| Objective: In this study,the expression levels of Klotho protein,interleukin-6(IL-6),Wilms tumor protein(WT1)in kidney tissues and urine Klotho protein were detected to investigate the role of Klotho protein in podocyte and tubule interstitial of IgA nephropathy(IgAN).Methods: Forty-four patients with primary IgAN diagnosed by renal puncture for the first time in the Department of Nephrology of our hospital from 2017 to 2019 were collected.Eighteen healthy volunteers from our health check-up center were collected as the control group.Ten renal tissue specimens at the lesion were used as the normal tissue control group.The gender,age,blood pressure,serum creatinine,albumin,24-hour urine protein quantification,and urinary osmotic pressure of the above subjects were collected and the estimated glomerular filtration rate(e GFR)was estimated according to the CKD-EPI formula.According to the Oxford classification of IgA nephropathy,the patients’ tubular interstitial lesions were divided into T0,T1,and T2 groups.Immunohistochemistry(SP)method was used to detect the expression of WT1,IL-6,and Klotho proteins in renal tissues.Enzyme-linked immunosorbent assay(ELISA))Method to determine the concentration of Klotho protein in urine samples.Through collating data and statistical analysis,the role of Klotho protein in podocyte and tubule interstitial of IgAN was explored.Results: 1.Difference analysis:(1)Comparison between IgAN patients and the normal control group: there were statistical differences in urine Klotho and systolic blood pressure between the two groups(P <0.05),and significant differences in albumin,blood creatinine,e GFR,and diastolic blood pressure(P <0.01);(2)Comparison among three groups of IgAN patients: T1 and T0 groups: there were statistically significant differences in the average optical density of renal tissue WT1,glomerular sclerosis,and renal tubular atrophy/interstitial fibrosis(P<0.05);T2 and T0 groups: there were statistically significant differences in renal tissue values of Klotho,IL-6,WT1 average optical density,mesangial hyperplasia,glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,urine Klotho,e GFR,serum creatinine,albumin,urine protein and urine osmotic pressure(P<0.05);T2 and T1 groups: there were statistically significant differences in the mean optical density of renal tissue WT1,renal tubular atrophy/interstitial fibrosis,blood creatinine,e GFR,urine osmotic pressure and urine protein(P<0.05).2.Correlation analysis:(1)Correlation between Klotho of renal tissue and pathology and clinical indicators in IgAN patients: IgAN renal tissue Klotho was negatively correlated with IL-6,mesangial hyperplasia,glomerular sclerosis,renal tubular atrophy/interstitial fibrosis,and serum creatinine(r =-0.484,r =-0.401,r =-0.452,r =-0.412,r =-0.501,P = 0.001,P = 0.007,P = 0.002,P = 0.006,P = 0.001),and positively correlated with WT1,urine Klotho,e GFR(r = 0.566,r = 0.374,r = 0.437,P <0.001,P = 0.012,P = 0.003);(2)Correlation between IL-6 of renal tissue and pathological and clinical indicators in IgAN patients: there was a negative correlation between the level of renal tissue IL-6 and renal tissue Klotho,WT1 and e GFR in IgAN patients(r =-0.484,r =-0.738,r =-0.447,P = 0.001,P <0.001,P=0.002),and a postive correlation with mesangial hyperplasia,glomerular sclerosis,renal tubular atrophy/interstitial fibrosis,blood creatinine and urine protein(r = 0.324,r = 0.329,r = 0.402,r = 0.550,r = 0.479,P = 0.032,P = 0.029,P = 0.007,P <0.001,P = 0.001);(3)Correlation between WT1 of renal tissue and pathological and clinical indicators in IgAN patients: renal tissue WT1 was negatively correlated with renal tissue IL-6,mesangial hyperplasia,glomerular sclerosis,renal tubular atrophy/interstitial fibrosis,blood Creatinine,urine protein in IgAN patients(r =-0.738,r =-0.610,r =-0.448,r =-0.655,r =-0.562,r =-0.468,P <0.001,P <0.001,P = 0.002,P <0.001,P<0.001,P= 0.001),and positively correlated with renal tissue Klotho,e GFR,urine osmolality,albumin(r = 0.566,r = 0.551,r = 0.389,r = 0.337,P <0.001,P < 0.001,P = 0.009,P = 0.025);(4)Correlation of urine Klotho with pathology and clinical indicators in IgAN patients: urine Klotho protein was negatively correlated with renal tubular atrophy/ interstitial fibrosis,blood creatinine,and urine protein in IgAN patients(r=-0.365,r =-0.432,r =-0.301,P = 0.015,P = 0.003,P = 0.047),and positively correlated with Klotho of renal tissue and e GFR(r=0.374、r=0.474,P=0.012、P=0.001).Conclusions:1.Klotho protein may play a protective role in the kidney by indirectly protecting IgA nephropathy podocytes and inhibiting inflammatory response to reduce renal tubule interstitial damage.2.Urine Klotho protein may indirectly reflect the impairment of renal function,providing a non-invasive detection method for the evaluation and monitoring of IgA nephropathy patients. |
