| Background and Objectives:IgA nephropathy(IgAN)accounts for 30%-40% of primary glomerulonephritis in China.About 10~20% of Ig AN patients would develop to end-stage kidney disease(ERSD)[1,2] in 10~20 years.Proteinuria>1g/24 h,hypertension and severe glomerular injury are important factors indicating the poor prognosis of this disease.Proteinuria level is most closely related to the progression of IgAN.Studies at home and abroad have indicated that the excretion of urine protein of IgAN patients can improve its prognosis[3,4].Compared with IgAN patients characterized by low proteinuria,single RAS blocker therapeutic regimen is often hard to achieve satisfactory result among Ig A N(1~3.5g/24h)patients with severe pathological changes(Lee ?~?).There has been no a consensus on the treatment of such patients at present.In recent years,many researches have begun to try to use glucocorticoid and immunosuppressant to treat Ig AN patients with severe illness and have achieved a good result.However,it has also been found that if immun osuppressant is selected and used improperly,it would be hard to achieve a satisfactory result and even increase side effects[5].With the advancements in researches on the applications of various new immunosuppressants in recent years,great progress has been made in term of IgAN treatment.As a macrolide drug,tacrolimus(TAC)has a mechanism of action similar to that of cyclosporine: By binding to FK506 protein in cells to reduce the activity of calcineurin,it affects the activation of T cells and the expressions of multiple cytokines[6].Since this drug has been used in the treatment of nephropathy,it has shown good curative efficacy and safety.Studies have revealed that TAC can effectively reduce the urine protein level and slow down the progression of nephropathy.However,since this drug has been used in the treatment of nephropathy only for a short term and there are a few evidence of evidence-based medicine,most of clinicians still refer to the medication scheme for its application in transplantation immunotherapy,so the initial dose is generally large and the blood concentration is maintained at a high level,characterized by side e ffects such as abnormal renal function,bone marrow suppression,infection,hyperglycemia,etc.How Ig AN patients use TAC and hormone in a safe,effective,standard and economical manner remains to be an important problem in this field.In this study,we retrospectively analyzed the efficacy and safety of TAC and glucocorticoid in a small-to-medium dose in treating Ig AN and sought a better treatment method of these patients.Methods:64 patients diagnosed of Lee ?~?nephropathy and characterized by moderate amount of urine protein at our hospital from January 2010 to January 2015 were selected retrospectively.According to the therapeutic regimen,these patients were divided into TAC + hormone group(n=34)and single hormone group(n=30).The therapeutic regimen of TAC + hormone group was as follows: TAC was orally taken with the initial dose of 0.02 ~0.05mg/(kg.d),the blood concentration at 12 h was checked 7 to 10 days after medication,and the dose and frequency were adjusted gradually to maintain the blood drug minimum concentration at 3~5ng/ml,while the initial oral dose of prednisone was 0.5mg/(kg.d)(the maximum dose was no more than 40mg/d)and was gradually reduced to 15mg/d.The therapeutic regimen of hormone group was as follows: the initial oral do se of prednisone was 1mg/(kg.d)(the maximum dose was no more than 70mg/d)and then was gradually reduced to 15mg/d.All patients were given conventional dose of ACEI or ARB.The 24-hour urine protein,liver and renal functions and blood routine tests and other data of these patients before,and 1 month,3 months and 6 months after treatment were collected and analyzed,and adverse reactions were recoded.Various clinical indicators were compared by T-test,and remission rates between different groups were examined by X~2 test.Results:The 24-hour urine protein quantifications 6 months after treatment of both patients were significantly decreased,the blood albumin levels of both groups were remarkably increased,and these indicators of each group showed significant differences compared with those before treatment(P<0.05).TAC + hormone showed a stronger role in reducing the urine protein secretion of patients,and compared with the single hormone group,the decrease of 24-hour urine protein 1 month,3 months and 6 months after treatment showed significant differences(P<0.05);but the two groups showed no statistically significant difference in complete remission rate and total effective rate(P < 0.05).During the monitoring of serum creatinine,estimated glomerular filtration rate(eGFR),no renal damage was caused by low blood concentration of TAC and small-to-medium dose of hormone,and there were no definite severe infection events during follow-up.Other adverse reactions mainly included mild blood glucose elevation,mild renal function damage,gastrointestinal reaction,headache,etc.,and there were no statistically significant differences between the two groups in terms of these adverse reactions(P>0.05).Conclusion: Low blood concentration of TAC and hormone is effective in treating Ig AN patients characterized by medium amount of urine protein.It does not increase complete remission rate compared with the single use of hormone,but this combination therapy can reduce urine protein level more effectively without increasing side effects. |
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