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1
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Caster DJ, Abner CW, Walker PD, Wang K, Heo J, Rava AR, Bunke M. Clinicopathological Characteristics of Adult IgA Nephropathy in the United States. Kidney Int Rep 2023; 8:1792-1800. [PMID: 37705898 PMCID: PMC10496075 DOI: 10.1016/j.ekir.2023.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 09/15/2023] Open
Abstract
Introduction IgA nephropathy (IgAN) is a progressive autoimmune kidney disease and a leading cause of glomerular disease that can result in kidney failure (KF). The median age at diagnosis is 35 to 37 years and approximately 50% of patients will progress to KF within 20 years. We aimed to enhance the understanding of renal histology and chronic kidney disease (CKD) stage at the time of IgAN diagnosis using a large real-world biopsy cohort. Methods This retrospective cohort study evaluated biopsy data and clinical characteristics from adult patients within the US who were diagnosed with IgAN between January 1, 2016 to May 31, 2020. Descriptive statistics were summarized and relationship(s) between each Oxford Classification (MEST-C) component score with 24-hour proteinuria or CKD stage were examined using regression analysis. Results A total of 4375 patients (mean age 47.7 years, 62.7% male) met eligibility criteria. Mild to moderate mesangial hypercellularity (47.3%), segmental sclerosis (65.0%), tubular atrophy ≥25% (57.4%), and crescents (18.5%) were identified; and 74.6% of patients were at CKD stage ≥3. Proteinuria ≥1 g/d was associated with higher MEST-C scores, and the odds of mesangial hypercellularity, segmental sclerosis, tubular atrophy, and crescents increased with CKD stage. Conclusion Most patients with IgAN in our US cohort were diagnosed at CKD stage ≥3 and had high MEST-C scores and proteinuria that are suggestive of significant disease burden at the time of kidney biopsy. Strategies are required to raise awareness and promote earlier detection of asymptomatic urinary abnormalities before extensive irreversible kidney damage has occurred.
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Affiliation(s)
| | | | | | - Kaijun Wang
- Travere Therapeutics, Inc., San Diego, California, USA
| | | | | | - Martin Bunke
- Travere Therapeutics, Inc., San Diego, California, USA
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2
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Zhou C, Zhang Q, Lu L, Wang J, Liu D, Liu Z. Metabolomic Profiling of Amino Acids in Human Plasma Distinguishes Diabetic Kidney Disease From Type 2 Diabetes Mellitus. Front Med (Lausanne) 2021; 8:765873. [PMID: 34912824 PMCID: PMC8666657 DOI: 10.3389/fmed.2021.765873] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/01/2021] [Indexed: 01/02/2023] Open
Abstract
Background: Diabetic kidney disease (DKD) is a highly prevalent complication in patients with type 2 diabetes mellitus (T2DM). Patients with DKD exhibit changes in plasma levels of amino acids (AAs) due to insulin resistance, reduced protein intake, and impaired renal transport of AAs. The role of AAs in distinguishing DKD from T2DM and healthy controls has yet to be elucidated. This study aimed to investigate the metabolomic profiling of AAs in the plasma of patients with DKD. Methods: We established an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to detect the plasma levels of the 20 AAs in healthy controls (n = 112), patients with T2DM (n = 101), and patients with DKD (n = 101). The key AAs associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) models with loading plots, shared and unique structures (SUS) plots, and variable importance in projection (VIP) values. The discrimination accuracies of these key AAs were then determined by analyses of receiver-operating characteristic (ROC) curves. Results: Metabolomic profiling of plasma revealed significant alterations in levels of the 20 AAs in patients with DKD when compared to those in either patients with T2DM or healthy controls. Metabolomic profiling of the 20 AAs showed a visual separation of patients with DKD from patients with T2DM and healthy controls in OPLS-DA models. Based on loading plots, SUS plots, and VIP values in the OPLS-DA models, we identified valine and cysteine as potential contributors to the progression of DKD from patients with T2DM. Histidine was identified as a key mediator that could distinguish patients with DKD from healthy controls. Plasma levels of histidine and valine were decreased significantly in patients with DKD with a decline in kidney function, and had excellent performance in distinguishing patients with DKD from patients with T2DM and healthy controls according to ROC curves. Conclusion: Plasma levels of histidine and valine were identified as the main AAs that can distinguish patients with DKD. Our findings provide new options for the prevention, treatment, and management of DKD.
