Learn in one article | How much do you know about IgA nephropathy from clinical manifestations to treatment?

IgA nephropathy (IgAN) is a common primary glomerular disease worldwide and an important cause of end-stage renal disease (ESRD) in my country. 20% to 40% of IgAN patients progress to ESRD within 10 to 20 years after onset[1]. This shows the speed and harm of IgAN progression. Therefore, timely diagnosis and intervention treatment are of great significance to IgAN patients.

Pathogenesis of IgAN

IgA is a protein that can fight infection. When deposited in kidney tissue, it can cause red blood cells and proteins in the renal blood vessels to leak into the urine. After 10 to 20 years, due to the continuous damage to the kidney tissue, it can develop into complete renal failure. Clinically, IgAN is generally regarded as an immune complex-mediated or immunogenic disease. This means that although immune dysfunction does not directly cause the disease, it plays a special role in its occurrence and development, ultimately causing diffuse glomerular inflammatory reactions and the formation of IgAN.

The clinical manifestations of IgAN are mainly hematuria and proteinuria

Since IgAN has a variety of pathological manifestations, the clinical characteristics vary greatly, but the main clinical manifestations are hematuria and proteinuria.

(1) Hematuria. When there is macroscopic hematuria, the urine is red or dark brown and has a smoky turbidity.

(2) Proteinuria. During the course of IgAN, increased urinary protein loss, especially sustained increase, usually indicates a poor prognosis. If the amount of protein loss is large, such as more than 3 g/d, it may induce nephrotic syndrome.

(3) Fatigue. Most patients will experience fatigue, which is sometimes severe. They may also experience clinical symptoms such as sore throat, headache, dyspnea, lack of appetite, dry skin, paleness, and physical weakness. This discomfort and obvious fatigue can last for several days or longer.

(4) Flu-like symptoms. During the course of lgAN, gross hematuria may be accompanied by flu-like symptoms. Patients feel general discomfort (soreness and drowsiness), slight fever, back pain and muscle pain. Some patients have all of the above symptoms but do not have hematuria.

(5) Allergic reactions. In the course of IgA disease, allergic reactions are often involved. Many patients are prone to itching and large-area urticaria, which may be related to IgA deposition.

Definitive diagnosis of IgAN: 4 steps, 1 differential

(1) 4-step process. When a patient has symptoms such as hematuria, proteinuria, and edema and is suspected of having IgAN, a routine urine test should be performed first, followed by a routine blood test and renal function test, and finally a renal B-ultrasound examination. If the results of these three tests cannot clearly diagnose IgAN, a renal biopsy is required. The diagnosis of IgAN must be based on a renal biopsy. Only when granular IgA deposits are seen in the glomerular mesangial area can it be confirmed as IgAN.

(2) Differentiation. In the diagnosis of IgAN, it is necessary to differentiate it from acute post-streptococcal glomerulonephritis, Henoch-Schönlein purpura, and Henoch-Schönlein purpura nephritis.

How is IgAN treated?

(1) Optimize supportive care. Optimize supportive care should be initiated first for IgAN, including lifestyle changes, blood pressure management, and intervention for cardiovascular risks. For patients with 24-hour urine protein quantification > 0.5 g, regardless of whether they have hypertension, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are recommended for treatment. At the same time, new optimized supportive care drugs such as sodium-glucose co-transporter 2 inhibitors and endothelin receptor antagonists have certain effects in the treatment of IgAN.

(2) Glucocorticoid treatment. The 2021 KDIGO guidelines recommend that patients who have received at least 3 months of optimized supportive care but whose proteinuria is still greater than 1 g/d should be given 6 months of glucocorticoid treatment.

Studies have confirmed that oral glucocorticoid therapy can reduce proteinuria in IgAN patients and reduce their risk of progression to ESRD. The results of the 2022 TESTING study gave a reduced-dose hormone regimen: 0.4 mg/(kg·d), with a maximum dose of 32 mg/d, gradually reducing the dose by 4 mg per month, and a course of treatment of 6 to 9 months. In addition, a low-dose hormone combined with sulfonamide to prevent infection can reduce the incidence of serious adverse reactions by more than 70%.

(3) Immunosuppressant therapy. For some patients with severe conditions, intravenous high-dose methylprednisolone "shock therapy" may be required. However, for patients with mild symptoms, oral corticosteroids such as prednisone are usually recommended to stabilize the glomerular basement membrane and prevent the passage of large molecular proteins. Generally, prednisone is taken once every morning or every other morning to minimize its adverse reactions. In addition, tumor chemotherapy cytotoxic agents such as cyclophosphamide and some drugs used to prevent rejection reactions in organ transplantation, such as azathioprine and cyclosporine, have strong immunosuppressive effects and can be used to treat IgAN.

In addition, there are drugs that regulate the local targeted release of IgAN mucosal immunity, such as new budesonide formulations, potential TLR-9 inhibitors such as hydroxychloroquine, B cell activating factor blockers such as tadalafil, complement pathway inhibitors such as Iptacopan and Narsoplimabdeng, etc. These drugs can treat IgAN to a certain extent.

References

[1]MORI YAM A T.Clinical and histological features and therapeutic strategies for IgA nephropathy[J].Clin Exp Nephrol,2019,23(9):1089-1099.

[2] Liu Jingduo. Clinical manifestations, pathogenesis, diagnosis and treatment progress of IgA nephropathy[J]. Medical Journal of Armed Police Forces, 2014, 25(09): 865-868.