Glomerular IgM Deposit Intensity Shows Clinical Significance in IgA Nephropathy

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Findings from a recent study are providing clinicians with an overview of the value of glomerular IgM deposit intensity in patients with IgA nephropathy (IgAN).¹

Although results showed similar prognosis between patients with positive and negative IgM deposits, in those with positive IgM deposits, increased intensity of these deposits contributed to adverse clinicopathologic presentation and clinical outcomes.¹

A leading cause of glomerulonephritis and renal failure, IgAN is characterized by the deposition of IgA in the glomerular mesangium resulting from abnormal immune reactions. Its clinical presentation varies greatly and progression is typically gradual, but an estimated 20% to 50% of affected patients develop end-stage renal disease within 20 years of diagnosis.² A lack of concrete understanding of the pathological manifestations of IgAN complicates the prediction of prognosis and the efficacy of therapy, underscoring the need for a better understanding of potential influencing factors like IgM deposition.¹

“The significance of glomerular IgM deposit intensity in IgAN remains ambiguous and requires further research,” Ziyuan Huang, of the department of nephrology at the First Affiliated Hospital of Ningbo University in China, and colleagues wrote.¹

To explore the clinical significance and prognostic influence of glomerular IgM deposits and their intensity, investigators conducted a retrospective, single-center study of patients with biopsy-proved IgAN from January 2018 to May 2023. For inclusion, patients were required to have a follow-up duration of > 6 months after renal biopsy; renal biopsy ≥8 glomeruli; and availability of complete clinicopathological data.¹

During the study period, investigators identified 1101 biopsy-proven primary IgAN cases at their center. However, 119 patients were excluded due to short follow-up time, inadequate data, or insufficient glomerular count. The remaining 982 cases were enrolled in the study and divided into 2 cohorts based on the presence or absence of glomerular IgM deposits on the mesangial cells: IgM + (n = 539) and IgM- ( n = 443).¹

After propensity score matching the groups while accounting for gender, age, follow-up time, and estimated glomerular filtration rate (eGFR), investigators noted the IgM + cohort had significantly decreased levels of median albumin (P = .04) and high-density lipoprotein-cholesterol (P = .04) but increased median serum IgG (P = .04). Additionally, the immunofluorescence intensities of glomerular IgA (P <.01), IgG (P = .02), and C3 (P <.01) deposits in the IgM + were significantly stronger.¹

Investigators further stratified patients in the IgM + cohort based on immunofluorescence intensity of IgM deposits, classifying those who exceeded 1+ as the IgM-H cohort (n = 273) and those who were equal to 1+ as the IgM-L cohort (n = 266). After propensity score matching the IgM-H cohort with the IgM-L cohort, investigators noted the IgM-H group displayed increased levels of median systemic immune-inflammation index (P <.01); serum IgM (P <.01); serum IgG (P <.01); serum C4 (P = .03); 24h-UP (P = .02); urine albumin-to-creatinine ratio (UACR) (P <.01); and time-averaged UACR (P <.01), while the median systolic blood pressure (P <.01); diastolic blood pressure (P <.01); Alb (P = .04); and low-dentsity lipoprotein-cholesterol (P <.01) were significantly decreased. Investigators also pointed out the IgM-H group exhibited an increased proportion of E1 (P = .02) and S1 (P = .02) but a decreased proportion of M1 (P <.01), and immunofluorescence results showed the intensities of IgA (P <.01) and C3 (P = .03) deposits were stronger in the IgM-H group.¹

Kaplan–Meier analysis showed no obvious differences in the survival rate between the IgM + and IgM- cohorts (Log-rank, P = .27), suggesting IgM deposit did not contribute to adverse outcomes. However, the Kaplan–Meier curve showed a lower survival rate in the IgM-H cohort compared to the IgM-L cohort (Log-rank, P = .02). In multivariate Cox regression analysis, weaker immunofluorescence intensity of IgM deposition (P = .03) was identified as an independent protective factor, while increased mean arterial pressure (P <.01), increased serum creatinine (P <.01), and increased time-averaged UACR (P <.01) were identified as independent risk factors.¹

“Our research offered further findings on the clinical significance of glomerular IgM deposits in patients with IgAN,” investigators concluded.¹ “Notably, the prognosis of IgM + was not markedly worse compared to IgM–. In IgAN patients with positive IgM deposits, however, increased intensity of glomerular IgM deposits may contribute adversely to clinicopathologic presentation and the outcome.”

References

1. ^{Huang Z, Xu J, Ma J, et al. Clinical significance of glomerular IgM deposit in IgA nephropathy: a 5-year follow-up study. Renal Failure. https://doi.org/10.1080/0886022X.2024.2386146}
2. ^{Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. April 22, 2024. Accessed August 13, 2024. https://www.ncbi.nlm.nih.gov/books/NBK538214}