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A UK registry analysis of 1,416 kidney transplant recipients found recurrent IgA nephropathy was associated with a 2.5- to 3.5-fold higher risk of graft failure. Proteinuria often rose years before recurrence was diagnosed, but the study does not establish that earlier detection or treatment would prevent graft loss.
A study of 1,416 kidney transplant recipients in the U.K. found that recurrent IgA nephropathy was associated with a 2.5- to 3.5-fold higher risk of graft failure, with urine protein levels often increasing years before recurrence was diagnosed. The registry analysis, presented at the American Society of Nephrology Kidney Week meeting, also found that higher proteinuria when recurrence was identified was linked to poorer graft outcomes.
Researchers examined recipients who had a first kidney transplant for biopsy-proven IgA nephropathy at 37 centers between 2000 and 2025. During a median follow-up of nine years, recurrence was diagnosed in 244 recipients: a cumulative incidence of 24%, with a median 4.8 years from transplant to diagnosis. The analysis found median death-censored graft survival fell to just over four years after recurrence.
The team reported that the original kidney disease appeared more aggressive among recipients who later had recurrence: before transplantation, their native-kidney function declined more quickly than in recipients without documented recurrence. In models starting one year after transplant, older age at kidney failure and maintenance prednisolone use were associated with lower recurrence risk. Prednisolone use was associated with a 40% reduction in risk, but the observational analysis cannot establish that the medication caused the difference.
Proteinuria measurements also differed well before diagnosis. By year six after transplant, the model-predicted urine protein-creatinine ratio was 0.89 g/g among recipients who later developed recurrence and 0.17 g/g among those who did not. At year 11, the estimates were 4.56 g/g and 0.25 g/g, respectively. A doubling of the ratio before diagnosis was associated with a 2.2-fold higher risk of graft failure.
Proteinuria May Precede Recurrence
The findings identify a long period in which protein levels may rise before clinicians diagnose recurrent disease, alongside a strong association between recurrence and loss of the transplanted kidney. That pattern could help researchers investigate whether monitoring changes or earlier evaluation might identify people at higher risk. The study does not show that acting on proteinuria earlier would prevent recurrence or improve graft survival.
At the time recurrence was diagnosed, even moderate proteinuria was associated with poor outcomes. The researchers estimated a 50% cumulative incidence of graft failure at five years for patients with a urine protein-creatinine ratio of 0.5 to 1.0 g/g; the estimate was 70% for those above 1.0 g/g. These are study estimates for the analyzed group, not individual predictions.
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Recurrence After Kidney Transplant
IgA nephropathy is an immune-related kidney disease that can progress to kidney failure. A transplant replaces a failed kidney but does not necessarily prevent the underlying disease from returning in the transplanted organ. The report says about 20% to 40% of people with IgA nephropathy develop end-stage kidney disease within 20 years of diagnosis.
The analysis used the U.K. National Registry of Rare Kidney Diseases, known as RaDaR, to characterize recurrence and graft outcomes. The cohort was predominantly white (84%), had a median age of 45, and included 27% women; 46% received a kidney from a living donor. The results therefore describe this study population and may not apply equally to all transplant recipients.
“Proteinuria trajectories are rising many years before we’re actually making the [biopsy] diagnosis.”
— Sherry Masoud, University College London, lead researcher
Limits of the Registry Findings
The findings are observational: they show associations, not proof that recurrence, proteinuria, or prednisolone use directly caused the reported outcomes. The report does not establish whether closer monitoring or treatment before biopsy diagnosis would change graft survival, nor does it identify a specific intervention that prevents recurrence.
It is also unclear how well the estimates apply beyond the U.K. cohort, which was drawn from 37 centers and was predominantly white. The source does not provide detailed results for all possible differences in care, treatment, or patient characteristics that could affect recurrence and graft failure. The reported recurrence rate and outcome estimates should be read within the study’s follow-up and population.
Further Work on Earlier Detection
The reported next step is research into whether the rising proteinuria seen before diagnosis can support earlier identification of recurrence and whether intervention at that stage changes outcomes. The source does not describe a planned trial, a new clinical guideline, or a scheduled follow-up analysis. For now, the registry results add evidence about recurrence patterns and risk associations but do not set out a new standard of care.
Key Questions
How often did IgA nephropathy recur in this study?
Recurrence was diagnosed in 244 of 1,416 recipients, corresponding to a cumulative incidence of 24% during the study’s follow-up. The median time to diagnosis was 4.8 years after transplant.
What did recurrence mean for the transplanted kidney?
Recurrence was associated with a 2.5- to 3.5-fold higher risk of graft failure. The researchers reported median death-censored graft survival of just over four years following recurrence; this is a group-level estimate, not a prediction for an individual.
Did proteinuria rise before recurrence was diagnosed?
Yes. In the study’s models, urine protein-creatinine ratios began rising years before clinical diagnosis among recipients who later had recurrence. A doubling before diagnosis was associated with a 2.2-fold higher risk of graft failure.
Does the study prove that prednisolone prevents recurrence?
No. Maintenance prednisolone use at one year after transplant was associated with a 40% lower recurrence risk, but the observational study cannot establish that the medication caused the reduction.
Does rising proteinuria mean recurrence is certain?
No. The study found a group-level pattern, not a diagnostic rule. It does not show that every recipient with rising proteinuria has recurrent IgA nephropathy or that earlier detection would prevent graft failure.
Source: medpagetoday.com
