| BackgroundFocal segmental glomerulosclerosis is a common cause of primary nephrotic syndrome in adults and a common glomerular disease leading to end-stage renal disease,which is clinically characterized by massive proteinuria,nephrotic syndrome,sometimes hypertension and renal insufficiency.Proteinuria is an important factor in promoting the progression of renal function,reducing proteinuria can effectively delay the progression of renal function and improve long-term prognosis of the disease.Guidelines and consensus in China and abroad recommended that glucocorticoids therapy be considered only in idiopathic FSGS associated with clinical features of the nephrotic syndrome,supportive management including ACEI/ARB are suggested for patients with non-nephrotic syndrome.However,the disease shows an extensive heterogeneity in clinical and pathology,i t is always difficult to achieve the satisfactied therapeutic effect with glucocorticoids alone,the incidence of steroid resistance and steroid dependence is high,which is not beneficial for the treatment of the disease,but also brings a variety of side effects related to glucocorticoids.In addition,relevant research and clinical observations in China and abroad pointed out that urine protein exceeding 1000mg/24 h is an independent risk factor for deterioration in renal function and supportive treatment is poor in effect,leading to chronic progression of the disease.In recent years,with the appearance and application of a variety of new immunosuppressive agents,the treatment of FSGS has made great progress.Tacrolimus,a calcineurin inhibitor,is used for the treatment of FSGS due to its strong immunosuppressive and non-immunosuppressive effects.Multiple studies reported good effect of TAC in decreasing proteinuria and protecting renal function.Simultaneously,the use of TAC draw lessons from foreign guidelines and transplant rejection,the dose is large and the blood concentration is high,therefore,side effects such as sepsis,impaired glucose tolerance and nephrotoxicity are common,and most side effects can be alleviated after reduction or withdrawal,it is concluded that the occurrence of side effects are related to the high dose and high concentration of TAC.For patients with FSGS,the effective and safe dose and concentration of TAC is the focus of scholars.This study retrospectively analyz ed the clinical efficacy and safety of low concentration TAC combined with glucocorticoids in the initial treatment of idiopathic FSGS,hoping to provide a basis for the population to explore a better treatment options.Objective1.To compare the effects of low concentration of TAC combined with glucocorticoids and glucocorticoids alone in reducing proteinuria and improving renal function in idiopathic FSGS,and provide more evidence for the clinical effectiveness of TAC.2.To assess the clinical safety of low concentration TAC combined with glucocorticoids therapy.Methods41 patients with idiopathic FSGS diagnosed by clinical manifestation and renal biopsy in the Department of Nephrology,Southwest Hospital from November 2011 to October 2016,with urinary protein excretion exceeding 1000 mg/24 h were included in this retrospective study.According to the therapeutic regimen,41 patients were divided into a low concentration TAC group1 and a hormone group1.Further,28 patients with urinary protein excretion exceeding 2 000 mg/24 h were divided into TAC group2 and a hormone group2 on the basis of the above method.Therapy regimen: TAC group received initial dose of oral TAC of 0.02-0.05 mg /(kg·d),divided into two dose,detected 12 hours of blood concentration after 7 days of treatment,and then adjust the dose and frequency,gradually titrated to the concentration of 3-5 ng/mL,an initial dose of oral prednisone 0.5-1 mg /(kg·d)(maximum dose does not exceed 80 mg/d)were given at the same time;The hormone group was given dose of oral prednisone 1 mg/(kg·d)(maximum dose not exceed 80 mg/d);the dose of prednisone in two groups was reduced after 8 weeks,and the dose was reduced by 5 mg every 4 weeks to 15 mg and maintain the dose.All patients received ACEI or ARB therapy,calcium channel blocker is given when blood pressure >135/85 mmHg.urinary protein excretion,estimated glomerular filtration rate and remission rate before treatment and 1,3,6,12,18,24 months after treatment were collected and ana lysed.Meanwhile,the adverse effects were also recorded.Results1.Comparison of the effectiveness of the two groupsIn patients whose urinary protein excretion were greater than 1 000 mg/24 h,24-hour urinary protein excretion was decreased significantly 1 month later in the TAC group,it began to decrease evidently 3 months later in hormone group(P<0.05).The reduction of 24-hour urinary protein excretion were more obvious in the TAC group at 18 and 24 months after treatment than the hormone group(P<0.05).In patients whose urinary protein excretion was much than 2 000 mg/24 h,24-hour urinary protein excretion was decreased significantly after 1,3,6,12,18,24 months treatment in the TAC group(P<0.05).However,the indicator declined obviously at 1,3,6 months after treatment(P<0.05),no significant differences were seen at 12,18,24 months compared with values of baseline in the hormone group(P>0.05).Recurrence rate were lower significantly in the TAC group than the hormone group in both cases(P<0.05).There was no significant difference in the total effective rate and complete remission rate between TAC group and the hormone group(P>0.05).2.Comparison of the safety of the two groupsThere were 3 cases of respiratory infection,1 case of herpes zoster,1 case of impaired glucose tolerance,2 cases of abnormal liver function in the TAC group;2 cases of respiratory infection,1 case of urinary tract infection,2 cases of abnormal liver function,and 2 cases of reduced bone mass.3 cases of steroid-induced diabetes in the hormone group.The incidence of adverse reactions in the TAC group and hormone group was 29.2% and 58.8% respectively.There was no statistical difference in adverse effect between the two groups(P>0.05).Conclusions1.In the treatment of idiopathic FSGS,low dose [0.02-0.05 mg /(kg·d)] ? low concentration(3-5ng/mL)TAC combined with glucocorticoid took effect quickly,steadily,and was more effective in reduction of urinary protein excretion than the only use of hormones,the therapeutic scheme was a better option for this population.2.Compared with the regimen of single hormonal,increased adverse reactions were not found in the regimen of low concentration tacrolimus combined with hormone,the new treatment regimen showed a good clinical safety. |
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