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Frontiers in Endocrinology 2023Chronic kidney disease (CKD) is a complex syndrome with high morbidity and slow progression. Early stages of CKD are asymptomatic and lack of awareness at this stage...
BACKGROUND
Chronic kidney disease (CKD) is a complex syndrome with high morbidity and slow progression. Early stages of CKD are asymptomatic and lack of awareness at this stage allows CKD to progress through to advanced stages. Early detection of CKD is critical for the early intervention and prognosis improvement.
PURPOSE
To assess the capability of mDIXON-Quant imaging to detect early CKD and evaluate the degree of renal damage in patients with CKD.
STUDY TYPE
Retrospective.
POPULATION
35 patients with CKD: 18 cases were classifified as the mild renal damage group (group A) and 17 cases were classifified as the moderate to severe renal damage group (group B). 22 healthy volunteers (group C).
FIELD STRENGTH/SEQUENCE
A 3.0 T/TWI, TWI and mDIXON-Quant sequences.
ASSESSMENT
Transverse relaxation rate (R2*) values and fat fraction (FF) values derived from the mDIXON-Quant were calculated and compared among the three groups.
STATISTICAL TESTS
The intra-class correlation (ICC) test; Chi-square test or Fisher's exact test; Shapiro-Wilk test; Kruskal Wallis test with adjustments for multiplicity (Bonferroni test); Area under the receiver operating characteristic (ROC) curve (AUC). The significance threshold was set at P < 0.05.
RESULTS
Cortex FF values and cortex R2* values were significantly different among the three groups (P=0.028, <0.001), while medulla R2* values and medulla FF values were not (P=0.110, 0.139). Cortex FF values of group B was significantly higher than that of group A (Bonferroni adjusted P = 0.027). Cortex R2* values of group A and group B were both significantly higher than that of group C (Bonferroni adjusted P = 0.012, 0.001). The AUC of cortex FF values in distinguishing group A and group B was 0.766. The diagnostic efficiency of cortex R2* values in distinguishing group A vs. group C and group B vs. group C were 0.788 and 0.829.
CONCLUSION
The mDIXON-Quant imaging had a potential clinical value in early diagnosis of CKD and assessing the degree of renal damage in CKD patients.
Topics: Humans; Retrospective Studies; Magnetic Resonance Imaging; Kidney; Renal Insufficiency, Chronic; Adipose Tissue
PubMed: 37547308
DOI: 10.3389/fendo.2023.1187042 -
FEBS Open Bio Oct 2023Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of...
Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In the present study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation. The expression and localization of PRMT1 and molecules involved in the transforming growth factor (TGF)-β1/Smad3 and interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathways were detected in mouse kidney tissues by western blot analysis, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways was further verified in vitro in mouse renal tubular epithelial cells. Cecal ligation and perforation caused epithelial-mesenchymal transition, apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of soluble IL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mouse renal tubular epithelial cells restricted the expression of Cox-2, E-cadherin, Pro-caspase3, and phosphorylated Smad3 (involved in the TGF-β1-mediated signaling pathway), and also blocked IL-6/soluble IL-6R, inducing the expression of Cox-2 and phosphorylated-STAT3. In conclusion, our findings suggest that inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and the IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.
Topics: Mice; Animals; Transforming Growth Factor beta1; Interleukin-6; Cyclooxygenase 2; Acute Kidney Injury; Signal Transduction; Sepsis
PubMed: 37525933
DOI: 10.1002/2211-5463.13684 -
Experimental and Therapeutic Medicine Aug 2023Patients with primary central nervous system lymphoma (PCNSL) typically present with non-focal neurological symptoms, including disorientation, poor balance and memory...
Patients with primary central nervous system lymphoma (PCNSL) typically present with non-focal neurological symptoms, including disorientation, poor balance and memory loss with unifocal or multifocal periventricular lesions seen on MRI. Deviations from these characteristic findings can delay diagnosis and lead to additional diagnostic tests being needed. The present study reports a 68-year-old man with a recent varicella zoster infection and history of acetylcholine receptor antibody-positive myasthenia gravis who received mycophenolate mofetil for 22 years. He presented with left eye vision changes and cognitive memory deficits. A brain MRI showed an enhancing lesion within his left medulla extending to the cerebellum. Cerebrospinal fluid analysis was positive for Epstein-Barr virus (EBV) and negative for malignancy. He was diagnosed with varicella zoster virus vasculopathy. At 3 months later, a repeat brain MRI showed multiple new enhancing lesions developing bilaterally along the periventricular white matter. Soon after, he presented to a local ER with acute left-sided blurry vision and worsening memory loss, and he began receiving steroids. Because of rapid symptom progression, he underwent resection of the left frontal lesion, which showed EBV-induced diffuse large B-cell lymphoma (DLBCL). Mycophenolate mofetil was discontinued, and within 24 h of one dose of intravenous 500 mg/m rituximab, he had a dramatic improvement in left eye vision and memory loss. He experienced mixed responses to rituximab after 3 cycles. Following one dose of high-dose methotrexate, he developed subsequent chronic kidney disease and required dialysis. He received whole-brain radiation therapy with craniospinal radiation and is currently in complete remission. An EBV-induced DLBCL diagnosis should be highly considered for patients with periventricular lesions and EBV-positive cerebrospinal fluid. Misdiagnosis or delay in PCNSL diagnosis because of atypical features in disease presentation and radiographic findings could lead to PCNSL progression and worsening neurological deficits.