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Affiliation(s)
- Chunyu Zhou
- Blood Purification Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China
| | - Qing Zhang
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China.,Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liqian Lu
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China.,Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiao Wang
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China.,Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dongwei Liu
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China.,Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, China
| | - Zhangsuo Liu
- Blood Purification Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, China.,Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, China
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3
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Sousanieh G, Whittier WL, Rodby RA, Peev V, Korbet SM. Percutaneous Renal Biopsy Using an 18-Gauge Automated Needle Is Not Optimal. Am J Nephrol 2021; 51:982-987. [PMID: 33454708 DOI: 10.1159/000512902] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 11/06/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND As percutaneous renal biopsies (PRBs) are increasingly performed by radiologists, an increase in the use of 18-gauge automated needle stands to compromise adequacy. We compare the adequacy and safety of PRB with 14-, 16-, and 18-gauge automated needles. METHODS PRB of native (N-592) and transplant (T-1,023) kidneys was performed from January 2002 to December 2019 using real-time ultrasound. Baseline clinical and laboratory data, biopsy data (number of cores, total glomeruli, and total glomeruli per core), and outcome (hematoma on renal US at 1-h, complications, and transfusion) were collected prospectively. PRB with N14g (337) versus N16g (255) and T16g (892) versus T18g (131) needles were compared. A p value of <0.05 was significant. RESULTS PRB with an 18-g needle yielded the lowest number of total glomeruli per biopsy (N14g vs. N16g: 33 ± 13 vs. 29 ± 12, p < 0.01 and T16g vs. T18g: 34 ± 16 vs. 21 ± 11, p < 0.0001), significantly fewer total glomeruli per core (T16g vs. T18g: 12.7 ± 6.4 vs. 9.6 ± 5.0, p < 0.001 and N16g vs. T18g: 14.2 ± 6.3 vs. 9.6 ± 5.0, p < 0.001). A hematoma by renal US 1-h post-PRB was similar for native (14g-35% vs. 16g-29%, p = 0.2), and transplant biopsies (16g-10% vs. 18g-9%, p = 0.9) and the complication rate for native (14g-8.9% vs. 16g-7.1%, p = 0.5), transplant biopsies (16g-4.6% vs. 18g-1.5%, p = 0.2) and transfusion rate for native (14g-7.7% vs. 16g-5.8%, p = 0.4), and transplant biopsies (16g-3.8% vs. 18g-0.8%, p = 0.1) were similar irrespective of needle size. CONCLUSIONS PRB of native and transplant kidneys with the use of a 16-gauge needle provides an optimal sample. However, our experience in transplant biopsies suggests the use of an 18-gauge needle stands to jeopardize the diagnostic accuracy of the PRB while not improving safety.
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Affiliation(s)
- George Sousanieh
- Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - William L Whittier
- Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Roger A Rodby
- Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Vasil Peev
- Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Stephen M Korbet
- Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA,
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4
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Esteve E, Luque Y, Waeytens J, Bazin D, Mesnard L, Jouanneau C, Ronco P, Dazzi A, Daudon M, Deniset-Besseau A. Nanometric Chemical Speciation of Abnormal Deposits in Kidney Biopsy: Infrared-Nanospectroscopy Reveals Heterogeneities within Vancomycin Casts. Anal Chem 2020; 92:7388-7392. [PMID: 32406230 DOI: 10.1021/acs.analchem.0c00290] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Infrared (IR) spectromicroscopy allows chemical mapping of a kidney biopsy. It is particularly interesting for chemical speciation of abnormal tubular deposits and calcification. In 2017, using IR spectromicroscopy, we described a new entity called vancomycin cast nephropathy. However, despite recent progresses, the IR microspectrometer spatial resolution is intrinsically limited by diffraction (a few micrometers). Combining atomic force microscopy and IR lasers (AFMIR) allows acquisition of infrared absorption spectra with a resolution and sensitivity in between 10 and 100 nm. Here we show that AFMIR can be used on standard paraffin embedded kidney biopsies. Vancomycin cast could be identified in a damaged tubule. Interestingly unlike standard IR spectromicroscopy, AFMIR revealed heterogeneity of the deposits and established that vancomycin coprecipitated with phosphate containing molecules. These findings highlight the high potential of this approach with nanometric spatial resolution which opens new perspectives for studies on drug-induced nephritis, nanocrystals, and local lipid or carbohydrates alterations.
