Clinicopathological Characteristics And Prognostic Analysis Of Serum IgA/lymphocyte Count In IgA Nephropathy

BackgroundIgA nephropathy(IgAN)is an immune-related disease with heterogeneous clinical manifestations and disease progression.The diagnosis mainly depends on renal biopsy.The pathological feature is the deposition of IgA with complement C3 in glomerular mesangial region.It was first proposed by French scholar Berger and also known as Berger’s disease.The disease has become one of the most common primary glomerular diseases leading to end-stage renal disease(ESRD).At present,the pathogenesis of IgAN is not completely clear.The generally recognized pathogenesis of IgAN is the "four-hit theory".Due to genetic or environmental factors and other factors,galactose deficiency IgAl(Gd-IgAl)is produced automatically,followed by induction of specific IgG antibodies,and the hinge region of Gd-IgAl binds to specific IgG antibodies to form Gd-IgAl-IgG immune complexes,which deposit in the glomerular mesangial region and can cause a "waterfall" inflammatory response resulting in kidney injury.Based on this theory,serum Gd-IgAl has been confirmed as a biomarker for predicting the prognosis of patients with IgAN.Because the detection of serum Gd-IgA1 is difficult and expensive,it cannot be extended to underdeveloped areas and grass-roots units for application.We expect to find new simple,reliable,non-invasive and affordable indicators.Compared with the detection of serum Gd-IgA1,the detection of serum IgA has lower technical requirements and cheaper cost and can be popularized in a wider area.In this study,the serum IgA level,which is more easily obtained in clinic,was corrected by serum lymphocyte count to analyze the change and significance of serum IgA/lymphocyte count in IgAN.PurposeTo study the clinicopathological characteristics and prognostic value of serum IgA/lymphocyte count in patients with IgAN,and to explore the independent risk factors affecting the progression of IgAN patients to ESRD,and to construct a prediction model to assess the specific contribution of different independent risk factors to predicting the prognosis of IgAN patients.MethodsThe data of 306 patients diagnosed with primary IgAN by renal biopsy in the First Affiliated Hospital of Zhengzhou University from January 1,2014 to January 1,2020,with baseline serum IgA level,and followed up for more than 3 months were collected.The median of serum IgA/lymphocyte count(M=1.436)was used for grouping,and the differences in clinicopathological data and treatment regimens such as gender,age,blood pressure,cystatin C,blood urea nitrogen,serum creatinine,blood uric acid,estimated glomerular filtration rate(eGFR),serum albumin,cholesterol,triglycerides,urine red blood cell count,24-hour urinary protein quantification,white blood cell count,red blood cell count,hemoglobin,platelet count,lymphocyte count,monocyte count,eosinophil count,serum immunoglobulin(serum IgG,serum IgM,serum IgA),serum complement C3,serum complement C4,CD3+T lymphocyte count,CD4+T lymphocyte count,CD8+T lymphocyte count,Th/Ts,electrolytes(potassium,sodium,chloride,calcium,phosphorus,magnesium),carbon dioxide binding capacity,light microscopy,electron microscopy,and immunohistochemistry of renal tissue were compared between the high and low groups.The survival curves of kidney were drawn by Kaplan-Meier method,and the differences were tested by Log-rank.Univariate and multivariate analysis were performed using Cox proportional hazards regression models to study the independent risk factors affecting the prognosis of patients with IgAN.A nomogram predicting 6-month,1-year,and 2-year progression-free to ESRD survival in IgAN patients was constructed according to the independent risk factors affecting prognosis,and the predictive discrimination of the nomogram and the consistency of the prediction model with the actual results were determined by the concordance index(C-index)and calibration curve.Results(1)A total of 306 patients with primary IgAN were included in this study,including 170 males(55.6%),the mean age was 40±12 years old.The median of serum IgA/lymphocyte count was 1.436,153 in the low serum IgA/lymphocyte count group and 153 in the high serum IgA/lymphocyte count group.In the general data and common laboratory indexes,compared with the low serum IgA/lymphocyte count group,the patients in the high serum IgA/lymphocyte group were older,and the white blood cell count,red blood cell count,platelet count,lymphocyte count,hemoglobin,cholesterol,carbon dioxide binding capacity were lower,the differences were statistically significant(P<0.05).(2)Among the inflammatory indexes,compared with the low serum IgA/lymphocyte count group,the patients in the high serum IgA/lymphocyte count had higher serum IgG and serum IgA,and lower CD3+T lymphocyte count,CD4+T lymphocyte count and CD8+T lymphocyte count,the differences were statistically significant(P<0.05).Among the pathological characteristics,there was no statistically significant difference in the new Oxford classification of patients in different serum IgA/lymphocyte count groups(P>0.05),but the complement C3 deposition rate of patients in the high serum IgA/lymphocyte count group was significantly higher than that in the low serum IgA/lymphocyte count group(P<0.05).(3)In this study,the follow-up began with the date of renal biopsy,and the follow-up time ranged from 3 to 76 months.The median follow-up time was 15(8,26)months.Of the 306 patients with primary IgAN,71(23.2%)patients entered the terminal event,and 53(17.3%)patients progressed to ESRD.Of the 153 patients in the high serum IgA/lymphocyte count group,45(29.4%)patients entered the terminal event and 35(22.9%)patients progressed to ESRD.The survival curve analysis of patients entering the terminal event in the two groups showed that the cumulative renal survival rate of patients in the high serum IgA/lymphocyte count group was lower than that of patients in the low serum IgA/lymphocyte count group(χ2=6.621,P=0.01).(4)Univariate and multivariate Cox regression analysis showed that when serum IgA/lymphocyte count was used as a grouping variable(assignment:low serum IgA/lymphocyte count group=1,high serum IgA/lymphocyte count group=2),in univariate Cox regression analysis,high serum IgA/lymphocyte count was associated with progression to ESRD in IgAN patients(HR=1.868,95%CI:1.057-3.301,P=0.031),and in multivariate Cox regression analysis,serum IgA/lymphocyte count was an independent risk factor affecting progression to ESRD in IgAN patients(HR=2.848,95%CI:1.516-5.348,P<0.001);when serum IgA/lymphocyte count was used as a continuous variable,it also showed that high serum IgA/lymphocyte count was associated with progression to ESRD in IgAN patients(HR=1.221,95%CI:1.030-1.447,P=0.021),in multivariate Cox regression analysis,serum IgA/lymphocyte count was still an independent risk factor affecting progression to ESRD in IgAN patients(HR=1.596,95%CI:1.306-1.950,P<0.001).(5)When serum IgA/lymphocyte count was used as a grouping variable and continuous variable,respectively,the C-index internally validated by the nomogram prediction model for 6-month,1-year,and 2-year progression-free to ESRD survival rates in IgAN patients was 0.905(95%CI:0.868-0.942)and 0.917(95%CI:0.882-0.952),respectively,indicating that the nomogram prediction model had high discrimination.In addition,the calibration curves showed good agreement between the prediction model and the actual results.ConclusionIgAN patients with high serum IgA/lymphocyte count had more severe clinical manifestations and renal pathological changes,lower renal cumulative survival rate.Serum IgA/lymphocyte count was an independent risk factor for progression to ESRD in IgAN patients,and it has a high contribution to predicting the prognosis of IgAN patients.The results of this study suggest that this ratio can be used as a simple and affordable indicator to provide a reference for assessing the prognosis of IgAN patients and formulating individualized treatment plans.