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Current Treatment Options for IgA Nephropathy

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IgA Nephropathy, also known as Berger's disease, is a kidney disorder that results from deposits of the immunoglobulin A (IgA) in the glomeruli within the kidneys. This condition can lead to local inflammation, eventually impairing the kidneys' ability to filter wastes from the blood effectively. As a relatively common form of glomerulonephritis, IgA Nephropathy can vary significantly in its progression among individuals—some may remain symptom-free, others may experience a slow progression to kidney failure, and a few may rapidly progress to end-stage renal disease. Given the complexity of the pathogenesis of IgA nephropathy and the involvement of multiple factors and mechanisms, treatment options are varied. This article explores the current treatment options for IgA Nephropathy, focusing on slowing the disease's progression, managing symptoms, and preserving kidney function as much as possible.

Intestinal Mucosal B Cell Immunomodulators

Budesonide enteric capsules (Nefecon) are precisely released at the Peyer's patch lymph node at the end of the small intestine through a dual delayed and sustained-release innovative formulation process, which regulates the activity of intestinal mucosal B cells and acts on the upstream stage of the pathogenesis of IgA nephropathy, thus truly achieving etiological treatment. The drug was first approved by the U.S. Food and Drug Administration (FDA) in November 2021 for use in patients with IgA nephropathy at risk of progression to reduce proteinuria. It was fully approved by the FDA in December 2023 for use in patients with IgA nephropathy at risk of progression to slow loss of kidney function, without restrictions on baseline levels of proteinuria. Clinical studies have confirmed that budesonide enteric-coated capsules can significantly improve renal function in patients with IgA nephropathy, delay the decline in estimated glomerular filtration rate (eGFR), reduce proteinuria, reduce hematuria, and are safe. These features help minimize systemic adverse effects.

Fig. 1: Evaluation of targeted-release formulation of budesonide for the treatment of primary IgAN. (Barratt, Jonathan, et al., 2023)Fig 1. Evaluation of targeted-release formulation of budesonide for the treatment of primary IgAN.1

Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors

One of the cornerstone treatments for IgA Nephropathy involves the control of blood pressure. High blood pressure is not only a common symptom of this condition but also a critical factor that can accelerate kidney damage. The RAAS plays an important role in maintaining blood pressure and volume balance. RAAS inhibitors can slow down kidney disease progression by reducing glomerular static pressure. For a long time, RAAS inhibitors have been recommended by guidelines and commonly used in clinical practice as standard supportive treatment for IgA nephropathy.

Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors

SGLT2 inhibitors are a new type of antidiabetic drug that has been proven to provide renal protection in recent years, regardless of whether the patient has diabetes. A subgroup analysis of the DAPA-CKD study confirmed that in patients with IgA nephropathy, Dapagliflozin significantly delays the decline in renal function and the progression to ESRD, and reduces proteinuria. The EMPA-KIDNEY study further corroborated the potential benefits of SGLT2 inhibitors for IgA nephropathy.

Glucocorticoids

Systemic hormones have long been used in clinical practice; they exert renal protective effects through anti-inflammatory and immune suppression, but their therapeutic effects on IgA nephropathy remain controversial. The three-year follow-up results of the European multicenter STOP study showed that the combination of systemic hormone immune suppression treatment on the basis of supportive treatment did not reduce the risk of the primary endpoint of complete clinical remission (proteinuria <0.2 g/d and stable kidney function), and systemic hormone treatment significantly increased the risk of adverse events such as infection and weight gain. The TESTING and TESTING 2.0 study conducted in China and international multicenter sites supports that for patients with IgA nephropathy at risk of progression, oral methylprednisolone significantly delays kidney function decline, kidney failure, or kidney disease death risk compared to placebo, but also increases the risk of serious adverse events.

Tonsillectomies

Patients with IgA nephropathy often present with gross hematuria after acute tonsillitis, so some scholars advocate tonsillectomy as one of the treatment methods for IgA nephropathy. However, there is much controversy about this therapy, and currently, the favorable evidence mainly comes from Japanese studies, where tonsillectomy has been approved for use in combination with hormone shock therapy for the treatment of IgA nephropathy. Therefore, the 2021 KDIGO guidelines only recommend that Japanese IgA nephropathy patients may consider using this approach.

Conclusion

The management of IgA Nephropathy requires a multifaceted approach that includes controlling blood pressure, reducing proteinuria, managing symptoms, and slowing the progression of kidney damage. The choice of treatment is highly individualized, based on the severity of the disease, the patient's overall health, and the presence of any complicating factors. With ongoing research and the development of new therapeutic strategies, there is hope for more effective treatments in the future. Patients with IgA Nephropathy should work closely with their healthcare team to monitor their condition and adjust their treatment plan as necessary to maintain kidney function and quality of life.

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Reference

  1. Barratt, Jonathan, et al. "Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy." Kidney international 103.2 (2023): 391-402.

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