PubMed: 37522053
DOI: 10.3892/etm.2023.12109 -
Frontiers in Endocrinology 2023The diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The diversity of clinical trajectories in diabetic kidney disease (DKD) has made blood and biochemical urine markers less precise, while renal puncture, the gold standard, is almost impossible in the assessment of diabetic kidney disease, and the value of functional magnetic resonance imaging in the evaluation of diabetic pathological alterations is increasingly recognized.
METHODS
The literature on functional magnetic resonance imaging (fMRI) for the assessment of renal alterations in diabetic kidney disease was searched in PubMed, Web of Science, Cochrane Library, and Embase databases. The search time limit is from database creation to March 10, 2023. RevMan was used to perform a meta-analysis of the main parameters of fMRIs extracted from DKD patients and healthy volunteers (HV).
RESULTS
24 publications (1550 subjects) were included in this study, using five functional MRIs with seven different parameters. The renal blood flow (RBF) values on Arterial spin labeling magnetic resonance imaging (ASL-MRI) was significantly lower in the DKD group than in the HV group. The [WMD=-99.03, 95% CI (-135.8,-62.27), <0.00001]; Diffusion tensor imaging magnetic resonance imaging (DTI-MRI) showed that the fractional anisotropy (FA) values in the DKD group were significantly lower than that in HV group [WMD=-0.02, 95%CI (-0.03,-0.01), <0.0001]. And there were no statistically significant differences in the relevant parameters in Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) or Intro-voxel incoherent movement magnetic resonance imaging (IVIM-DWI).
DISCUSSION
ASL and DWI can identify the differences between DKD and HV. DTI has a significant advantage in assessing renal cortical changes; IVIM has some value in determining early diabetic kidney disease from the cortex or medulla. We recommend combining multiple fMRI parameters to assess structural or functional changes in the kidney to make the assessment more comprehensive. We did not observe a significant risk of bias in the present study.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk, identifier CRD42023409249.
Topics: Magnetic Resonance Imaging; Diabetic Neuropathies; Diffusion Tensor Imaging; Kidney; Diabetes Mellitus
PubMed: 37484949
DOI: 10.3389/fendo.2023.1226830 -
Nature Communications Jul 2023Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal...
Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.
Topics: Humans; Kidney Medulla; Matrix Metalloproteinase 9; Matrix Metalloproteinase 7; Calcium Oxalate; Transcriptome; Kidney Calculi
PubMed: 37468493
DOI: 10.1038/s41467-023-38975-8 -
PloS One 2023Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose...
Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose lipopolysaccharide (LPS) was investigated in this work to induce rapid and stable proteinuria in hyperglycemic rats and the underlying mechanism was studied. Hyperglycemia rats was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21 days, the model rats received a subinjury dose of 0.8 mg / kg LPS intraperitoneally (i.p.). We detected related biochemical indexes at different time periods after LPS injection and examined the expression of glomerular podocyte-associated proteins. Simultaneously, we measured expression of inflammatory factors, apoptotic proteins and albumin (ALB) in the renal cortex and renal medulla, respectively. PAS (Periodic Acid Schiff) staining was used to observe renal pathology. After LPS injection, urinary microalbumin (umALB) increased significantly and lasted longer. The expression of Nephrin, Podocin and necroptosis factor kappa B (NF-κB) in rennal cortex and Interleukin 18 (IL-18), Caspase-1, NF-κB and ALB in the renal medulla was significantly changed. Pathologically, the glomerular basement membrane was observed to be significantly thickened, the renal tubules were dilated, and the epithelial cells fell off in a circle. LPS promoted the continuous increase in urinary microalbumin in hyperglycemic rats, which was related to the damage to the glomerular basement membrane and renal tubular epithelial cells and to the inflammatory reaction in the kidney involved in NF-κB signaling, and this pathological damage can help to establish a stable model of diabetic nephropathy with increased proteinuria.
