Efficacy And Safety Evaluation Of Tacrolimus Combined With Glucocorticoid For Primary IgA Nephropathy In Children

Objective: This study retrospectively analyzed the efficacy and safety of Tacrolimus(TAC)combined with glucocorticoid(hereinafter referred to as hormone)in the treatment of primary Ig A nephropathy(Ig AN)in children,so as to seek a better treatment method for Ig AN children.Methods: Retrospective analysis was performed on 28 children with primary Ig AN diagnosed by renal biopsy who were admitted to the Renal Immunology Department of Hebei Children’s Hospital from September 2012 to May 2020.For children with nephrotic syndrome or nephrotic level proteinuria(24-hour urinary protein quantitative >50mg/kg)or with renal pathology showing moderate or above mesangial hyperplasia but less than25% glomerular involvement with crescent-forming,direct administration of TAC(0.05-0.1mg/kg/d)combined with the prednisone(1.5-2.0 mg/kg/d)(maximum dose was given50 mg or less)oral;According to the severity of the disease,for children with crescent nephritis or with crescent formation involving more than 25% of glomerulus in renal pathology,a large dose of sodium methylprednyl Succinate(15-20 mg /kg/d)(the maximum dose ≤1g)was given three times every other day.The patients were then given TAC(0.05-0.1mg/kg/d)combined with prednisone(1.5-2.0mg/kg/d)(Max≤50mg)orally.Collected before and after treatment in children with 1,3,6,12 months routine urine,24 h urine protein quantitative,routine blood,serum albumin,blood fat,liver function,renal function,correcting the endogenous creatinine clearance,fasting glucose,TAC blood drug concentration data,and records the TAC possible adverse reactions(e.g.,blood glucose,liver and kidney function is damaged,neurotoxicity,etc.).Results: A total of 28 children with primary Ig AN were included in this study,and the complete/partial response rate of these 28 children was evaluated.After 12 months of TAC combined with hormone treatment,the complete response rate was 67.8%(19/28),the partial response rate was21.4%(6/28),and the overall response rate was 89.2%(25/28).The effectiveness and safety of 25 children without midway drug change or other immunosuppressant were evaluated.Before treatment with TAC,the urine protein level of 25 children was(3.65±1.56)g/24 h,serum albumin level of(31.15±8.19)g/L,cholesterol level of(6.63±2.45)mmol/L.By the end of follow-up(12 months after treatment observation),the urine protein level had decreased to(0.19±0.06)g/24 h.Serum albumin increased to(44.93±3.18)g/L and cholesterol decreased to(3.91±0.78)mmol/L.The urine protein level was significantly lower than that before treatment,and the difference of urine protein concentration at different time points was statistically significant(F=10.551,P=0.001).Serum albumin increased to normal levels.Fasting blood glucose fluctuated within the normal range before and after treatment,but the difference of fasting blood glucose at different time points was statistically significant(P<0.05).There were no significant changes in serum creatinine and liver function before and after treatment(P>0.05).Aderse reactions occurred in the follow-up included 2 cases of uncontrollable hand tremor,3 cases of elevated serum creatinine,corrected endogenous creatinine clearance rate <90ml/(min·1.73 ㎡),1 case of frequent abdominal pain,diarrhea and other gastrointestinal reactions,and 3 cases of slightly increased fasting blood glucose,which returned to normal only after adjusting diet.During the follow-up,there were no adverse events such as bone marrow suppression,severe infection,recurrent respiratory tract infection and impaired liver function.Conclusion: TAC combined with hormone is effective in the treatment of primary Ig AN in children,with rapid onset and high safety.The total effective rate is 89.2% after 3 months of treatment,and there is no obvious toxic and side effects during the medication observation period,which is worthy of promotion and use in clinical treatment.