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Affiliation(s)
- Emmanuel Esteve
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France.,Nephrology and Dialysis Department, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
| | - Yosu Luque
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France.,Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
| | - Jehan Waeytens
- Université Paris-Saclay, CNRS, Institut de Chimie Physique, UMR 8000, 91405 Orsay, France.,Structure et Fonction des Membranes Biologiques, Faculté des Sciences, Université Libre de Bruxelles (ULB), CP 206/02, Boulevard du Triomphe, B-1050 Bruxelles, Belgium
| | - Dominique Bazin
- Université Paris-Saclay, CNRS, Institut de Chimie Physique, UMR 8000, 91405 Orsay, France
| | - Laurent Mesnard
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France.,Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
| | - Chantal Jouanneau
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France
| | - Pierre Ronco
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France.,Nephrology and Dialysis Department, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
| | - Alexandre Dazzi
- Université Paris-Saclay, CNRS, Institut de Chimie Physique, UMR 8000, 91405 Orsay, France
| | - Michel Daudon
- Sorbonne Université, UPMC Paris 06, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, F-75020 Paris, France.,Explorations Fonctionnelles Multidisciplinaires, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
| | - Ariane Deniset-Besseau
- Université Paris-Saclay, CNRS, Institut de Chimie Physique, UMR 8000, 91405 Orsay, France
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5
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Winfree S, Dagher PC, Dunn KW, Eadon MT, Ferkowicz M, Barwinska D, Kelly KJ, Sutton TA, El-Achkar TM. Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease. Nephron Clin Pract 2018; 140:134-139. [PMID: 29870980 DOI: 10.1159/000490006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 05/12/2018] [Indexed: 12/15/2022] Open
Abstract
Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease.
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Affiliation(s)
- Seth Winfree
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Department of Integrative and Cellular Physiology, Indiana University, Indianapolis, Indiana, USA
| | - Pierre C Dagher
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Department of Integrative and Cellular Physiology, Indiana University, Indianapolis, Indiana, USA.,Indianapolis VA Medical Center, Indianapolis, Indiana, USA
| | - Kenneth W Dunn
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Michael T Eadon
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Michael Ferkowicz
- Department of Surgery, Indiana University, Indianapolis, Indiana, USA
| | - Daria Barwinska
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Katherine J Kelly
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Timothy A Sutton
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Tarek M El-Achkar
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Department of Integrative and Cellular Physiology, Indiana University, Indianapolis, Indiana, USA.,Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Indianapolis VA Medical Center, Indianapolis, Indiana, USA
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6
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Visconti L, Cernaro V, Ricciardi CA, Lacava V, Pellicanò V, Lacquaniti A, Buemi M, Santoro D. Renal biopsy: Still a landmark for the nephrologist. World J Nephrol 2016; 5:321-327. [PMID: 27458561 PMCID: PMC4936339 DOI: 10.5527/wjn.v5.i4.321] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Revised: 03/14/2016] [Accepted: 04/06/2016] [Indexed: 02/06/2023] Open
Abstract
Renal biopsy was performed for the first time more than one century ago, but its clinical use was routinely introduced in the 1950s. It is still an essential tool for diagnosis and choice of treatment of several primary or secondary kidney diseases. Moreover, it may help to know the expected time of end stage renal disease. The indications are represented by nephritic and/or nephrotic syndrome and rapidly progressive acute renal failure of unknown origin. Nowadays, it is performed mainly by nephrologists and radiologists using a 14-18 gauges needle with automated spring-loaded biopsy device, under real-time ultrasound guidance. Bleeding is the major primary complication that in rare cases may lead to retroperitoneal haemorrhage and need for surgical intervention and/or death. For this reason, careful evaluation of risks and benefits must be taken into account, and all procedures to minimize the risk of complications must be observed. After biopsy, an observation time of 12-24 h is necessary, whilst a prolonged observation may be needed rarely. In some cases it could be safer to use different techniques to reduce the risk of complications, such as laparoscopic or transjugular renal biopsy in patients with coagulopathy or alternative approaches in obese patients. Despite progress in medicine over the years with the introduction of more advanced molecular biology techniques, renal biopsy is still an irreplaceable tool for nephrologists.
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