Nephrology and the Percutaneous Renal Biopsy

Korbet, Stephen M.

doi:10.2215/cjn.08290812

Cited by 47 publications

(60 citation statements)

References 34 publications

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“…We found that FSGS-linked ACTN4 mutants significantly reduced GRE reporter activity (Fig. 5A, lanes [3][4][5], and the reduction of GRE activities was also observed in GR-overexpressing cells (Fig. 5A, lanes 8 -10).…”

Section: Expression Of Gr␣ In Immortalized Hpcs and Primarymentioning

confidence: 67%

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes

Zhao

Khurana

Charkraborty

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangGlucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that ␣ actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-B (p65) binding sites on GR-transrepressed promoters such as IL-1␤, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes.

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Section: Expression Of Gr␣ In Immortalized Hpcs and Primarymentioning

confidence: 67%

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes

Zhao

Khurana

Charkraborty

et al. 2017

Journal of Biological Chemistry

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“…Since the introduction of automated needles, there has been a tendency to use the smaller 16- or 18-gauge needles rather than 14-gauge needles, which had been the common practice with manual needles [3,12]. The rationale for this is not clear but may be linked to the increasing number of biopsies being performed by radiologists, who are more likely to use an 18-gauge needle [21,30,33]. In the Norwegian Kidney Biopsy Registry report [21] of 9,288 biopsies, in which 54% of biopsies were performed by radiologists, an 18-gauge automated needle was used in 57% of biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…Differences in complication rates among studies can vary substantially and can be difficult to interpret because of confounding issues such as the nature of the study (retrospective vs. prospective), patient mix, the type of imaging used, the needle type or gauge used, as well as who is performing the biopsy [3,7,12,14,20,23,25,26,27,28,29,30]. To further enhance our understanding of the success and complications associated with the PRB of native kidneys, we present one of the largest, prospective, single-center experiences with PRB performed in adults at an academic institution using real-time ultrasound and 14-gauge needles.…”

Section: Introductionmentioning

confidence: 99%

Percutaneous Renal Biopsy of Native Kidneys: A Single-Center Experience of 1,055 Biopsies

Korbet

Volpini

Whittier³

2014

Am J Nephrol

Self Cite

132

118

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Background: Percutaneous renal biopsy (PRB) of native kidneys is an essential tool in the diagnosis and management of renal disease. We report one of the largest single-center experiences on the success and safety of the procedure. Methods: From June 1983 to March 2012, 1,055 adults underwent PRB using real-time ultrasound guidance and 14-gauge biopsy needles. Data were collected prospectively for 826 biopsies (78%). Statistical analysis was performed using the Mann-Whitney test, Wilcoxon matched pairs test and Kruskal-Wallis test for continuous data or the Fisher's exact test and χ² test for categorical data. Multivariate analysis using logistic regression was performed to determine which feature at baseline was predictive of a complication following renal biopsy. Results: Patients were aged 46 ± 17 years; 38% were male, 40% were white and 43% were African-American. Serum creatinine (SCr) was 2.3 ± 2.3 mg/dl (>1.5 mg/dl in 47%). The pre-PRB hemoglobin was 12 ± 2 g/dl (<11.0 g/dl in 35%). Adequate tissue for diagnosis was obtained in 99% of biopsies. Minor complications occurred in 8.1% of biopsies (mainly gross hematuria, in 4.5%). Major complications occurred in 6.6% of biopsies, with transfusions required in 5.3%. Only 1 death (0.09%) resulted from post-PRB bleeding. By multivariate analysis, baseline features predictive of a complication were systolic blood pressure >170 mm Hg (OR 4.2, 95% CI 1.8-9.8), bleeding time >7.5 min (OR 1.7, CI 1.2-2.5) and SCr >3.5 mg/dl (OR 1.8, CI 1.2-2.9). Conclusions: PRB of native kidneys using real-time ultrasound with a 14-gauge automated needle remains a successful and safe procedure.

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“…It is a matter of ongoing debate as to whether nephrology fellowship programs should be required to provide sufficient training for graduates to independently and safely perform PRBs (79). Some of the reasons cited for eliminating this requirement include time constraints, malpractice insurance costs, nephrologists do not do biopsies in practice, and inability to provide sufficient supervised experience.…”

Section: The Role Of Nephrologists In Kidney Biopsiesmentioning

confidence: 99%

The Native Kidney Biopsy

Hogan

Mocanu

Berns

2016

Clinical Journal of the American Society of Nephrology

228

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The kidney biopsy is the gold standard in the diagnosis and management of many diseases. Since its introduction in the 1950s, advancements have been made in biopsy technique to improve diagnostic yield while minimizing complications. Here, we review kidney biopsy indications, techniques, and complications in the modern era. We also discuss patient populations in whom special consideration must be given when considering a kidney biopsy and the important role that the kidney biopsy plays in nephrology training. These data are presented to develop best practice strategies for this essential procedure.

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Nephrology and the Percutaneous Renal Biopsy

Cited by 47 publications

References 34 publications

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes

Percutaneous Renal Biopsy of Native Kidneys: A Single-Center Experience of 1,055 Biopsies

The Native Kidney Biopsy

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