Is it time for personalized therapy in IgA nephropathy patients?

Schena, Francesco Paolo; Cox, Sharon Natasha

doi:10.1007/s40620-023-01745-2

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…[4][5][6] Despite the increasing number of new potential options, immunosuppressive therapies such as systemic corticosteroids, cyclophosphamide, and mycophenolate remain to be commonly used, particularly for patients at high risk of kidney function decline. 7 Because of their ambiguous effectiveness and undesirable side effects, these approaches have been controversial. 8 Thus, more targeted and effective treatments are still needed.…”

Section: Introductionmentioning

confidence: 99%

Circulating Proteins and IgA Nephropathy

Tang,

Chen,

et al. 2024

JASN

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Background: The therapeutic options for IgA nephropathy are rapidly evolving, but early diagnosis and targeted treatment remain challenging. We aimed to identify circulating plasma proteins associated with IgA nephropathy by proteome-wide mendelian randomization studies across multiple ancestry populations. Methods: In this study, we applied Mendelian randomization and colocalization analyses to estimate the putative causal effects of 2615 proteins on IgA nephropathy in Europeans and 235 proteins in East Asians. Following two-stage network Mendelian randomization, multi-trait colocalization analysis and protein-altering variant annotation were performed to strengthen the reliability of the results. A protein-protein interaction network was constructed to investigate the interactions between the identified proteins and the targets of existing medications. Results: Putative causal effects of 184 and 13 protein-disease pairs in European and East Asian ancestries were identified, respectively. Two protein-disease pairs showed shared causal effects across them (CFHR1 and FCRL2). Supported by the evidence from colocalization analysis, potential therapeutic targets were prioritized and four drug-repurposing opportunities were suggested. The protein-protein interaction network further provided strong evidence for existing medications and pathways that are known to be therapeutically important. Conclusions: Our study identified a number of circulating proteins associated with IgA nephropathy and prioritized several potential drug targets that require further investigation.

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Section: Introductionmentioning

confidence: 99%

Circulating Proteins and IgA Nephropathy

Tang,

Chen,

et al. 2024

JASN

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IgA Nephropathy: What Is New in Treatment Options?

Scarpioni,

Valsania

2024

Kidney and Dialysis

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IgA nephropathy (IgAN), first described in 1968, is one of the most common forms of glomerulonephritis and can progress to end-stage kidney disease (ESKD) in 25 to 30 percent of patients within 20 to 25 years from the onset. It is histologically characterized by mesangial proliferation with prominent IgA deposition. The prognosis may be difficult to predict, but important risk factors for disease progression of kidney disease have been recognized: usually proteinuria above 0.75–1 g/day with or without hematuria, hypertension, high-risk histologic features (such as crescent formation, immune deposits in the capillary loops, mesangial deposits, glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular disease), and a reduced Glomerular Filtration Rate (GFR). In the absence of reliable specific biomarkers, current standards of care are addressed to decrease proteinuria, as a surrogate endpoint, and control blood pressure. For a long time, corticosteroids have been considered the only cure for proteinuric patients or those at risk of progression to ESKF; however, unfortunately, like other immunosuppressive agents, they are burdened with high collateral risks. Therefore, optimal treatment remains a challenge, even if, to date, clinicians have many more options available. Here, we will review the main therapies proposed, such as the stronghold of RAAS inhibition and the use of SGLT2 inhibitors; it is expected that ongoing clinical trials may find other therapies, apart from corticosteroids, that may help improve treatment, including both immunosuppressive monoclonal antibodies and other strategies. At the current time, there are no disease-specific therapies available for IgAN, because no largescale RCTs have demonstrated a reduction in mortality or in major adverse kidney or cardiovascular events with any therapy.

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Is it time for personalized therapy in IgA nephropathy patients?

Cited by 2 publications

References 9 publications

Circulating Proteins and IgA Nephropathy

Circulating Proteins and IgA Nephropathy

IgA Nephropathy: What Is New in Treatment Options?

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