The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases

Canney, Mark; Gunning, Heather M.; Zheng, Yuyan; Rose, Caren; Jauhal, Arenn; Hur, Seo Am; Sahota, Anahat; Reich, Heather N.; Barbour, Sean J.

doi:10.1053/j.ajkd.2022.04.005

Cited by 22 publications

(28 citation statements)

References 33 publications

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“…Utilizing electronic health records of a population of 907 patients with glomerular disease, adults with nephrotic syndrome from primary glomerulopathy had over a 2.5-fold increased adjusted rate of incident acute coronary disease compared to matched controls (aHR, 2.58; 95% CI, 1.89 to 3.52) (6). Similar to these findings, a study by Canney et al in 2022 noted a 3 fold increase in rate of heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19) and a nearly two-fold increased adjusted rate of ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05) in a multivariable analysis (5).…”

Section: Non Immunosuppressive Managementsupporting

confidence: 58%

Treatment of membranous nephropathy: Perspectives on current and future therapies

Shah¹,

DeLaat²,

Cavanaugh³

2023

Front. Nephrol.

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Primary membranous nephropathy remains one of the most frequent causes of nephrotic syndrome in adults. It is an autoimmune disorder in which auto-antibodies target antigens at the podocytes cell membrane–basement membrane interface. Our understanding of membranous nephropathy has expanded dramatically as of late. After the initial discovery of the phospholipase A2 receptor auto-antibody in 2009, eight more antigens have been discovered. These discoveries have led to refinement in our understanding of the pathogenesis, diagnosis, and natural history of primary membranous nephropathy. Now, many experts advocate for redefining primary membranous nephropathy based on antigen, potentially shedding the primary and secondary nomenclature. Recently, therapies for primary membranous have also expanded. Immunosuppressive therapies like cyclophosphamide and rituximab, which primarily target B-cells, remain the cornerstone of therapy. However, there is still significant room for improvement, as many as 30-40% do not respond to this therapy according to recent trials. Additionally, drugs targeting complement, and other novel therapies are also under investigation. In this review we will discuss the available therapies for primary membranous nephropathy in light of recent clinic trials like GEMRITUX, MENTOR, RI-CYCLO, and STARMEN, as well as management strategies. While the last 10 years have seen a boom in our mechanistic understanding of this ever-diversifying disease, we are likely to see a similar boom in the therapeutic options in the years to come.

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Section: Non Immunosuppressive Managementsupporting

confidence: 58%

Treatment of membranous nephropathy: Perspectives on current and future therapies

Shah¹,

DeLaat²,

Cavanaugh³

2023

Front. Nephrol.

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“…6,11 These findings are consistent with recent reports that adults with primary glomerular disease and nephrotic syndrome are at relatively high risk of cardiovascular disease events. 12,13 While diabetes is well established as a major risk factor for CVD, studies have shown that the increased risk of CVD among individuals with diabetes is predominantly seen in those with associated nephropathy. [14][15][16] We found that mesangial expansion was associated with an increased risk of death or incident MACE even after adjustment for diabetes, hypertension, eGFR, and proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease

et al. 2023

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ImportanceHistologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events.ObjectiveTo assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE).Design, Setting, and ParticipantsThis prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021.ExposuresSemiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories.Main Outcomes and MeasuresThe main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria.ResultsOf 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models.Conclusions and RelevanceIn this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

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“…96 Recent registry data indicate that adults with primary glomerular disease have a 2.5 times higher risk of cardiovascular disease than the general population. 97 A specific uremic retention solute with an established role in immunosenescence is the protein-bound molecule indoxyl sulphate. This ligand of the acyl hydrocarbon receptor (AhR) downregulates the lymphocyte expression of CD28 at the transcriptional level.…”

Section: Immunosenescence and Uraemiamentioning

confidence: 99%

“…Of relevance, adolescents and young adults with ESKD because of glomerulonephritis had higher risk of cardiovascular disease in a large USRDS‐based observational study 96 . Recent registry data indicate that adults with primary glomerular disease have a 2.5 times higher risk of cardiovascular disease than the general population 97 …”

Section: Introductionmentioning

confidence: 99%

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Immunosenescence: an unexplored role in glomerulonephritis

2022

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Immunosenescence is a natural ageing phenomenon with alterations in innate and especially adaptive immunity and contributes to reduced antimicrobial defence and chronic low‐grade inflammation. This is mostly reflected by an increase in organ‐directed and/or circulating reactive and cytolytic terminally differentiated T cells that have lost their expression of the costimulatory receptor CD28. Apart from being induced by a genetic predisposition, ageing or viral infections (particularly cytomegalovirus infection), immunosenescence is accelerated in many inflammatory diseases and uraemia. This translates into an enhancement of vascular inflammation and cardiovascular disease varying from endothelial dysfunction to plaque rupture. Emerging data point to a mechanistic role of CD28null T cells in glomerulonephritis, where they initiate and propagate local inflammation in concordance with dendritic cells and macrophages. They are suitably equipped to escape immunological dampening by the absence of homing to lymph nodes, anti‐apoptotic properties and resistance to suppression by regulatory T cells. Early accumulation of senescent CD28null T cells precedes glomerular or vascular injury, and targeting these cells could open avenues for early treatment interventions that aim at abrogating a detrimental vicious cycle.

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The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases

Cited by 22 publications

References 33 publications

Treatment of membranous nephropathy: Perspectives on current and future therapies

Treatment of membranous nephropathy: Perspectives on current and future therapies

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease

Immunosenescence: an unexplored role in glomerulonephritis

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