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Kidney International Feb 2024The kidney medulla is a specialized region with important homeostatic functions. It has been implicated in genetic and developmental disorders along with ischemic and...
The kidney medulla is a specialized region with important homeostatic functions. It has been implicated in genetic and developmental disorders along with ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla's baseline gene expression and epigenomic signatures have not been well described in the adult human kidney. Here we generated and analyzed gene expression (RNA-seq), chromatin accessibility (ATAC-seq), chromatin conformation (Hi-C) and spatial transcriptomic data from the adult human kidney cortex and medulla. Tissue samples were obtained from macroscopically dissected cortex and medulla of tumor-adjacent normal material in nephrectomy specimens from five male patients. We used these carefully annotated specimens to reassign incorrectly labeled samples in the larger public Genotype-Tissue Expression (GTEx) Project, and to extract meaningful medullary gene expression signatures. Using integrated analysis of gene expression, chromatin accessibility and conformation profiles, we found insights into medulla development and function and then validated this by spatial transcriptomics and immunohistochemistry. Thus, our datasets provide a valuable resource for functional annotation of variants from genome-wide association studies and are freely accessible through an epigenome browser portal.
Topics: Adult; Humans; Male; Multiomics; Genome-Wide Association Study; Chromatin; Kidney; Transcriptome
PubMed: 37995909
DOI: 10.1016/j.kint.2023.10.024 -
Abdominal Radiology (New York) Jan 2022Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the...
BACKGROUND
Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients.
METHODS
Thirty-four patients with glomerular filtration rate (GFR) over 20 ml/min/1.73m had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity.
RESULTS
Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min-max: 0%-100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%-50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P < 0.05 for whole kidney and medulla MRE-derived stiffness).
CONCLUSION
MRE-derived stiffness values were lower in patients with chronic injury. Stiffness decreases as glomerulosclerosis and tubulointerstitial fibrosis progresses in patients with primary glomerulonephritis and AA amyloidosis. With future studies, there may be a role for MRE to assess renal function in concert with conventional markers.
Topics: Amyloidosis; Elasticity Imaging Techniques; Fibrosis; Glomerulonephritis; Humans; Liver Cirrhosis; Magnetic Resonance Imaging; Serum Amyloid A Protein
PubMed: 34633496
DOI: 10.1007/s00261-021-03296-1 -
Journal of Magnetic Resonance Imaging :... Jul 2023Renal diffusion-weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM),...
BACKGROUND
Renal diffusion-weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and hybrid models. A better understanding of their contrast may increase specificity.
PURPOSE
To measure modulation of DWI with cardiac phase and flow-compensated (FC) diffusion gradient waveforms.
STUDY TYPE
Prospective.
POPULATION
Six healthy volunteers (ages: 22-48 years, five females), water phantom.
FIELD STRENGTH/SEQUENCE
3-T, prototype DWI sequence with 2D echo-planar imaging, and bipolar (BP) or FC gradients. 2D Half-Fourier Single-shot Turbo-spin-Echo (HASTE). Multiple-phase 2D spoiled gradient-echo phase contrast (PC) MRI.
ASSESSMENT
BP and FC water signal decays were qualitatively compared. Renal arteries and velocities were visualized on PC-MRI. Systolic (peak velocity), diastolic (end stable velocity), and pre-systolic (before peak velocity) phases were identified. Following mutual information-based retrospective self-registration of DWI within each kidney, and Marchenko-Pastur Principal Component Analysis (MPPCA) denoising, combined IVIM-DTI analysis estimated mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues (λi) from tissue diffusivity (D ), perfusion fraction (f ), and pseudodiffusivity (D , D , D ), for each tissue (cortex/medulla, segmented on b0/FA respectively), phase, and waveform (BP, FC). Monte Carlo water diffusion simulations aided data interpretation.
STATISTICAL TESTS
Mixed model regression probed differences between tissue types and pulse sequences. Univariate general linear model analysis probed variations among cardiac phases. Spearman correlations were measured between diffusion metrics and renal artery velocities. Statistical significance level was set at P < 0.05.
RESULTS
Water BP and FC signal decays showed no differences. Significant pulse sequence dependence occurred for λ , λ , FA, D , f , D , D in cortex and medulla, and medullary λ . Significant cortex/medulla differences occurred with BP for all metrics except MD (systole [P = 0.224]; diastole [P = 0.556]). Significant phase dependence occurred for D , D , D for BP and medullary λ , λ , λ , MD for FC. FA correlated significantly with velocity. Monte Carlo simulations indicated medullary measurements were consistent with a 34 μm tubule diameter.
DATA CONCLUSION
Cardiac gating and flow compensation modulate of measurements of renal diffusion.
EVIDENCE LEVEL
2 TECHNICAL EFFICACY STAGE: 2.
Topics: Female; Humans; Young Adult; Adult; Middle Aged; Diffusion Tensor Imaging; Anisotropy; Prospective Studies; Retrospective Studies; Kidney; Diffusion Magnetic Resonance Imaging; Motion; Water
PubMed: 36399101
DOI: 10.1002/jmri.28517 -
Nephrology (Carlton, Vic.) Sep 2022Real-time ultrasound-guided renal biopsy is generally applied to diagnose multiple kidney diseases. A practical simulation model is desired since it is an invasive...
