When it comes to the treatment of IgA nephropathy, the emphasis is on early intervention. But what exactly does "early" mean in this context? (Single choice)
A. Start treatment immediately once kidney function begins to decline.
B. Begin treatment when proteinuria levels rise significantly above 1.0 grams per day, even if kidney function has not yet declined.
C. Initiate or intensify treatment when proteinuria levels reach or exceed 0.5 grams per day.
On World Kidney Day, March 12th, we focus on kidney health and discuss the optimal timing for treating IgA nephropathy. When should treatment begin, and how should it be managed?
Question 1: Is it too late to start treatment when kidney function just begins to decline?
The answer is clear: it is already too late.
The kidneys have a remarkable reserve capacity, consisting of millions of nephrons. Normally, only a portion of these nephrons are active, which is sufficient to meet the body's needs. When some nephrons become diseased and non-functional, healthy nephrons compensate by working harder. During this phase, even though there may be internal damage, standard kidney function tests may still appear normal. Many early-stage IgA nephropathy patients only discover their condition through routine check-ups, where they might find microscopic hematuria or mild proteinuria, without any noticeable symptoms like edema or fatigue.
However, this apparent stability is deceptive. As the disease progresses, more nephrons fail, and once the compensatory limit is reached, kidney function will rapidly deteriorate. By the time this happens, the damage may already be extensive, and kidney function can decline precipitously.
Therefore, true "early" treatment means intervening before kidney function starts to decline, while the kidneys still have sufficient reserve and the damage is manageable.
Question 2: When should a kidney biopsy be performed for diagnosis?
The answer is that a kidney biopsy should be considered when proteinuria reaches or exceeds 0.5 grams per day.
Proteinuria at or above 0.5 grams per day is a critical threshold indicating the onset of kidney damage. Numerous studies have shown that patients with proteinuria exceeding 0.5 grams per day have a significantly higher risk of developing kidney failure. Early and accurate diagnosis is crucial for initiating targeted treatments, controlling the disease, and delaying the progression to kidney failure.
Kidney biopsy remains the gold standard for diagnosing IgA nephropathy. Many patients present with very mild symptoms, such as slight proteinuria, and without a definitive diagnosis and timely intervention, the best window for treatment may be missed. This underscores the importance of seeking medical evaluation promptly upon detecting elevated proteinuria, rather than waiting for kidney function to decline.
Recommendations from the Chinese Clinical Practice Guidelines for Adult IgA Nephropathy and IgA Vasculitis Nephritis (2025)[1]
Question 3: When should treatment be initiated?
The answer is also when proteinuria reaches or exceeds 0.5 grams per day. Here’s a detailed breakdown:
Which level of proteinuria—1.0 gram per day, 0.5 gram per day, or 0.3 gram per day—should trigger the start of treatment?
The 2025 KDIGO guidelines recommend that for IgA nephropathy patients, treatment or intensified treatment should be considered when proteinuria is ≥0.5 grams per day (or equivalent).
Recommendations from the 2025 KDIGO Guidelines for the Management of IgA Nephropathy and IgA Vasculitis[2]
Why 0.5 grams per day? What do the other thresholds, 1.0 gram per day and 0.3 gram per day, signify?
(1) 1.0 gram per day: A former safety line, now insufficient.
Early research indicated that maintaining proteinuria below 1.0 gram per day could effectively improve outcomes for IgA nephropathy patients, leading to guidelines recommending this as the treatment target. However, recent studies in China and the UK have shown that even with proteinuria controlled between 0.5 and 1.0 grams per day, about 30% of patients still develop kidney failure within ten years[1].
(2) 0.5 gram per day: The true risk threshold.
A large epidemiological study conducted at Peking University First Hospital[4] found that 0.5 grams per day acts as a critical threshold. Below this level, the risk of kidney failure is relatively low; above it, the risk increases significantly. Patients who maintain proteinuria below 0.5 grams per day experience greater long-term kidney protection compared to those with proteinuria between 0.5 and 1.0 grams per day.
(3) 0.3 gram per day: An ideal target for better outcomes.
The same study from Peking University First Hospital also revealed that lower proteinuria levels correlate with a lower risk of kidney failure and a slower decline in estimated glomerular filtration rate (eGFR). Specifically, eGFR declines at a rate of 0.5 mL/min/1.73m² for proteinuria <0.3 grams per day, 0.8 mL/min/1.73m² for 0.3-0.5 grams per day, 1.6 mL/min/1.73m² for 0.5-1.0 grams per day, and 3.3 mL/min/1.73m² for >1.0 grams per day. These data indicate that maintaining proteinuria below 0.3 grams per day or between 0.3 and 0.5 grams per day can effectively prevent kidney failure, with an eGFR decline rate of less than 1 mL/min/1.73m² per year.
While the guidelines recommend 0.3 grams per day as an ideal target for proteinuria control, they do not currently suggest starting treatment based on proteinuria levels above 0.3 grams per day.
Is supportive treatment alone sufficient for early intervention?
IgA nephropathy involves two types of kidney damage:
1. Immune-inflammatory damage: Pathogenic IgA and immune complexes deposit in the kidneys, triggering complement activation and inflammation, leading to kidney destruction.
2. Secondary chronic kidney disease (CKD) damage: After immune-inflammatory damage, some glomeruli become sclerotic and lose function, while the remaining glomeruli work under high pressure and high filtration, leading to further damage and disease progression.
Supportive treatment primarily addresses secondary CKD damage. If only supportive treatment is provided, immune-inflammatory damage will continue. Relying solely on supportive medications (such as angiotensin receptor blockers or ACE inhibitors) to control proteinuria may mask ongoing immune damage, allowing the disease to progress silently.
Therefore, the latest guidelines no longer emphasize starting with supportive treatment and then adding anti-inflammatory and causal treatments after a few months. Instead, they recommend a combined approach of supportive and anti-inflammatory treatments for most progressive cases. The KDIGO guidelines also suggest that all IgA nephropathy patients at risk of progressive kidney function decline should receive nine months of budesonide enteric-coated capsules.
Recommendations from the 2025 KDIGO Guidelines for the Management of IgA Nephropathy and IgA Vasculitis
Summary
For the initiation of treatment in IgA nephropathy, the correct answer to the initial multiple-choice question is now clear:
×A. Waiting until kidney function begins to decline to start treatment is too late.
×B. Starting treatment only when proteinuria exceeds 1.0 grams per day is outdated.
√C. Treatment should begin or be intensified when proteinuria reaches or exceeds 0.5 grams per day—this is the current guideline-recommended threshold.
Upon detecting elevated proteinuria, prompt diagnosis and treatment are essential for protecting kidney function. Early intervention should not rely solely on supportive measures but should also include targeted anti-inflammatory and causal treatments. Combining both approaches offers the best long-term outcomes for IgA nephropathy patients.
References
[1] Chinese Clinical Practice Guidelines for Adult IgA Nephropathy and IgA Vasculitis Nephritis (2025)
[2] 2025 KDIGO Clinical Practice Guideline for the Management of IgA Nephropathy and IgA Vasculitis
[3] 2021 KDIGO Clinical Practice Guideline for Glomerular Diseases
[4] Shen X, Chen P, Liu M, et al. Long-term outcomes of IgA nephropathy in China. Nephrol Dial Transplant. 2025 May 30;40(6):1137-1146.