A total of 1020 participants were included and 895 existing population data were analyzed. The flow chart is shown in Fig. 1. The mean age of all patients was 40.97 ± 12.261 years. There were 384 males (42.9%) and 511 females (57.1%). Baseline HALP value was 39.97 (30.72, 53.25). According to the quartile of HALP scores in the study population, the subjects were divided into four groups: Quartile 1 (< 30.72), Quartile 2 (30.72–39.97), Quartile 3 (39.97–53.25) and Quartile 4 (> 53.25). The findings indicated no statistically significant differences in BMI, systolic blood pressure, diastolic blood pressure, diabetes history, uric acid, low density lipoprotein, immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3 and complement C4 among different HALP groups (P > 0.05). Compared with high HALP group, Quartile 1 (< 30.72 points) were older, had higher levels of platelet count, serum creatinine, triglyceride, cholesterol, high-density lipoprotein and 24 h urinary protein, lower levels of lymphocyte count, hemoglobin, albumin and eGFR, and the proportion of female and hypertension was higher (p < 0.05). The demographic characteristics and clinical parameters are shown in Table 1.
Fig. 1Flowchart showing the number of IgAN patients included in the analyses
Table 1 Baseline data of patients with IgAN in the different HALP score groupAssociations of HALP score with Oxford classificationThere was no significant difference in Mesangial hypercellularity (M) among HALP groups (p > 0.05), while Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), Tubular atrophy/interstitial fibrosis (T) and Cellular or fibro-cellular crescents (C) was statistically significant (P < 0.05). And Quartile 1 (< 30.72) had a higher proportion of E1, S1, T1, T2, and C2. (Table 2). The results showed that patients with different HALP scores had different pathological manifestations, and the Quartile 1 had the most severe pathological changes.
Table 2 Characteristics of Oxford classification in different HALP score groups in the study populationSpearman rank correlation coefficient test was used to further clarify the correlation between HALP and IgAN renal pathological changes, which showed that the correlation between HALP and Mesangial hypercellularity (M) was not statistically significant (p > 0.05), and that with Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), Tubular atrophy/interstitial fibrosis (T), and Cellular or fibro-cellular crescents(C) were statistically significant (p < 0.05). Among them, HALP was negatively correlated with renal tubular atrophy/interstitial fibrosis (T) (correlation coefficient = −0.170, p = 0.000) (Table 3, Fig. 2).
Table 3 Correlation analysis of HALP with Oxford classification in IgANFig. 2Heat matrix of correlation coefficients between HALP and Oxford classification in the study population
Analysis of factors influencing severe tubular atrophy/interstitial fibrosisUnivariate Logistic regression analysis suggested that HALP was a protective factor for severe tubular atrophy/interstitial fibrosis in IgAN. Among the HALP subgroup variables, the risk rate of severe tubular atrophy/interstitial fibrosis decreased by 92.3% in Quartile 2 (OR = 0.077, 95 CI 0.046–0.128, p = 0.000), 96.3% in Quartile 3 (OR = 0.037, 95 CI 0.018–0.075, p = 0.000), using Quartile 1 as the control group, and a 96.8% decrease in Quartile 4 risk rate (OR = 0.032, 95 CI 0.015–0.069, p = 0.000). In addition to HALP, age, BMI, gender, systolic blood pressure, diastolic blood pressure, hypertensive disease, diabetes mellitus, 24 h urine protein quantification, eGFR, uric acid, blood lipids, immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3, complement C4, thylakoid hyperplasia (M), endocapillary hyperplasia (E), segmental sclerosis (S), and crescentic bodies (C) were all relevant T2 influencing factors.
After adjusting for covariates, multifactorial Logistic regression analysis revealed that HALP was an independent influence on the incidence of severe tubular atrophy/interstitial fibrosis in IgAN. The continuous variable HALP was associated with a 4.8% reduction in the incidence of severe tubular atrophy/interstitial fibrosis in IgAN patients for each 1-unit increase in HALP (OR = 0.952, 95 CI 0.923–0.972, p = 0.002). We also found that hypertensive disease, eGFR, uric acid, and complement C3 were also independent influences on severe tubular atrophy/interstitial fibrosis in IgAN patients (Table 4).
Table 4 Analysis of factors influencing severe tubular atrophy/interstitial fibrosis in 895 IgAN (logistic regression)In fact, it can be seen in Table 4 that continuous HALP is an independent influencing factor for severe tubular atrophy/interstitial fibrosis. In categories HALP, compared with Quartile1, Quartile3 and Quartile4 are independent influencing factors for severe tubular atrophy/interstitial fibrosis, except Quartile2. Combined with baseline data, this may be related to patients in Quartile2 being younger, less male, less hypertensive, lower creatinine, and lower uric acid.
Curvilinear relationship between HALP and severe tubular atrophy/interstitial fibrosisRestricted cubic splines revealed that there was a linear correlation between HALP and. T2 (P for non-linearity = 0.896), showing a trend that low HALP values are positively correlated with a high risk rate for the development of severe renal tubular atrophy/interstitial fibrosis (Fig. 3).
Fig. 3Curvilinear relationship between HALP score and risk of severe tubular atrophy/interstitial fibrosis
Value of HALP in predicting severe tubular atrophy/interstitial fibrosisThe above results indicate that HALP is an independent influence on the incidence of severe tubular atrophy/interstitial fibrosis in IgAN. The predictive value of HALP for the occurrence of severe tubular atrophy/interstitial fibrosis was further clarified by plotting the subjects' work characteristic curve (ROC). The results suggested that HALP predicted severe tubular atrophy/interstitial fibrosis with an area under the ROC curve of 0.693, an optimal critical value of 36.54 for HALP score, a specificity of 0.619, a sensitivity of 0.705, and a Youden index of 0.324 (Fig. 4).The ROC curve suggests that elevating the value of HALP above 36.54 may help patients maintain a good renal prognosis.
Fig. 4ROC curve for HALP score to predict severe tubular atrophy/interstitial fibrosis
Meanwhile, the AUC value for continuous HALP predicted a severe outcome is 0.693, less than albumin and serum creatinine. However, the combination of HALP may have a better predictive value for severe outcome than albumin (serum creatinine) alone, as shown in Fig. 4.
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