Topics: Rats; Animals; Diabetic Nephropathies; Lipopolysaccharides; NF-kappa B; Kidney; Proteinuria
PubMed: 37467292
DOI: 10.1371/journal.pone.0288876 -
Nephrology, Dialysis, Transplantation :... Jan 2024The use of cyclosporin A (CsA) is hampered by the development of nephrotoxicity including hypertension, which is partially dependent on renal sodium retention. To...
BACKGROUND
The use of cyclosporin A (CsA) is hampered by the development of nephrotoxicity including hypertension, which is partially dependent on renal sodium retention. To address this issue, we have investigated in vivo sodium reabsorption in different nephron segments of CsA-treated rats through micropuncture study coupled to expression analyses of sodium transporters. To translate the findings in rats to human, kidney-transplanted patients having CsA treatment were enrolled in the study.
METHODS
Adult male Sprague-Dawley rats were treated with CsA (15 mg/kg/day) for 21 days, followed by micropuncture study and expression analyses of sodium transporters. CsA-treated kidney-transplanted patients with resistant hypertension were challenged with 50 mg furosemide.
RESULTS
CsA-treated rats developed hypertension associated with reduced glomerular filtration rate. In vivo microperfusion study demonstrated a significant decrease in rate of absolute fluid reabsorption in the proximal tubule but enhanced sodium reabsorption in the thick ascending limb of Henle's loop (TAL). Expression analyses of sodium transporters at the same nephron segments further revealed a reduction in Na+-H+ exchanger isoform 3 (NHE3) in the renal cortex, while TAL-specific, furosemide-sensitive Na+-K+-2Cl- cotransporter (NKCC2) and NHE3 were significantly upregulated in the inner stripe of outer medulla. CsA-treated patients had a larger excretion of urinary NKCC2 protein at basal condition, and higher diuretic response to furosemide, showing increased FeNa+, FeCl- and FeCa2+ compared with both healthy controls and FK506-treated transplanted patients.
CONCLUSION
Altogether, these findings suggest that up-regulation of NKCC2 along the TAL facilitates sodium retention and contributes to the development of CsA-induced hypertension.
Topics: Adult; Humans; Male; Rats; Animals; Cyclosporine; Sodium-Hydrogen Exchanger 3; Up-Regulation; Furosemide; Rats, Sprague-Dawley; Hypertension; Sodium; Solute Carrier Family 12, Member 1
PubMed: 37463050
DOI: 10.1093/ndt/gfad161 -
Renal Failure Dec 2023The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes...
INTRODUCTION
The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients.
METHODS
Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis.
RESULTS
A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively).
CONCLUSION
The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.
Topics: Male; Humans; Middle Aged; Female; Kidney Transplantation; Elasticity Imaging Techniques; Prognosis; Kidney; Kidney Diseases
PubMed: 37462113
DOI: 10.1080/0886022X.2023.2235015 -
Advances in Physiology Education Sep 2023Countercurrent multiplication (CCM) is widely accepted as the mechanism for the generation of the corticopapillary osmotic gradient in the outer medulla of mammalian...
Countercurrent multiplication (CCM) is widely accepted as the mechanism for the generation of the corticopapillary osmotic gradient in the outer medulla of mammalian kidneys. However, several issues in the literature cause the current explanations of CCM to be inefficient and incomplete. As a result, it is challenging to clearly explain CCM in physiology education. The goal of this article is to share a modified version of CCM with more understandable explanation in the hopes of motivating peer discussion, further improvement, and future research. To reach this goal, the logical processes leading to CCM are first analyzed, which results in a set of formulas that serve as the principles governing CCM. Next, the cessation of CCM is addressed to provide a complete picture of the modified version of CCM. Throughout these two steps, the issues mentioned above are identified and addressed so that how the modified version of CCM eliminates these issues becomes clear. The formulas mentioned above are provided in the Tables S1, S2, and S3 (all Supplemental material is available in the Supplemental Excel File at https://doi.org/10.6084/m9.figshare.23515614) to explain how the interstitial and intrathick ascending limb osmotic concentration (OC) values used in the figures in this article are simulated and how alternative OC values can be generated from Tables S1 and S2 to illustrate CCM. Countercurrent multiplication is widely accepted as the mechanism for the generation of the corticopapillary osmotic gradient in the outer medulla of mammalian kidneys, but the current explanations of it in textbooks and the literature are inefficient and incomplete, leading to confusion for students. This article shares a modified version of countercurrent multiplication with more understandable explanation as a way of motivating peer discussion, further improvement, and future research.
Topics: Animals; Humans; Kidney Medulla; Kidney; Osmosis; Mammals
PubMed: 37439318
DOI: 10.1152/advan.00227.2022