A kidney biopsy gives doctors a snapshot of damage, but it carries risks. This study asks whether urine can reveal something more useful: whether kidney disease is active now, or quietly leaving lasting scars.

IgA nephropathy is the most common primary kidney-filter disease worldwide, and up to half of patients reach end-stage kidney disease within twenty to thirty years of diagnosis. The immune system's complement process is suggested to play key roles in the disease, which has led to trials of medicines that block it.

But disease activity can vary over time, creating a need for urine tests to guide follow-up and treatment. The study examined a wide range of complement-related proteins in blood and urine at the time of kidney biopsy, then compared them with findings in the kidney, clinical features, and later outcomes.

It also compared these markers between IgA nephropathy and kidney inflammation linked to IgA vasculitis, because little is known about possible differences between the two diseases. The study followed people with IgA nephropathy or IgA vasculitis involving the kidneys, using blood and urine samples stored when each person had a biopsy.

The later outcome was judged by how kidney filtering changed over time, or by a combined outcome of losing half that filtering ability or reaching end-stage kidney disease. Think of the kidney as a house with different kinds of damage: some urine signals appeared more often when the kidney filters showed active swelling and new cell growth.

A different urine signal appeared more often with damage in the kidney's supporting tissue, while higher levels of another signal were found when both filter changes and supporting-tissue damage were present. Among the signals studied, urine C4c was the only one independently linked with a steeper decline in kidney filtering after other measured factors were taken into account.

Urine C4c was also higher among people who later reached the combined outcome, and its link with that outcome remained after accounting for an existing kidney-risk score. This difference was unlikely to be due to chance, with a p-value of zero point zero zero four.

The urine and blood marker levels did not differ significantly between IgA nephropathy and IgA vasculitis involving the kidneys. That result stayed the same when people receiving immune-suppressing treatment at the time of sampling were left out of the comparison. Overall, urine proteins linked to the complement system, particularly PTX-3, MBL, and C4c, might serve as markers of active disease and chronic changes in both conditions.

The results still need confirmation in larger, forward-looking studies, but the goal is practical: because kidney biopsy poses risks, a non-invasive urine marker could help clinicians guide follow-up and improve treatment decisions. The study links different urine signals with different stages of kidney injury: some with active inflammation, and another with longer-term damage.

That could eventually help guide follow-up without relying so often on biopsy.