Real-time ultrasound-guided renal biopsy is generally applied to diagnose multiple kidney diseases. A practical simulation model is desired since it is an invasive technique with higher risks of complications such as bleeding. We developed a simple simulation tool for ultrasound-guided renal biopsy using boiled eggs. Boiled chicken eggs were embedded in the agar, and a biopsy simulation was performed using a real-time ultrasound-guided technique as the renal biopsy simulator by trainees and biopsy-proficient nephrologists, and the feedback from the participants was obtained. The ultrasonographic evaluation revealed a clear contrast between egg yolk and white, which clearly mimicked the kidney cortex and medulla region. In addition, we observed the needle entering the egg white under needle penetration, and we obtained the biopsy core consisting of egg white. As for the simulations, all the participants succeeded in obtaining the appropriate samples. A total of 92% of the trainees agreed that the simulation could reduce their fears of performing renal biopsies in patients. In addition, all the trainees and biopsy-proficient nephrologists recommend using the simulator for trainees before conducting renal biopsies on patients. The total cost of the simulator was low (
renal biopsy. Topics: Biopsy; Humans; Image-Guided Biopsy; Kidney; Kidney Diseases; Ultrasonography; Ultrasonography, Interventional
PubMed: 35762140
DOI: 10.1111/nep.14079 -
Journal of Ultrasound in Medicine :... Jun 2023The objective of our study was to assess the ability of contrast-enhanced ultrasound (CEUS) in evaluating renal microperfusion in an animal model.
OBJECTIVES
The objective of our study was to assess the ability of contrast-enhanced ultrasound (CEUS) in evaluating renal microperfusion in an animal model.
METHODS
Twenty Sprague-Dawley rats were subdivided into two groups: the normal and chronic intermittent hypoxia (CIH) groups. In the CIH model, 10 Sprague-Dawley rats were exposed to CIH for 8 weeks to mimic obstructive sleep apnea (OSA). The CEUS parameters of the renal cortex and medulla were obtained and compared between groups. The pathological changes of the kidney tissues were examined by histological staining such as hematoxylin and eosin (H&E) and Masson's trichrome.
RESULTS
CIH caused morphological damage to kidneys. In the cortex, the peak intensity (PI) (P = .009) was significantly lower and time to peak (Ttop) (P = .019) was significantly prolonged in the CIH group compared with the controls. The area under ascending curve (WiAUC) in the medulla and cortex were both significantly lower in the CIH group than those in the control group (P both <.05). CEUS parameters (including PI and WiAUC of the cortex and WiAUC of the medulla) were negatively correlated with serum creatinine (P all <.05). In the medulla, the area under descending curve (WoAUC) was positively correlated with serum creatinine (P = .027), PI was negatively correlated with uric acid (P = .034).
CONCLUSION
CEUS parameters (including Ttop, PI, WoAUC, and WiAUC) reflect renal microvascular changes in CIH. CEUS could be a safe and accurate imaging method to assess renal microvascular damage in CIH rats.
Topics: Rats; Animals; Rats, Sprague-Dawley; Creatinine; Kidney; Hypoxia; Ultrasonography; Disease Models, Animal
PubMed: 36478449
DOI: 10.1002/jum.16147 -
Clinical and Experimental Hypertension... Jan 2022This study was conducted to explore the effect of renal denervation (RDN) on the renin-angiotensin-aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs)....
This study was conducted to explore the effect of renal denervation (RDN) on the renin-angiotensin-aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs). Our experimental rats were randomly divided into the RDN group conducted by painting 10% phenol on the bilateral renal nerves (RDNX), the shamoperation group simply painting with saline (Sham), and the normotension control group (WKY) following all the animal blood and tissues of kidney, hypothalamus, and adrenal gland collected and examined 2 weeks after RDN operation. We found that the aldosterone (ALD) levels in serum and tissues all decreased in the RDNX group compared with the Sham group ( < .05). Meantime, the expression of angiotensin II type1 receptor (AT1R) mRNA also exhibited significantly reduced by 2.22-fold in the RDNX group compared to the Sham group identical to the expression of AT1R protein in the renal cortex and outer stripe of the outer medulla (OSOM) subjected to denervation surgery, which manifested the lower ATIR protein expression than the Sham group ( < .05). Besides, the expression of angiotensin II (Ang II) protein in the cortex , OSOM, and inner stripe of the outer medulla were all attenuated by RDN in comparison with the Sham group ( < .05). RDN reduced intrarenal RAAS and circulating RAAS to lower blood pressure and repair renal function.
Topics: Angiotensin II; Animals; Blood Pressure; Denervation; Hypertension; Kidney; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin-Angiotensin System
PubMed: 34818958
DOI: 10.1080/10641963.2021.1996587 -
Clinical Kidney Journal Aug 2021Acute kidney injury (AKI) is associated with a marked increase in mortality as well as subsequent chronic kidney disease (CKD) and end-stage kidney disease. We performed...
