From the Guidelines
Berger disease, also known as IgA nephropathy, should be managed with a multifaceted approach, focusing on optimized supportive care, including RAS blockade, blood pressure control, and lifestyle modifications, as the primary treatment strategy. This approach is based on the latest guideline recommendations from the KDIGO 2021 guideline for the management of glomerular diseases 1. The management of IgA nephropathy should prioritize the reduction of proteinuria to under 1 g/d, which is a surrogate marker of improved kidney outcome.
Key Components of Management
- RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d, as recommended by the KDIGO guideline 1
- Blood pressure control is essential, with a target blood pressure of less than 130/80 mmHg
- Lifestyle modifications, including dietary counseling, smoking cessation, weight control, and exercise, are crucial in managing the disease
- The International IgAN Prediction Tool can be used to assess disease prognosis, but it should not be used to determine the likely impact of any particular treatment regimen 1
Treatment of High-Risk Patients
- If proteinuria stays above 0.75–1 g/d despite at least 90 days of optimized supportive care, a 6-month course of glucocorticoid therapy may be considered, but with caution in patients with certain comorbidities, such as diabetes, obesity, or latent infections 1
- Other immunosuppressive therapies, including azathioprine, cyclophosphamide, and rituximab, are not recommended in IgAN, except in specific situations, such as rapidly progressive IgAN 1
- New therapies, including SGLT2 inhibitors and complement inhibitors, are being evaluated for the treatment of high-risk IgAN patients, but their use is not yet recommended in clinical practice 1
From the Research
Definition and Overview of Berger Disease
- Berger disease, also known as IgA nephropathy, is a kidney disease characterized by the deposition of IgA antibodies in the glomeruli, leading to inflammation and damage to the kidneys 2, 3, 4, 5, 6.
- It is the most common primary glomerulonephritis worldwide and can lead to end-stage renal disease in 20-30% of patients 4, 6.
Symptoms and Diagnosis
- Clinical manifestations of IgA nephropathy vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis 6.
- IgA nephropathy can only be diagnosed by kidney biopsy 6.
Treatment and Management
- Extensive, optimized supportive care is the mainstay of therapy for patients with IgA nephropathy, including management of blood pressure and lipids, improvement or stabilization of kidney function, and reduction of proteinuria 2, 3, 4, 6.
- Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are recommended as first-line therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90 mm Hg 2, 3, 4.
- Corticosteroids could be considered as add-on or monotherapy for patients with urine protein >1 g/day with preserved renal function 2, 3, 4, 6.
- Novel targeted therapies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components, are being tested in clinical trials 6.
Pathophysiology
- IgA nephropathy has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring 6.