| Background and ObjectiveIgA nephropathy(IgAN)is the most common primary glomerulonephritis in China and around the world.Its 10-year renal survival rate is low,and some patients can rapidly progress to end-stage renal disease,which brings a heavy burden to patients families and countries.Studies on the pathogenesis and progress of IgAN are particularly important.In recent years,a large number of clinical studies have found that serum uric acid plays an important role in the development of IgAN,and the incidence of hyperuricemia in IgAN is much higher than that of other nephropathy and normal population.Some scholars have proposed that hyperuricemia is an independent risk factor for IgAN development.However,other studies have suggested that hyperuricemia does not have prognostic value for all IgAN patients,and has different clinical guiding value for different gender and different conditions of chronic kidney disease(CKD)stage.The stability of serum uric acid is regulated by renal function,uric acid production and various uric acid transporters on renal tubular cells.However,there are a variety of differentially expressed genes in IgAN.Whether these genes affect the regulation of uric acid and contribute to the high incidence of hyperuricemia is unclear.This study aims to through the analysis of the large sample long-term followup study from 1000 cases of patients with IgAN disease progress,to study the effect of high uric acid hematic disease in them,and through the extracted from peripheral blood B cell IgAN patients mRNA,application of the depth of the genome sequencing technology,screening of two kinds of common disease onset may potentially susceptibility genes,provide new targets for treatment of high uric acid hematic disease and IgAN.Methods1.Collect on January 1,2010 to December 31,2019,tianjin medical university general hospital kidney internal medicine by renal biopsy diagnosis of primary,1022 cases of hospitalized patients with IgAN,further into the to our regular follow-up and complete data of a total of 463 cases of patients,analysis of patients admitted to hospital blood uric acid level and clinical and pathological indicators,the relationship between the numerical average blood uric acid during follow-up,patients with analysis of the average level of uric acid and IgAN patients progress and prognosis of renal function.2.Selection on June 1,2019 to June 31,2019,tianjin medical university general hospital kidney internal medicine by renal biopsy in hospitalized patients diagnosed with primary IgAN 18 patients and the healthy volunteers in 5 cases,the separation of peripheral blood B lymphocytes and extract the RNA genome sequencing depth,screening the difference of IgAN genes,and merges according to whether the patients with high uric acid hematic disease,the sifting high uric acid hematic disease related genes.Another 20 inpatients with newly diagnosed IgAN,including 10 with hyperuricemia and 10 without hyperuricemia,were selected to isolate peripheral blood B lymphocytes and extract RNA.Real-time PCR was used to verify the expression of the differential genes.Results1.This study found that the incidence of hyperuricemia in 1022 cases of IgAN was 36.69%,and the higher the CKD stage,the higher the incidence(P < 0.01).High uric acid hematic disease group and the high uric acid hematic disease,quantitative proportion of male,serum creatinine,urine protein,and glomerular sclerosis,renal tubular atrophy and interstitial fibrosis crescents formation significantly higher(P < 0.05),while the glomerular filtration rate decreased significantly(P < 0.05),renal tubular atrophy/interstitial fibrosis and serum creatinine level is high uric acid hematic disease group of independent risk factors(T1: OR = 1.835,95% CI = 1.257 2.678,P = 0.002;T2: OR=1.994,95%ci =1.221-3.256,P=0.006;SCr: OR=1.015,95%ci =1.010-1.020,P < 0.001).Follow-up,found in 463 cases of patients with IgAN and progress compared with renal progression-free group,group of male ratio,average creatinine,uric acid values,and glomerular sclerosis,renal tubular atrophy/interstitial fibrosis significantly increased(P < 0.05),hemoglobin decreased significantly(P < 0.05),the average level of uric acid are independent risk factors renal progression of IgAN patients(OR = 1.009,95% CI = 1.004 1.013,P < 0.001).Patients whose average uric acid was higher than the normal range during follow-up had faster renal function progression and worse prognosis(P < 0.05),and had a higher risk of renal function progression(OR=2.928,95%ci: 1.475-5.810,P=0.006).Subgroup analysis showed that elevated mean serum uric acid level was an independent risk factor for disease progression in female patients,but not in male patients(female: HR=1.012,95%ci =1.006-1.019,P < 0.001;male: HR=1.005,95%ci =0.997-1.012,P=0.21).2.In this study,a total of 155,443 genes were deeply sequenced,and 11,538 differentially expressed genes(P < 0.05)and 3901 differentially expressed genes(P < 0.01)were found in IgAN patients and healthy people.A total of 420 differentially expressed genes were found(P < 0.01).The correlation analysis between differentially expressed genes and serum uric acid indicated that a total of 68 differentially expressed genes were significantly different(P < 0.001).Real-time PCR showed that the expression of three susceptible genes SAC3D1,THOC2 and TTC12 in IgAN combined with hyperuricemia was significantly different(P < 0.05).Conclusion1.The prevalence of hyperuricemia is increased in IgAN patients,and renal tubular atrophy/interstitial fibrosis is more severe in patients with hyperuricemia.Elevated mean serum uric acid levels are independent risk factors for IgAN progression,especially in women.2.Abnormal expression of susceptibility genes TTC12,SAC3D1 and THOC2 may be involved in the co-occurrence of IgAN and hyperuricemia,providing a new target for the treatment of IgAN and hyperuricemia. |
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