BACKGROUND
Acute kidney injury (AKI) is associated with a marked increase in mortality as well as subsequent chronic kidney disease (CKD) and end-stage kidney disease. We performed multiparametric magnetic resonance imaging (MRI) with the aim of identifying potential non-invasive MRI markers of renal pathophysiology in AKI and during recovery.
METHODS
Nine participants underwent inpatient MRI scans at time of AKI; seven had follow-up scans at 3 months and 1 year following AKI. Multiparametric renal MRI assessed total kidney volume (TKV), renal perfusion using arterial spin labelling, T mapping and blood oxygen level-dependent (BOLD) R* mapping.
RESULTS
Serum creatinine concentration had recovered to baseline levels at 1-year post-AKI in all participants. At the time of AKI, participants had increased TKV, increased cortex/medulla T and reduced cortical perfusion compared with the expected ranges in healthy volunteers and people with CKD. TKV and T values decreased over time after AKI and returned to expected values in most but not all patients by 1 year. Cortical perfusion improved to a lesser extent and remained below the expected range in the majority of patients by 1-year post-AKI. BOLD R* data showed a non-significant trend to increase over time post-AKI.
CONCLUSIONS
We observed a substantial increase in TKV and T during AKI and a marked decrease in cortical perfusion. Despite biochemical recovery at 1-year post-AKI, MRI measures indicated persisting abnormalities in some patients. We propose that such patients may be more likely to have further AKI episodes or progress to CKD and further longitudinal studies are required to investigate this. .
PubMed: 34345421
DOI: 10.1093/ckj/sfaa221 -
BMC Urology Nov 2021Nephrocalcinosis is often asymptomatic but can manifest with renal colic or hematuria. There is no reported association between nephrocalcinosis and renal vascular...
BACKGROUND
Nephrocalcinosis is often asymptomatic but can manifest with renal colic or hematuria. There is no reported association between nephrocalcinosis and renal vascular malformations, which may also be a source of hematuria. We herein present a case of a patient with hematuria related to nephrocalcinosis and renal papillary varicosities. These varicosities were diagnosed and successfully treated with flexible ureteroscopy and laser fulguration.
CASE PRESENTATION
A 24-year-old female with a history of epilepsy (on zonisamide), recent uncomplicated pregnancy, and new diagnosis of nephrocalcinosis presented with right flank pain and intermittent gross hematuria. Imaging revealed intermittent right sided hydronephrosis. A cystoscopy identified hematuria from the right ureteral orifice. Diagnostic flexible ureteroscopy revealed numerous intrapapillary renal stones and varicose veins of several renal papillae. A 200 μm holmium laser fiber was used to unroof these stones and fulgurate the varicosities with resolution of her symptoms for several months. She later presented with left-sided symptoms and underwent left ureteroscopy with similar findings and identical successful treatment.
CONCLUSION
Unilateral hematuria from discrete vascular lesions of the renal collecting system may be obscured by other benign co-existing conditions, such as nephrocalcinosis and nephrolithiasis. Although a simultaneous presentation is rare, flexible ureteroscopy with laser fulguration offers an ideal diagnostic and therapeutic modality for these concurrent conditions if symptoms arise.
Topics: Female; Hematuria; Humans; Kidney Calculi; Kidney Medulla; Laser Coagulation; Nephrocalcinosis; Ureteroscopy; Varicose Veins; Young Adult
PubMed: 34844581
DOI: 10.1186/s12894-021-00931-3 -
Journal of Cellular and Molecular... Apr 2024Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due... (Review)
Review
Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi-step and long-term process involving the transformation of stone-forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.
Topics: Humans; Kidney Medulla; Kidney Calculi; Calcinosis; Endoscopy; Inflammation
PubMed: 38509735
DOI: 10.1111/jcmm.18235 -
Pediatric Nephrology (Berlin, Germany) Sep 2019In recent years, progress has been made on understanding the relationship between vesicoureteral reflux (VUR) and urinary tract infection (UTI). The findings on recent... (Review)
Review
In recent years, progress has been made on understanding the relationship between vesicoureteral reflux (VUR) and urinary tract infection (UTI). The findings on recent prospective, randomized, controlled studies have questioned the conventional VUR clinical significance and, therefore, have challenged the traditional diagnostic and therapeutic recommendations. These new studies have redefined the pathogenic role of vesicoureteral reflux in UTI as well as have disputed the routine use of urinary antibiotic prophylaxis to prevent UTI and renal damage in VUR patients. The time to overinvestigate and treat the vast majority of otherwise healthy children who have an uncomplicated UTI with long-term antibiotic prophylaxis seems to be over. Is there a role of severe VUR in the development of chronic renal disease and renal failure? New ideas are needed to answer these questions with the goal to avoid repeating past mistakes when therapeutic choices were based on expert opinions rather than facts.
Topics: Antibiotic Prophylaxis; Child; Cystography; Evidence-Based Medicine; Humans; Kidney Cortex; Kidney Medulla; Nephrology; Practice Guidelines as Topic; Prevalence; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Treatment Outcome; Ureter; Urinary Bladder; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 30132079
DOI: 10.1007/s00467-018-4045-9