IgA nephropathy medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[2], Ali Poyan Mehr, M.D. [3]

According to “The National Kidney Foundation: Kidney Disease – Improving Global Outcomes” (NKF-KDIGO)^[1] in 2012, the management and treatment recommendations of primary IgA nephropathy are as follows:

• Prevent the occurrence of repeated episodes of AKI and persistent macroscopic hematuria^[2]
• Reduce proteinuria to less than 1 g/24 hrs in adults and to less than 0.5 g/24 hrs in children regardless of baseline proteinuria at diagnosis^[2][3]
• Control blood pressure to < 130/80 mmHg if proteinuria is > 0.3 g/24 hrs and more aggressively to <125/75 mmHg if proteinuria is 1g/24 hrs^[2]
• Reduce avoidable risk factors, such as obesity. Weight loss to a BMI<25 kg/m2 is recommended to patients with IgA nephropathy to reduce obesity and cardiovascular co-morbidities and degree of proteinuria^[2]

Supportive measures are to performed in IgA nephropathy similar to the measures required for management of ATN^[2]

• Indication: Remarkable presence of only ATN and intratubular RBC casts

• Angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II-receptor blocker (ARB)^[2]
  • To titrate dosages as required and as tolerated^[2]
  • Duration: Chronic
  • Indications:
    • Proteinuria > 1g/24 hrs in adults or 0.5 g/24 hrs in children
    • Blood pressure > 130/80 mmHg if proteinuria < 1g/24 hrs
    • Blood pressure > 125/75 mm Hg if proteinuria > 1g/24 hrs

ACE-I or ARB are helpful to reduce proteinuria. Nonetheless, randomized clinical trials (RCT) have not yet been conducted to assess their role in reducing the progression to ESRD. Although combination therapy has been proven more effective in monotherapy in some studies^[4][5], KDIGO guidelines have not made recommendations about combination therapy yet pending RCTs.

• Corticosteroids^[2]
  • Duration: 6 months
  • Indication: GFR > 50 ml/min/1.73m2 and persistent proteinuria > 1g/24 hrs despite ACE-I or ARB and BP control

The use of steroids in patient with a GFR<50 ml/min/1.73m2 has not been studied yet. Specific dosage is not yet recommended according to KDIGO guidelines. There are more observed side-effects with high-dose pulse corticosteroids.

• Immunosuppressive agents (cyclophosphamide, azathioprine)^[2]
  • Duration: Cyclophosphamide: 3 months and azathioprine: minimum 2 years.
  • Indication: Patients on steroid therapy with rapidly progressive IgA nephropathy and >50% crescent formation on biopsy

Immunosuppressive agents should not be used in patients with low GFR < 30 ml/min/1.73m2 except if indicated as above. The dose of steroid must be reduced when using concomitant immunosuppressive therapy. One RCT showed better kidney function by reducing corticosteroid dose from 40mg/d to 10mg/d with use of cyclophosphamide at 1.5mg/kg/d for 3 months followed by azathioprine at 1.5mg/kg/d for at least 2 years.

• Fish oil^[2]
  • Indication: Persistent proteinuria > 1g/24 hrs despite 3-6 months of optimal ACE-I or ARB and blood pressure control.

Fish oil at a dose of 12g/d was shown to improve renal outcome in patients with IgA nephropathy in trials by reducing rate of ESRD in 4 years from 40% to only 4%.^[6] In another 6-month study, 3g/d dose also showed better prognosis with less proteinuria.^[7]

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