Analysis of clinicopathological features and prognosis in children with immunoglobulin A nephropathy accompanied by IgM deposition
Liu Haipeng, Zhu Feng, Zhao Yingrong, et al.
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1.Department of Emergency, Xuzhou Children's Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221000, China; 2.Department of Nephrology, Xuzhou Children's Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221000, China
Objective To investigate the clinical and pathological features and prognosis of children with
immunoglobulin A nephropathy (IgAN) accompanied by IgM deposition. Methods A retrospective study wasconducted. A total of 462 children with primary IgAN, confirmed by renal biopsy at the Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from January 2008 to December 2022 were enrolled as study subjects. Based on the presence or absence of IgM deposition on immunofluorescence examination of renal biopsy, all children were divided into the IgM deposition group (n=243) and the IgM-negative group (n=219). According to the site of IgM deposition, the IgM deposition group was further subclassified into IgM deposition subgroup A (n=185, deposition confined to the mesangial area) and IgM deposition subgroup B (n=58, deposition in both the mesangium and capillary loops). The clinical manifestations, laboratory parameters, renal pathological lesions and prognosis of all children were analyzed. The renal survival rate was estimated using the Kaplan-Meier method. Cox regression models were applied to identify risk factors for progression to end-stage renal disease (ESRD) in IgAN children. Statistical analysis was performed using the t-test, Mann-Whitney U test, and χ2-test. Results The levels of 24-hour urinary protein excretion (24 h UPE), serum creatinine in the IgM deposition group were significantly higher than those in the IgM-negative group [(37.34±7.26) mg/kg vs (22.18±4.48) mg/kg, (70.27±18.94) μmol/L vs (57.42±15.08) μmol/L, with t values of 2.415, 2.976, respectively, all P<0.05], the levels of serum uric acid, serum IgA, serum IgM and urinary N-acetyl-β-D-glucosidase (NAG) in the IgM deposition group were significantly higher than those in the IgM-negative group [474.50 (382.00, 582.50) μmol/L vs 365.50 (294.70, 512.00) μmol/L, 2.87 (0.84, 3.38) g/L vs 1.59 (0.72, 3.77) g/L, 2.21 (1.67, 2.51) g/L vs 1.44 (1.18, 2.42) g/L, 35.57 (15.38, 87.32) U/mmol Cr vs 14.81 (7.35, 63.94) U/mmol Cr, with Z values of -2.538, -5.783, -5.296, -6.564, respectively, all P<0.05]. The proportions of Oxford classification lesions including segmental sclerosis (S1), intracapillary proliferation (E1), renal tubular atrophy/interstitial fibrosis (T1), cellular (CI), as well as glomerular deposition of IgG, complement C1q and C3 in the IgM deposition group were significantly higher than those in the IgM-negative group [40.74% (99/243) vs 26.48% (58/219), 43.62% (106/243) vs 29.68% (65/219), 29.63% (72/243) vs15.98% (35/219), 38.27% (93/243) vs 23.74% (52/219), 55.97% (136/243) vs 37.90% (83/219), 9.88% (24/243) vs 4.11% (9/219), 69.14% (168/243) vs 53.42% (117/219), with χ2 values of 10.436, 9.603, 12.056, 12.288, 15.081, 5.776, 12.031, respectively, all P<0.05]. The IgM deposition group exhibited significantly lower estimated glomerular filtration rate (eGFR), serum C3 levels, and serum IgG levels compared to the IgM-negativegroup [(67.36±14.16) L/（min·1.73 m2) vs (98.19±22.74)mL/（min·1.73 m2), 0.85 (0.56, 1.39) g/L vs1.14 (0.77, 1.63) g/L, 9.14 (7.33, 12.48) g/L vs 11.64 (9.02, 14.71) g/L, t/Z values of 6.142, -3.671, -3.324, respectively, all P< 0.05]. Subgroup analysis further revealed that children in IgM deposition subgroup B exhibited significantly higher levels of 24 h UPE, serum creatinine and urinary NAG [(42.35±8.28) mg/kg vs(31.67±8.05) mg/kg, (68.34±18.91) μmol/L vs (52.87±16.73) μmol/L, (33.78±7.19) U/mmol Cr vs(25.67±6.34) U/mmol Cr, with t values of 2.385, 2.838, 2.603, respectively, all P<0.05], as well as higher proportions of renal S1 and T1 lesions compared with those in IgM deposition subgroup A [58.62% (34/58) vs35.14% (65/185), 46.55% (27/58) vs 24.32% (45/185), with χ2 values of 10.088, 10.463, all P<0.05]. In the IgM deposition group, subgroup B exhibited significantly lower eGFR and serum C3 levels compared to subgroup A [ (45.67±12.36) mL/(min·1.73 m2) vs (53.70±16.67) mL/(min·1.73 m2); 0.72 (0.49, 1.28) g/L vs 0.91 (0.58, 1.34) g/L, with t/Z values of 2.614 and -3.365, respectively, all P< 0.05]. Kaplan-Meier survival curve analysis revealed that the renal survival rate was significantly lower in IgM deposition group compared with IgM negative group (χ2=3.962, P=0.047) , and the renal survival rate was significantly lower in IgM deposition subgroup B compared with IgM deposition subgroup A (χ2=5.392, P=0.020). Multivariate Cox regression analysis showed that eGFR, IgM deposition in the mesangium and capillary wall, S1 and C1/2 were risk factors for the endpoint event in IgAN children. Conclusions Children with IgAN accompanied by IgM deposition manifest more severe proteinuria, more severe renal pathological lesions and worse long-term renal prognosis. IgM deposition in both glomerular mesangium and capillary loops serves as an independent risk factor for poor prognosis in children with IgAN.
2026, Vol. 14 
