Publications by authors named "Andrea Havasi"

Article Synopsis
  • - Immunoglobin light chain (AL) amyloidosis is a rare disease mainly affecting the heart and kidneys through amyloid fibril buildup, making organ-specific evaluations crucial for understanding the disease's impact and guiding treatment.
  • - To promote new treatment developments, the Amyloidosis Forum convened to create guidelines for clinical trials, focusing on identifying effective assessment measures particularly from the insights of the Renal Working Group.
  • - Key recommendations include using estimated glomerular filtration rate (eGFR) and proteinuria to determine trial eligibility and track patient responses, while highlighting the importance of timely and accurate evaluation of treatment effects.
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Animal models of selective breeding for extremes in emotionality are a strong experimental approach to model psychopathologies. They became indispensable in order to increase our understanding of neurobiological, genetic, epigenetic, hormonal, and environmental mechanisms contributing to anxiety disorders and their association with depressive symptoms or social deficits. In the present review, we extensively discuss Wistar rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviour on the elevated plus-maze.

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Various types of systemic amyloidosis can wreak havoc on the architecture and functioning of the kidneys. Amyloidosis should be suspected in patients with worsening kidney function, proteinuria, and multisystem involvement, but isolated kidney involvement also is possible. Confirming the amyloidosis type and specific organ dysfunction is of paramount importance to select the appropriately tailored treatment and aim for better survival while avoiding treatment-associated toxicities.

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Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020.

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Article Synopsis
  • High-dose melphalan and stem cell transplantation (HDM/SCT) shows long-term effectiveness in treating AL amyloidosis, with 39% of patients achieving complete hematologic response (CR).
  • The median CR duration is 12.3 years, while overall survival (OS) for patients with CR is impressive, reaching up to 15 years for some.
  • Factors such as elevated dFLC levels and plasma cell percentages are linked to shorter event-free survival (EFS), allowing the development of a risk score to better predict outcomes.
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Rationale & Objective: Test the feasibility of replacing 24-hour urine collection with a single voided urinary protein-creatinine ratio (UPCR) in patients with amyloid light-chain (AL) amyloidosis.

Study Design: Retrospective study examining the correlation between a 24-hour urine measurement and UPCR at various proteinuria levels using a linear regression analysis with Pearson's correlation coefficient (r). We assessed how using these 2 different measurements would alter the diagnosis, staging, and kidney response assessment in patients with AL amyloidosis.

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Nucleophosmin (NPM), a nucleolar-based protein chaperone, promotes Bax-mediated mitochondrial injury and regulates cell death during acute kidney injury. However, the steps that transform NPM from an essential to a toxic protein during stress are unknown. To localize NPM-mediated events causing regulated cell death during ischemia, wild type (WT) and Hsp70 mutant proteins with characterized intracellular trafficking defects that restrict movement to either the nucleolar region (M45) or cytosol (985A) were expressed in primary murine proximal tubule epithelial cells (PTEC) harvested from Hsp70 null mice.

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Background: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear.

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Background: Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known.

Methods: This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT.

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Dysproteinemic kidney diseases are disorders that occur as the result of lymphoproliferative (B cell or plasma cell) disorders that cause kidney damage via production of nephrotoxic monoclonal immunoglobulins or their components. These monoclonal immunoglobulins have individual physiochemical characteristics that confer specific nephrotoxic properties. There has been increased recognition and revised characterization of these disorders in the last decade, and in some cases, there have been substantial advances in disease understanding and treatments, which has translated to improved patient outcomes.

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The function of site-specific phosphorylation of nucleophosmin (NPM), an essential Bax chaperone, in stress-induced cell death is unknown. We hypothesized that NPM threonine 95 (T95) phosphorylation both signals and promotes cell death. In resting cells, NPM exclusively resides in the nucleus and T95 is nonphosphorylated.

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Introduction: Monoclonal Ig deposition disease (MIDD) frequently leads to kidney failure, and a large proportion of these patients would greatly benefit from kidney transplantation. However, data on kidney transplantation outcomes in MIDD are limited.

Methods: This was a retrospective analysis of long-term renal outcomes of 23 patients with MIDD, including 6 patients who underwent kidney transplantation.

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Gentamicin is a nephrotoxic antibiotic that causes acute kidney injury (AKI) primarily by targeting the proximal tubule epithelial cell. The development of an effective therapy for gentamicin-induced renal cell injury is limited by incomplete mechanistic insight. To address this challenge, we propose that RNAi signal pathway screening could identify a unifying mechanism of gentamicin-induced cell injury and suggest a therapeutic strategy to ameliorate it.

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The present review discusses current developments and outcomes of renal transplantation in systemic amyloidosis. Amyloidosis can wreak havoc on the architecture and functioning of the kidneys, leading to end-stage renal disease. In recent years, the available treatments, especially for light-chain amyloidosis but also for several of the underlying inflammatory diseases that cause amyloid A amyloidosis have expanded leading to prolonged survival albeit frequently with renal failure.

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The diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (CR) or very good partial hematologic response (VGPR) but with renal organ relapse is not clear. We present eight patients with AL amyloidosis who had a repeat kidney biopsy performed. AL amyloidosis was initially diagnosed by a kidney biopsy.

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Therapies for AL amyloidosis have dramatically improved, leading to longer patient survival; however, more AL amyloidosis patients are reaching end-stage renal disease (ESRD). There are no clear guidelines regarding eligibility for kidney transplantation in patients with AL amyloidosis, and data on outcomes are limited. We evaluated the clinical and laboratory data of 49 patients who were followed in the Amyloidosis Center at Boston University and underwent kidney transplantation at a center in the United States between 1987-2017.

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Ischemic AKI lacks a urinary marker for early diagnosis and an effective therapy. Differential nucleophosmin (NPM) phosphorylation is a potential early marker of ischemic renal cell injury and a therapeutic target. Differential NPM phosphorylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithelial cells, fresh kidney tissue, and urine before and after ischemic injury.

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The kidney is the most common organ affected by immunoglobulin light-chain (AL) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD), often leading to end-stage renal disease (ESRD). High-dose melphalan and stem cell transplantation (HDM/SCT) is effective for selected patients with AL amyloidosis, with high rates of complete hematologic response and potential for improved organ dysfunction. Data on tolerability and response to HDM/SCT in patients with ESRD due to AL amyloidosis and MIDD are limited.

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Background: The extent of interstitial fibrosis on kidney biopsy is regarded as a prognostic indicator and guide to treatment. Patients with extensive fibrosis are assigned to supportive treatments with the expectation that they have advanced beyond the point at which immunosuppressive or other disease-modifying therapies would be of benefit. Our study highlights some of the limitations of using interstitial fibrosis to predict who will develop end-stage renal disease (ESRD).

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Protein mimotopes, or blocking peptides, are small therapeutic peptides that prevent protein-protein interactions by selectively mimicking a native binding domain. Inexpensive technology facilitates straightforward design and production of blocking peptides in sufficient quantities to allow preventive and therapeutic trials in both in vitro and in vivo experimental disease models. The kidney is an ideal peptide target, since small molecules undergo rapid filtration and efficient bulk absorption by tubular epithelial cells.

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Proteinuria is a major risk factor for chronic kidney disease progression. Furthermore, exposure of proximal tubular epithelial cells to excess albumin promotes tubular atrophy and fibrosis, key predictors of progressive organ dysfunction. However, the link between proteinuria and tubular damage is unclear.

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