-
Indian Journal of Nephrology 2024Monoclonal gammopathy of renal significance (MGRS) has gained importance because identifying the monoclonal deposit and addressing it, rather than treating renal...
Monoclonal gammopathy of renal significance (MGRS) has gained importance because identifying the monoclonal deposit and addressing it, rather than treating renal dysfunction as the primary pathology, has salvaged the patients from progressing into end-stage renal disease. Since it affects elderly population, there could be a propensity to misdiagnose them with cardiorenal syndrome. We present four patients of MGRS diagnosed from our center. They presented with proteinuria or unexplained renal dysfunction. Three of the patients were diagnosed to have amyloidosis, of which two had lambda-type and one had kappa amyloidosis. The fourth patient had fibrillary glomerulonephritis with kappa restriction, further evaluation of which led to diagnosis of chronic lymphocytic leukemia. Absence of "M" band in protein electrophoresis and a normal bone marrow study should not stop physicians from further evaluation. Quantitative serum immunofixation electrophoresis and electron microscopic examination of renal biopsy have become a comprehensive diagnostic tool in such patients.
PubMed: 38645913
DOI: 10.4103/ijn.ijn_329_22 -
Current Heart Failure Reports Jun 2024Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection... (Review)
Review
PURPOSE OF REVIEW
Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO).
RECENT FINDINGS
We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction.
Topics: Humans; Heart Failure; Exercise Test; Stroke Volume; Amyloidosis; Retrospective Studies; Oxygen Consumption; Male; Female; Aged; Echocardiography; Exercise Tolerance; Middle Aged; Cardiomyopathies
PubMed: 38635117
DOI: 10.1007/s11897-024-00661-1 -
Therapeutic Innovation & Regulatory... Jul 2024Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To... (Review)
Review
Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Clinical Trials as Topic; Drug Development; Endpoint Determination; United States
PubMed: 38632158
DOI: 10.1007/s43441-024-00641-6 -
Cureus Mar 2024Macular amyloidosis is primary localized cutaneous amyloidosis (PLCA). It is described by the extracellular accumulation of heterogenic amyloid proteins in the skin that...
Macular amyloidosis is primary localized cutaneous amyloidosis (PLCA). It is described by the extracellular accumulation of heterogenic amyloid proteins in the skin that does not affect the systemic immune system, causing hyperpigmented patches. It is a prevalent skin disorder of young female adults, especially in India, since it affects the population with darker skin. History of frictional rub on the skin is typically present, such as using loofah or bathing scrubs or stones. The case presented below is of a 23-year-old female who presented with a hyperpigmented patch on the upper back of both sides and extensor surface of arms and did not have any history of usage of loofah on those areas, compelling us to research more on the other causative factors (genetic predisposition, infectious agents, and UV radiation are probable causative factors) for macular amyloidosis. This condition is not entirely cured; it is managed symptomatically only to improve cosmetic outcomes.
PubMed: 38623100
DOI: 10.7759/cureus.56248 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Leukemia Jun 2024
Topics: Humans; Bortezomib; Dexamethasone; Cyclophosphamide; Immunoglobulin Light-chain Amyloidosis; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Male; Female; Aged; Treatment Failure; Middle Aged
PubMed: 38594348
DOI: 10.1038/s41375-024-02243-5 -
Journal of Clinical Medicine Feb 2024Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The... (Review)
Review
Cardiac amyloidosis is caused by amyloid fibrils that deposit in the myocardial interstitium, causing restrictive cardiomyopathy and eventually death. The electromechanical, inflammatory, and autonomic changes due to amyloid deposition result in arrhythmias. Atrial fibrillation is by far the most common arrhythmia. The rate control strategy is generally poorly tolerated due to restrictive filling physiology and heart rate dependance, favoring adoption of the rhythm control strategy. Anticoagulation for stroke prophylaxis is warranted, irrespective of CHADS-VASc score in patients with a favorable bleeding profile; data on left appendage closure devices are still insufficient. Ventricular arrhythmias are also not uncommon, and the role of implantable cardioverter-defibrillator in cardiac amyloidosis is controversial. There is no evidence of improvement in outcomes when used for primary prevention in these patients. Bradyarrhythmia is most commonly associated with sudden cardiac death in cardiac amyloidosis. Pacemaker implantation can help provide symptomatic relief but does not confer mortality benefit.
PubMed: 38592132
DOI: 10.3390/jcm13051300 -
Scientific Reports Apr 2024Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly,...
Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.
Topics: Humans; Retrospective Studies; Kidney Diseases; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Prognosis; Hematologic Neoplasms
PubMed: 38561447
DOI: 10.1038/s41598-024-58467-z -
Cureus Feb 2024Systemic amyloidosis is caused by the extracellular deposition of misfolded proteins in various organs and usually leads to organ dysfunction. The two common subtypes...
Systemic amyloidosis is caused by the extracellular deposition of misfolded proteins in various organs and usually leads to organ dysfunction. The two common subtypes include light-chain amyloidosis and transthyretin amyloidosis. Deposition of these proteins in the heart can lead to infiltrative and restrictive cardiomyopathy, commonly manifesting as heart failure with preserved ejection fraction. However, systolic heart failure with reduced ejection fraction is mainly seen in the advanced stages of the disease. Here, we present the case of a 53-year-old female who presented with new-onset heart failure with reduced ejection fraction with no prior symptoms or diagnosis of amyloidosis and diastolic dysfunction.
PubMed: 38558722
DOI: 10.7759/cureus.55271