What is the management of Immunoglobulin A (IgA) nephropathy in hospitalized patients with worsening renal function, also known as Impaired renal function?

From the Guidelines

Hospitalized patients with IgA nephropathy experiencing worsening kidney function should be managed with optimized supportive care, including RAS blockade, blood pressure control, and lifestyle modifications, and considered for a 6-month course of glucocorticoid therapy if proteinuria remains above 0.75-1 g/d despite supportive care. The primary focus of IgA nephropathy management should be multifaceted, optimized supportive care, including RAS blockade as much as tolerated or allowed, blood pressure control, cardiovascular risk minimization, adherence to lifestyle advice, including dietary counselling, smoking cessation, weight control, and exercise as appropriate 1.

Key Considerations

• RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d 1
• Glucocorticoid therapy may be considered for patients with high-risk features, but its use should be cautious due to potential adverse events 1
• Supportive care is essential, including strict blood pressure control with ACE inhibitors or ARBs as first-line agents, fluid and electrolyte management, and temporary dialysis if needed for uremic symptoms or volume overload

Immunotherapy

• Glucocorticoids may be used as a treatment option, but their clinical benefit is not established, and they should be given with extreme caution or avoided entirely in patients with certain conditions, such as eGFR <30 ml/min per 1.73 m2, diabetes, obesity, latent infections, secondary disease, active peptic ulceration, uncontrolled psychiatric disease, or severe osteoporosis 1
• Other immunosuppressive therapies, including azathioprine, cyclophosphamide, calcineurin inhibitors, and rituximab, are not recommended in IgA nephropathy, except in the setting of rapidly progressive IgAN 1

Emerging Therapies

• New therapies, such as sodium-glucose co-transporter-2 inhibitors, sparsentan, atrasentan, hydroxychloroquine, and enteric-coated budesonide, are being evaluated for the treatment of high-risk IgA nephropathy patients 1
• Targeted-release glucocorticoid, budesonide, has shown potential in reducing proteinuria and may be a promising treatment option for IgA nephropathy 1

From the FDA Drug Label

1. 3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see Adverse Reactions (6. 1), Drug Interactions (7.4)].

Management of IgA Nephropathy with Worsening Kidney Function:

• The FDA drug label for lisinopril suggests monitoring renal function periodically in patients treated with the medication.
• Patients with pre-existing renal conditions, such as chronic kidney disease, may be at increased risk of developing acute renal failure on lisinopril.
• Consideration should be given to withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril.
• However, the label does not provide specific guidance on the management of IgA nephropathy with worsening kidney function.
• Therefore, a conservative clinical decision would be to closely monitor renal function and adjust treatment as needed to minimize the risk of further renal deterioration 2.

From the Research

Management of IgA Nephropathy

• The management of IgA nephropathy involves the use of renin-angiotensin system (RAS) blockers, such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) 3, 4, 5, 6.
• The KDIGO Clinical Practice Guideline for Glomerulonephritis recommends long-term ACEi or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug 4.
• A 6-month course of corticosteroid therapy is suggested for patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day 4.
• Immunosuppressants, such as cyclophosphamide and azathioprine, should be reserved for patients with progressive renal insufficiency or with vasculitic lesions on renal biopsy 4.

Treatment Approaches

• Traditional treatments with RAAS inhibitors and newer therapies, such as SGLT2 inhibitors, endothelin receptor antagonists, and delayed release, primarily locally acting enteric corticosteroids, may reduce proteinuria and preserve kidney function 3.
• Non-immunosuppressive options and lifestyle modifications may also slow disease progression 3.
• Emerging therapies, including complement inhibitors and immunomodulators, are currently in clinical trials and offer hope for improving the prognosis of IgAN in the future 3.

Renin-Angiotensin Blockade

• Renin-angiotensin system (RAS) blockade using ACEi/ARB is first-line therapy for IgA nephropathy (IgAN) 5.
• The antiproteinuric effects of ACE inhibitors and ARBs are probably equivalent, and dual ACE inhibitor-ARB therapy reduces proteinuria by 54% to 73% and is more effective than either agent alone 6.
• RAS blockade preserves renal function long-term, and most individuals with proteinuric renal diseases, including IgA nephropathy, should be treated with ACE inhibitors and ARBs, ideally in combination 6.

Predictors of Response to Treatment

• Patients who failed to achieve remission had lower baseline eGFR and serum albumin levels, asymptomatic hyperuricemia, and higher proteinuria 5.
• E1 and T1/T2 lesions were more frequent on histology in patients who failed to achieve remission 5.
• Patients with severe clinical and histological disease were less likely to tolerate and respond to treatment with RAS blockade 5.