that arise from the sympathetic ganglia or adrenal medulla and secrete catecholamines that are known for the classic triad of...
Pheochromocytomas are rare tumors that arise from the sympathetic ganglia or adrenal medulla and secrete catecholamines that are known for the classic triad of headaches, profuse sweating, and paroxysmal hypertension. However, there have been instances of asymptomatic patients found to have a pheochromocytoma. Adrenal incidentalomas are accidentally discovered through radiologic imaging, and subsequent testing can confirm a pheochromocytoma. Here, we present a case of a 67-year-old female found to have an adrenal incidentaloma on kidney ultrasound (US) after presenting to the emergency room (ER) due to nausea. She had minimally elevated creatinine at the ER. At her follow-up with her primary care provider (PCP), a kidney US was ordered and showed a probable right suprarenal mass. Further abdominal computed tomography (CT) and abdominal magnetic resonance imaging (MRI) showed that the mass was indeed adrenal, but its etiology is considered indeterminant. Although asymptomatic, further biochemical tests showed elevated serum and urine metanephrines and normetanephrines. Together, these findings revealed that the adrenal mass was likely a silent pheochromocytoma. She underwent a successful right adrenalectomy with pathology confirming pheochromocytoma. This case adds to the literature on the existence of silent pheochromocytomas and highlights the importance of following up on any abnormal findings with a PCP. This patient, although asymptomatic from her pheochromocytoma, needed surgery to prevent possible pheochromocytoma crises, which could cause cardiovascular complications and even death.
PubMed: 37954727
DOI: 10.7759/cureus.46915 -
Internal Medicine (Tokyo, Japan) Jun 2024Renal medullary angiitis is characterized by interstitial hemorrhaging in the medulla with neutrophil infiltration. An 81-year-old man presented with a fever, kidney...
Renal medullary angiitis is characterized by interstitial hemorrhaging in the medulla with neutrophil infiltration. An 81-year-old man presented with a fever, kidney dysfunction, and purpura of the legs, which was diagnosed as leukocytoclastic vasculitis. Proteinase 3 antineutrophil cytoplasmic antibodies were weakly positive. A kidney biopsy showed severe tubulointerstitial hemorrhaging with neutrophilic infiltration in the perivascular areas surrounding the vasa recta in the medulla without crescent formation in the glomeruli. An immunofluorescence analysis was negative, and electron microscopy revealed no immune-dense deposits, ruling out immunoglobulin A vasculitis. Intravenous methylprednisolone for three days and plasma exchange followed by oral prednisolone improved his general condition.
Topics: Humans; Male; Aged, 80 and over; Vasculitis, Leukocytoclastic, Cutaneous; Methylprednisolone; Kidney Medulla; Plasma Exchange; Prednisolone; Vasculitis
PubMed: 37926537
DOI: 10.2169/internalmedicine.2679-23 -
Alternative Therapies in Health and... Nov 2023Both functional magnetic resonance imaging and renal tubular injury markers have been proved to be able to detect early renal damage in normoalbuminuric diabetic...
OBJECTIVE
Both functional magnetic resonance imaging and renal tubular injury markers have been proved to be able to detect early renal damage in normoalbuminuric diabetic patients. This study mainly explored the functional magnetic resonance imaging parameters and renal tubular injury markers in the early evaluation of type 2 diabetes.
METHODS
A case observation study was established, and 62 patients with early-stage low-risk type 2 diabetes mellitus with normoalbuminuric (UACR<30 mg/g, eGFR≥60 ml/min/1.73 m2) were included for analysis. Urine kidney damage was determined by ELISA. Kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) assessment of renal tubular injury, and use of intravoxel incoherent motion magnetic resonance Imaging (intravoxel incoherent motion, IVIM) and blood oxygen level dependent magnetic resonance imaging (blood oxygen level dependent, BOLD) to evaluate renal cortex, medulla blood perfusion, water molecule diffusion, oxygenation level and other functional information, using linear correlation to analyze the correlation between functional magnetic resonance imaging parameters and markers of renal tubular injury.
RESULTS
The correlation analysis between IVIM parameters and renal tubular injury markers showed that KIM-1 was inversely correlated with the MD value of the renal medulla region parameter (r = -0.24, P = .03), and was closely related to the other IVIM cortex and medulla. There was no correlation between qualitative parameters (P > .05), and no correlation between NGAL and all parameters of IVIM (P > .05). The correlation analysis between BOLD parameters and renal tubular injury markers showed that KIM-1 was positively correlated with renal medulla region parameter MR2* value (r = 0.26, P = .04) and MCR value (r = 0.28, P = .03), respectively. There was also a positive correlation between NGAL and renal medulla region parameter MR2* value (r = 0.24, P = .04).
CONCLUSION
In the early low-risk type 2 diabetic patients with normoalbuminuria, the more obvious the renal medullary water molecule diffusion disorder, the higher the renal tubular injury marker KIM-1, and the more severe renal medullary hypoxia, the renal tubular injury. The higher the markers KIM-1 and NGAL are, it is proved that the hypoxia and water diffusion disorder in the early renal medulla are related to renal tubular damage.
PubMed: 37917906
DOI: No ID Found -
Clinical Kidney Journal Nov 2023For decades, description of renal function has been of interest to clinicians and researchers. Serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) are...
BACKGROUND
For decades, description of renal function has been of interest to clinicians and researchers. Serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) are familiar but also limited in many circumstances. Meanwhile, the physiological volumes of the kidney cortex and medulla are presumed to change with age and have been proven to change with decreasing kidney function.
METHODS
We recruited 182 patients with normal Scr levels between October 2021 and February 2022 in Peking Union Medical College Hospital (PUMCH) with demographic and clinical data. A 3D U-Net architecture is used for both cortex and medullary separation, and volume calculation. In addition, we included patients with the same inclusion criteria but with diabetes (PUMCH-DM test set) and diabetic nephropathy (PUMCH-DN test set) for internal comparison to verify the possible clinical value of "kidney age" (K-AGE).
RESULTS
The PUMCH training set included 146 participants with a mean age of 47.5 ± 7.4 years and mean Scr 63.5 ± 12.3 μmol/L. The PUMCH test set included 36 participants with a mean age of 47.1 ± 7.9 years and mean Scr 66.9 ± 13.0 μmol/L. The multimodal method predicted K-AGE approximately close to the patient's actual physiological age, with 92% prediction within the 95% confidential interval. The mean absolute error increases with disease progression (PUMCH 5.00, PUMCH-DM 6.99, PUMCH-DN 9.32).
CONCLUSION
We established a machine learning model for predicting the K-AGE, which offered the possibility of evaluating the whole kidney health in normal kidney aging and in disease conditions.
PubMed: 37915907
DOI: 10.1093/ckj/sfad167