IgA Nephropathy From Manifestation To Diagnosis And Treatment

IgA nephropathy (IgAN) is a common primary glomerular disease worldwide and an essential cause of end-stage renal disease (ESRD) in China. 20% to 40% of IgAN patients die within 10 to 20 years after the onset of Progression to ESRD. The speed and harm of IgAN progression can be seen. Therefore, timely diagnosis and intervention treatment are of great significance to IgAN patients.

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1. Pathogenesis of IgAN

IgA is an infection-fighting protein that, when deposited in kidney tissue, can cause red blood cells and proteins from kidney blood vessels to leak into the urine. After 10 to 20 years, due to continuous damage to the kidney tissue, complete renal failure may develop.

Clinically, lgAN 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, eventually causing a diffuse glomerular inflammatory response and forming IgAN.

2. Clinical manifestations of IgAN

Since IgAN has multiple pathological manifestations, the clinical features are quite different, but the main clinical images are hematuria and proteinuria.

(1) Hematuria. When gross hematuria occurs, the urine is red or dark brown, with smoky turbidity.
(2) Proteinuria. During lgAN, increased urinary protein loss, especially if it continues to increase, usually indicates a poor prognosis. If the loss of protein is large, such as more than 3 g/d, nephrotic syndrome can be triggered.
(3) Fatigue. Most patients experience fatigue, sometimes severe, and clinical symptoms such as sore throat, headache, dyspnea, loss of appetite, dry skin, pallor, and weakness. This discomfort and apparent fatigue can last for several hours.
(4) Flu-like symptoms. During lgAN, gross hematuria may be accompanied by flu-like symptoms. The patient feels general malaise (soreness and lethargy), fever, low back pain, and muscle pain. Although some patients have all the above symptoms, they are not accompanied by hematuria.
(5) Allergic reactions. In the pathogenesis of lgAN, allergic reactions are often mixed. Many patients are prone to itching and large areas of urticaria, which are related to IgA deposition.

3. Differential diagnosis of IgAN

(1) 4-step process. When the patient has symptoms such as hematuria, proteinuria, and edema, and IgAN is suspected

First, do a urine test
Followed by routine blood tests and renal function tests
Again, kidney B-ultrasound examination

If the results of these three tests cannot diagnose IgAN, a renal biopsy is required at this time. The diagnosis of IgAN must be based on renal biopsy. Only when granular IgA deposits are seen in the glomerular mesangium can it be confirmed as IgAN.

(2) 1 identification. In the diagnosis process of IgAN, it needs to be differentiated from acute post-streptococcal glomerulonephritis, allergic purpura, and allergic purpura nephritis.

4. IgAN treatment plan

(1) Optimize supportive care. IgAN should initiate optimal supportive care, including lifestyle changes, blood pressure management, and cardiovascular risk intervention. For patients with 24-hour urine protein quantity > 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 therapy drugs sodium-glucose cotransporter 2 inhibitors, and endothelin receptor antagonists have achieved certain results in the treatment of IgAN.

(2) Glucocorticoid treatment. The 2021 KDIGO guidelines recommend that, for patients who have received at least 3 months of optimal supportive treatment but still have proteinuria >1 g/d, 6 months of glucocorticoid therapy should be given. Studies have confirmed that oral glucocorticoid therapy can reduce proteinuria in IgAN patients and reduce the risk of developing ESRD. The results of the 2022 TESTING study gave a reduced-dose hormone regimen: 0.4 mg/(kg·d), the maximum dose is 32 mg/d, and the dose is gradually reduced by 4 mg every month for a course of 6 to 9 months. In addition, the regimen of low-dose corticosteroids combined with sulfonamides to prevent infection can reduce the incidence of serious adverse reactions by more than 70%.

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

In addition, there are locally targeted drugs that modulate IgAN mucosal immunity, such as:

New budesonide dosage form
Potential TLR-9 inhibitors such as hydroxychloroquine
B cell activating factor blockers such as Tetacept
Complement pathway inhibitors such as Iptacopan and Narsoplimabdeng
These drugs can treat IgAN to some extent.

for more information:ali.ma@wecistanche.com