IgA nephropathy

Disease Description (Causes and Symptoms)

• Summary of definition: A chronic glomerulonephritis caused by predominant deposition of immunoglobulin A (IgA)-containing immune complexes in the mesangium (central part) of the glomeruli (the most common form).
• Causes and pathophysiology: Abnormally glycosylated IgA1 binds to autoantibodies to form immune complexes → deposits in the mesangium → activation of complement (mainly the alternative and lectin pathways), mesangial proliferation, and inflammation → glomerular damage. A family history is involved in some cases (approximately 10–15%).
• Main symptoms:
  • Recurrent or intermittent visible hematuria (often occurring immediately after an upper respiratory tract infection)
  • Microscopic hematuria (which may be persistent)
  • Proteinuria (varying from mild to nephrotic-range)
  • High blood pressure, flank pain, and edema (when proteinuria is severe)
  • In some cases, progression to rapidly progressive glomerulonephritis (rapidly progressive GN)
• Clinical course: The range of symptoms is broad — some people have only asymptomatic hematuria, while others may develop progressive proteinuria and declining kidney function, progressing to end-stage renal disease (ESRD) within several years to several decades (some reports indicate that approximately 15–25% progress to ESRD after 10 years and approximately 20–30% after 20 years among those with proteinuria or kidney failure).

Treatment Methods

• Diagnostic-based principles: A kidney biopsy (predominant mesangial IgA deposition on immunofluorescence) is the definitive diagnostic method. Treatment follows a stepwise approach based on risk factors (amount of proteinuria, eGFR, blood pressure, and histologic findings).
• 1. Supportive treatment (recommended first for all patients)
  • Blood pressure control: The general target is ≤130/80 mmHg (varies depending on the patient’s condition).
  • RAAS blockers (ACE inhibitors or ARBs): First-line choices to reduce proteinuria and protect kidney function.
  • Salt restriction (low-salt diet), weight management, smoking cessation, and blood glucose management (if diabetes is present).
  • Avoid nephrotoxic medications such as NSAIDs.
  • Follow-up with regular testing for proteinuria, hematuria, and kidney function.
• 2. Drug treatment (for patients with persistent proteinuria or a risk of progression)
  • Corticosteroids: May be considered in selected patients whose proteinuria persists despite optimal conservative treatment (3–6 months), generally >1 g/day or high risk based on ACR criteria. The decision should be based on an assessment of the benefits and the risks of adverse effects such as infection and osteoporosis.
  • Immunosuppressants (azathioprine, cyclophosphamide, etc.): Used for rapidly progressive forms (when there are many crescents) or high-risk patients inadequately controlled with steroids alone. Adverse effects, including an increased risk of infection, must be monitored during treatment.
  • SGLT2 inhibitors (e.g., dapagliflozin): Recent studies of the overall CKD population included the IgA nephropathy subtype and showed kidney-protective effects, so these may be considered as adjunctive treatment (based on a nephrologist’s judgment).
  • Other treatments (used locally or regionally): Tonsillectomy (attempted in some regions, such as Japan, when recurrent upper respiratory tract infections are present), omega-3 fatty acids (limited effectiveness) — these are not recommended as standard systemic therapies.
• 3. Acute and severe cases
  • Rapidly progressive glomerulonephritis (extensive crescent formation): Combination treatment with high-dose steroids and cyclophosphamide, with plasmapheresis if necessary.
• Follow-up and monitoring
  • Blood pressure and urinalysis (microscopy and dipstick) monthly or as recommended by the treating physician.
  • Proteinuria (ACR or 24-hour urine protein), creatinine, and eGFR every 3–6 months or more frequently depending on the condition.
• Precautions (related to treatment)
  • During immunosuppressive treatment, be aware of infection, osteoporosis, gastrointestinal complications, and worsening blood glucose levels.
  • When planning pregnancy, medications such as ACE inhibitors/ARBs must be changed because they are toxic to the fetus.

Checklist Before an Outpatient Visit (Including Example Questions)

• Recommended items to prepare or bring
  • A list of all medications currently being taken (including prescription drugs, OTC drugs, herbal medicines, and supplements), with dosages
  • Recent test results (creatinine, eGFR, urinalysis, urine albumin/creatinine ratio (ACR), or 24-hour urine protein)
  • Previous kidney biopsy results (slides/reports, if available)
  • Blood pressure records (home blood pressure records are useful if available)
  • A record of symptom changes (timing and color of hematuria and whether it was associated with an infection, etc.), presence of edema, and weight changes
  • Family history (kidney disease and history of hematuria) and recent infection history (especially upper respiratory tract infections)
• Questions to write down in advance for the outpatient visit (examples)
  • What was the proteinuria level on my recent urine test (ACR or g/24 h)?
  • What is my blood pressure target, and what is the current treatment plan?
  • Do any of my current medications need to be stopped or adjusted?

Examples of General Questions to Ask the Doctor

• What are the expected benefits and possible side effects of this medication (e.g., steroids, ACE inhibitors/ARBs, or SGLT2 inhibitors)?
• What is my prognosis (based on my proteinuria and kidney function values)?
• What specifically should I adjust in my lifestyle (diet, exercise, and salt intake)?
• What additional tests are needed to prevent infections if immunosuppressive treatment (or steroids) is started?

Examples of Disease-Specific Questions

• What are the findings of the Oxford classification (M, E, S, T, C) in my recent kidney biopsy (or previous biopsy), and what do they mean for my prognosis?
• I (or a family member) repeatedly develop visible hematuria after a cold. Would infection prevention (e.g., tonsil-related measures) or tonsillectomy be helpful in my case?

(Note: Treatment recommendations and values vary depending on the individual patient’s circumstances, including age, eGFR, and comorbidities. Please consult a nephrology specialist for specific diagnosis and treatment.)