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A systematic review and meta-analysis of 23 studies found that people with IgA nephropathy and proteinuria of 0.5–1.0 g/day had a higher risk of adverse kidney outcomes than those below 0.5 g/day. The observational findings support the stricter proteinuria target in updated KDIGO guidance, but do not prove that treating patients to reach it improves outcomes.
A systematic review and meta-analysis found that proteinuria of 0.5–1.0 g/day is associated with a higher risk of adverse kidney outcomes in people with IgA nephropathy than levels below 0.5 g/day. The findings support the stricter proteinuria target in the 2025 KDIGO guidelines, but the observational evidence does not establish that treatment to reach that target prevents kidney decline.
The review, published in the Clinical Journal of the American Society of Nephrology, combined results from 23 studies involving 15,289 patients in Asia, Europe and North America. Follow-up periods ranged from 3.1 years to more than nine years. The researchers assessed both proteinuria measured at baseline and time-averaged proteinuria, which reflects levels over follow-up.
Across nine studies, baseline proteinuria between 0.5 and 1.0 g/day was associated with a 73% higher risk of adverse kidney outcomes than proteinuria below 0.5 g/day. The pooled hazard ratio was 1.73 (95% confidence interval 1.36–2.20). In seven studies assessing time-averaged proteinuria, low-grade levels were linked to nearly three times the risk (pooled hazard ratio 2.87, 95% CI 1.48–5.56).
Adverse outcomes included a doubling of serum creatinine, a decline in estimated glomerular filtration rate (eGFR) of 30% to 50% or more, kidney failure, or the need for kidney replacement therapy. In four studies, low-grade time-averaged proteinuria was also associated with a faster annual fall in eGFR: a mean difference of −1.02 mL/min/1.73 m² per year compared with lower proteinuria.
Why the 0.5 g/day Target Matters
The findings challenge the long-standing assumption that proteinuria below 1.0 g/day is generally reassuring in IgA nephropathy. They add evidence that risk is present below that older threshold, and that sustained proteinuria levels may help identify patients whose kidney function needs close attention.
The study authors said the results reinforce the 2025 KDIGO recommendation to aim for proteinuria below 0.5 g/day. That target may affect how clinicians discuss risk and monitor patients. However, an association between proteinuria and outcomes does not show that lowering proteinuria to a particular level will itself prevent progression. Treatment decisions still depend on clinical judgment and evidence for specific therapies.
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How Guidance Shifted Below 1 g/day
IgA nephropathy is the most common primary glomerulonephritis worldwide. The source report says up to 50% of patients may progress to kidney failure within 10 to 20 years. Proteinuria, the presence of excess protein in urine, is used as an indicator of kidney damage and a marker of risk in the disease.
Earlier practice commonly treated levels below 1.0 g/day as relatively low risk. The 2025 KDIGO guideline update lowered its proteinuria target from less than 1.0 g/day to less than 0.5 g/day. The review authors said previous recommendations were based mainly on individual observational studies and narrative reviews; their analysis specifically examined the association between low-grade proteinuria and kidney outcomes.
“Low-grade proteinuria should not be dismissed as reassuring in IgA nephropathy.”
— Takaya Sasaki, MD, PhD, of Jikei University School of Medicine, speaking to MedPage Today
Treatment Benefit Remains Unproven
The analysis combined observational studies, so it can show that lower-grade proteinuria is associated with risk but cannot establish that reducing it below 0.5 g/day will improve kidney outcomes. The study author said further research is needed to determine which treatments may help, and when they should be used.
Trial access is another unresolved issue. The report says recent clinical trials have almost exclusively enrolled people with proteinuria above 1.0 g/day. That may leave patients in the 0.5–1.0 g/day range underrepresented in evidence for newer disease-modifying therapies. The review does not determine which of these patients would benefit from treatment or how large any benefit might be.
Trials Must Include Lower Proteinuria
The researchers and editorialists called for interventional trials that enroll patients with low-grade proteinuria. Such studies would need to test whether specific treatments that suppress proteinuria, and the timing of those treatments, translate into better long-term kidney outcomes.
Until those results are available, the review offers evidence to inform risk assessment and supports the updated guideline target, but it does not settle treatment choices for individual patients. The supplied report does not identify a particular upcoming trial or a date for new results.
Key Questions
What counts as low-grade proteinuria in this study?
The review defined low-grade proteinuria as 0.5 to 1.0 g/day. It compared that range with proteinuria below 0.5 g/day.
What kidney outcomes were assessed?
The analysis included a doubling of serum creatinine, an eGFR decline of 30% to 50% or more, kidney failure, or the need for kidney replacement therapy.
Does the study prove that lowering proteinuria prevents kidney damage?
No. The studies were observational, so the results show an association, not proof that treatment to lower proteinuria causes better kidney outcomes.
How does the finding relate to current guidance?
The results support the 2025 KDIGO target of proteinuria below 0.5 g/day, which is lower than the previous target of less than 1.0 g/day. The evidence does not, by itself, determine which treatment is appropriate for a patient.
Why are more clinical trials needed?
Trials have generally enrolled people with proteinuria above 1.0 g/day, according to the report. Studies that include patients with levels of 0.5–1.0 g/day are needed to test whether treatments benefit this group.
Source: medpagetoday.com
