Predictive Value Of BMI And Monosaccharide Fraction Analysis In The Prognosis Of Patients With IgA Nephropathy

Objective:IgA nephropathy is a major cause of chronic kidney disease and renal failure,and about30%of patients will develop end-stage renal failure after 20 years.The etiology of IgA nephropathy includes immunological,genetic,environmental,nutritional factors.Metabolic syndrome is an important factor in the development of IgAN,and the galactose-deficient IgA1 molecule is thought to be central to the pathogenesis.With the continuous improvement of research methods such as chromatography and mass spectrometry,the glycan structure of IgA molecules has been analyzed,and the hot spots of research have focused on the O-glycans and N-glycans,which have limited their clinical application due to the complex structure.Therefore,the aim of this study is to investigate the predictive value of body mass index and serum monosaccharides in the prognosis of patients with IgA nephropathy.Methods:1.Part 1The clinical data,pathological data and follow-up endpoints of 533 primary IgAN patients who were diagnosed by renal biopsy in the Affiliated Hospital of Qingdao University from February 2013 to May 2021 were retrospectively analyzed[serum creatinine levels doubling and/or entered end-stage renal disease(ERSD)and/or renal replacement therapy],according to the BMI index and WHO obesity classification of the enrolled patients when undergoing renal biopsy,the groups are as follows:low body weight(<18.5kg/m~2),normal body weight(18.5-24.9kg/m~2)and overweight and obesity group(≥25kg/m~2),compare the differences in clinicopathological and prognosis changes of patients in each group.The Kaplan-Meier survival curves were used to assess the cumulative renal survival of the three groups of patients,and multifactorial Cox regression analysis was performed to analyze the risk factors affecting the renal prognosis of overweight and obese patients with IgAN combined.2.Part 2A total of 125 patients diagnosed with primary IgAN by renal biopsy from September2016 to March 2021 in Qingdao University Affiliated Hospital were included in the study.Serum samples,basic clinical laboratory characteristics and detailed pathological information,including age,sex,BMI,and serum creatinine,were collected from all initial admission renal biopsies and during follow-up.Composite endpoints included doubling of creatinine and/or entry into ESRD and/or renal replacement therapy.Serum samples were collected from 125 healthy volunteers with normal renal function,no kidney disease,no other serious diseases and age and sex matched as healthy controls,randomly selected from the same hospital physical examination center.The serum was processed by"PCR-assisted acid degradation"and analyzed by high performance liquid chromatography(HPLC)to compare the expression levels of serum monosaccharides between IgA nephropathy and healthy controls.The correlation between serum monosaccharides and clinical and pathological indicators was analyzed by heat map,and then we used logistic regression to construct a prediction model for serum monosaccharides to investigate the relationship between serum monosaccharide levels and the progression of IgA nephropathy.Results:1.Part 1Among the 533 enrolled IgAN patients,19(3.6%)were in the low-body group,267(50.1%)were in the normal-body group,and 247(46.3%)were in the overweight-obese group.Compared with other groups,age,systolic blood pressure,ACEI/ARB use ratio,diastolic blood pressure,hemoglobin,fasting glucose,uric acid,24-h urinary protein excretion,triglycerides,serum C3,and serum C4 levels were higher in the overweight obese group,while HDL-C and e GFR levels were lower(all P<0.05).Age,systolic blood pressure,diastolic blood pressure,ACEI/ARB ratio,and uric acid were higher in the normal group than in the low group,while e GFR and neutrophil count were lower than in the low group(all P<0.05).Compared with the normal group,the percentage of males and CRP levels were higher in the overweight obese group,while Ig M levels were lower(all P<0.05).LDL-C levels were higher in both the overweight obese group and the normal group than in the low group.The results of light microscopy showed that the degree of vascular damage and the degree of inflammatory cell infiltration were higher in the overweight obese group and the normal group than in the low group(all P<0.05).The Kaplan-Meier survival curve showed that the cumulative kidney survival rate was higher in the normal group(c~2=8.702,P=0.003)than in the overweight group(c~2=4.624,P=0.032),while the cumulative kidney survival rate was higher in the overweight group than in the low group(c~2=4.624,P=0.032).The 5-year renal survival rates were 69.8%,75.6%,and 85.9%in the low-body recombination,overweight-obese group,and normal-body recombination,respectively,and the differences were statistically significant.In patients with IgAN combined with overweight obesity,multifactorial Cox regression analysis showed that urinary protein excretion,hemoglobin,and triglycerides were independent risk factors for the occurrence of renal endpoint events.2.Part 2Compared with healthy controls,serum free mannose,degraded mannose,galactosamine,galactose,and fucose concentrations were significantly higher and degraded glucose,N-acetylglucosamine,and G/M values were lower in IgAN patients.Free mannose and glucose concentrations were positively correlated with systolic blood pressure,body mass index and triglycerides,and free mannose concentration was positively correlated with blood neutrophil/lymphocyte ratio(NLR)and cholesterol.Among the serum degraded monosaccharides,the concentrations of degraded glucose,N-acetylaminoglucosamine and free glucose/free mannose(G/M)were negatively correlated with 24-hour urinary protein levels,while the concentration of degraded Fucose and G/M values were positively correlated with serum albumin levels.The more inflammatory cell infiltration and the higher percentage of crescent formation in the kidney pathology of patients with IgAN,the more severe Lee classification,the lower serum degraded glucose concentration,and the increased level of degraded galactosamine with the increase of serum IgA level.In addition,our results suggested degraded glucose level and free mannose level were independent risk factors for IgAN progression.Conclusions:Compared with normal body weight,IgAN patients with low BMI and high BMI have poor prognosis,and IgAN patients with overweight and obesity have more severe renal pathological vascular damage and inflammatory cell infiltration.Therefore,care needs to be taken to balance lifestyle and weight management in IgAN patients with abnormal BMI.This study describes changes in serum monosaccharide concentrations in IgAN patients and shows that certain circulating serum monosaccharides in IgAN patients are associated with clinicopathological indicators and disease progression,highlighting the importance of further research into the role of serum monosaccharides in the pathogenesis of IgAN.