Risk Factors for IgA Nephropathy Recurrence After Kidney Transplant

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Findings from a recent systematic review and meta-analysis are providing clinicians with an overview of risk factors for immunoglobulin A nephropathy (IgAN) recurrence and subsequent outcomes in patients who received a kidney transplant.

Younger age at the time of kidney transplantation, shorter duration of time from IgAN diagnosis to end-stage renal disease, and less time spent on dialysis were linked to IgAN recurrence, which was associated with poorer graft survival but did not impact post-transplant death or infection rates.¹

“The identification of risk factors for IgAN recurrence is crucial in pre-transplant evaluation, and many studies have been conducted to investigate this issue. However, the results are inconsistent, with some studies indicated that younger age, high human leukocyte-antigen matching, and related donor are risk factors, while others found no significant association,” wrote investigators.¹ “To date, no studies have systematically evaluated the risk factors for IgAN recurrence after kidney transplantation.”

A chronic kidney disease inhibiting the kidney’s filtration process, IgAN can cause loss of kidney function and in some cases total kidney failure. The main goal of treatment is to prevent the need for dialysis or kidney transplantation, although either option may eventually be necessary. Even after receiving a transplant, some patients may experience recurring IgA deposits causing IgAN, but the causes and outcomes of recurrence after transplantation are not well understood.^2,3

To assess risk factors and outcomes for IgAN recurrence, Turun Song, MD, associate faculty at Sichuan University in China, and colleagues searched PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM for relevant studies reporting risk factors or outcomes for IgAN recurrence.¹

For inclusion, studies were required to involve patients who received a kidney transplant due to IgAN-induced renal failure, report on potential risk factors for IgAN recurrence, detail IgAN recurrence in kidney allografts, and be a prospective/retrospective cohort study or case-control study. Eligible studies were limited to those written in English or Chinese.¹

The initial search yielded 8077 studies, of which 2787 duplicates were removed. Investigators then independently screened all relevant titles and abstracts of retrieved publications, applying the inclusion and exclusion criteria to the full-text screening. In total, 58 studies were included in the systematic review and meta-analysis. For each study, investigators extracted the name of the first author, year of publication, location, research design, demographic characteristics, inclusion and exclusion criteria, follow-up time, and effect of recurrence on outcomes.¹

All 58 studies were published between 1984 and 2022 with sample sizes ranging from 13 to 2501. The majority of studies were retrospective cohort studies (n = 56) and were conducted in Asia (n = 23) or Europe (n = 22).¹

Compared to the non-recurrence group, those with IgAN recurrence were younger (Mean difference [MD], -4.27 years; Risk ratio [RR], 0.96; 95% Confidence interval [CI], -5.76 to -2.78) at kidney transplantation. Investigators noted the risk of recurrence decreased by 4% for each 1-year age increase at the time of kidney transplantation (RR, 0.96; 95% CI, 0.95 to 0.97; I² = 29.30%).¹

Additionally, the donor age was also found to be younger in the recurrent group (MD, -2.19 years; 95% CI, -3.46 to -0.93; I² = 34.70%), but the pooled RR of 389 participants from 3 studies was not significant (RR, 0.99; 95% CI, 0.97 to 1.01; I² = 0.00%). Of note, there was no difference in the risk of recurrence among recipients with living donors compared to those with deceased donors (RR, 1.02; 95% CI, 0.90 to 1.14; I² = 48.80%).¹

Although the age at diagnosis of IgAN did not differ between the groups, time from IgAN diagnosis to ESRD was shorter in the recurrence group compared to the non-recurrence group (MD, -1.84 years; 95% CI, -2.43 to -1.25; I² = 0.00%). Further analysis revealed each additional year was associated with a 6% reduction in recurrence (RR, 0.94; 95% CI, 0.91 to 0.97; I² = 0.00%), suggesting suggests patients with a faster progression of primary disease were more susceptible to recurrence.¹

Investigators pointed out patients who experienced IgAN recurrence spent less time on dialysis (MD, -3.14 months) and had lower human leukocyte-antigen (HLA) (MD, -0.11) and HLA-DR mismatches (MD, -0.13). Patients with a history of kidney transplantation had a 43% increased risk of recurrence compared to patients receiving their first kidney transplant (RR, 1.43; 95% CI, 1.24 to 1.65; I² = 47.40%). Patients without induction therapy were also at a greater risk of recurrence (RR, 1.73; 95% CI, 1.16 to 2.58; I² = 70.50%).¹

Investigators assessed 27 studies to determine the RR for graft loss in patients with IgAN recurrence, ultimately finding that it was associated with poorer graft survival (RR, 2.19; 95% CI, 1.60 to 3.01; I² = 82.80%) but did not impact post-transplant death or infection rates.¹

“As patients with recurrence had poor graft outcomes, our findings may improve pre-transplant evaluation of individuals with IgAN-induced renal failure. By properly stratifying risk and implementing appropriate interventions, it might be of help to enhance long-term outcomes in this population,” investigators concluded.¹

References:

1. Li Y, Tang Y, Lin T, Song T. Risk factors and outcomes of IgA nephropathy recurrence after kidney transplantation: a systematic review and meta-analysis. Front Immunol. 2023;14:1277017. doi:10.3389/fimmu.2023.1277017
2. Mayo Clinic. IgA Nephropathy (Berger Disease). Diseases & Conditions. June 9, 2023. Accessed January 9, 2024. https://www.mayoclinic.org/diseases-conditions/iga-nephropathy/diagnosis-treatment/drc-20352274
3. Uffing A, Pérez-Saéz MJ, Jouve T, et al. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin J Am Soc Nephrol. 2021;16(8):1247-1255. doi:10.2215/CJN.00910121