| Study 1 Prospective study of Tacrolimus induction treatmentin diffuse proliferative lupus nephritisObjective: To investigate the clinical efficacy and side effects of tacrolimus(FK506) in the induction treatment of patients with diffuse proliferative lupus nephritis(DPLN) and factors that may influence the clinical efficacy of FK506.Methodology:A prospective study was conducted in 20 patients with urinary protein excretion >1.5g/24h, active urine sediment, normal renal function and DPLN(WHO class Ⅳ) proven by renal biopsy. The patients were subdivided into group A [patients who received pulse intravenous methylprednisolone(MP)] , group B(patients who did not receive pulse intravenous MP) ,group C (patients who were newly diagnosed), group D (patients who were relapsed), group E (patients whose SLEDAI are more than 15 prior to FK506 treatment)and group F(patients whose SLEDAI are between 10 and 15). All the patients received the protocol of FK506 combined with steroids. The initial dose of FK506 was 0.08-0. 1mg/kg · d, together with prednisone (Pred ) 0.6mg/kg · d. 7 patients also received pulse intravenous MP prior to oral Pred. The dose of Pred was tapered after 4 weeks until a maintenance dose of 10mg /d. Clinical efficacy was defined as complete remission ,partial remission and no-response. Complete remission(CR) was defined as urinary protein excretion < 0.4g/24h, no active urine sediment, serum albumin >35g/L, normal renal function and anti-dsDNA antibody negative. No response referred to reduction of proteinuria < 50% of baseline , persistent active urine sediment, serum albumin ≤ 30g/L.Partial remission (PR )wasdefined as stable renal function with reduction of proteinuria by > 50% of baseline or proteinuria within the range of 0.4- 2.0g/24h, serum albumin ^30g/L. Results :The duration of FK506 treatment in 20 patients was 10.3 ±6.23 (6~ 27)months. SLEDAI decreased from 13.8 ±3.29 to 3.68 ±3.28 (P <0.01). 85%(25%CR, 60%PR)and 95%(50% CR, 45%PR) patients achieved remission after 3 and 6 months'treatment. The time to reach PR and CR was 2.18± 1.33(1-6) and 4.50±2.84 (l-lO)months respectively .More patients achieved CR in groupA,C,E than in group B,D and F respectively and time to CR in group A, C and E was shorter than those in Group B , D and F respectively. The average whole blood trough concentration of FK506 within six months' treatment in patients with CR was higher than those with PR and NR(7. 13±3. 16 vs 5. 40±2. 90 vs 5. 5'ng/ml). Repeated renal biopsy in 16 patients ( 7 with CR ,9 with PR) demonstrated that the cellular crescents, fibrinoid necrosis/ karyorrhexis, microthrombi were markedly improved, the glomerular immune deposits also reduced significantly, the activity index decreased from 10.6 ±4.10 to 4.50±2.99(p < 0.01). There was no obvious exacerbation of interstitial fibrosis. No patient withdrew because of drug side effects. The SCr increased temporarily more than 25% of the baseline value in 5 patients (25%)within the first month treatment, the blood concentration of FK506 in 4 of them was higher and CYP3A5 genotype was *3/*3 and SCr recoverd to normal range after adjustment of the dosage. Other adverse effects included transient elevated liver enzyme, hyperglycemia ,herpes zoster, etc. 9 patients discontinued FK506 treatment after achieving remission. After 18-46 months of follow-up, 1 patient relapsed and theothers were on sustained remission.Conclusions: The results demonstrated that tacrolimus combined with cortisteroids could control the activity of DPLN effectively and rapidly. This regimen was safe. Factors that may influence the clinical efficacy of the FK506 included the steroid dose, therapeutic history ,the disease activity and the average whole blood trough concentration of FK506.Study 2 Prospective study of tacrolimus combined with steroids in patients with membranous lupus nephropathyObjective: To investigate the efficacy and adverse effects of tacrolimus combined with steroids in patients with membranous lupus nephropathy. Methodology: 19 patients with membranous lupus nephritis (WHO 1982 Classification V) proved by renal biopsy were enrolled in this prospective clinical trial. The patients were subdivided into Group A ( 5 in Va and 5 in Vb)and Group B( 3 in Vc and 6 in Vb).The excretion of urinary protein in all the patients was more than 2.0g/24h,and the serum creatinine(SCr) was less than 1.5mg/dl. All the patients received a regimen of FK506 combined with steroids. The starting dose of FK506 was O.lmg/kg *d, in accompany with prednisone(pred) 0.6mg/kg *d. The dose of pred was tapered after 4weeks until a maintenance dose of lOmg /d. Clinical efficacy was defined as complete remission ,partial remission and no-response. Complete remission(CR) referred to urinary protein less than 0.4g/24h, no active urine sediment, serum albumin >35g/L,renal function normal and anti-dsDNA antibody negative. No response(NR) referred to the group showing decrease of urinary protein less than 50% of the baseline value, or increase of SCr more than 50% of the baseline value. Partial remission (PR )referred to urinary protein 0.4-2.0g/24h, and the reduction of unirary protein was more than 50% of the baseline value, serum albumin =^30g/L. Results: 1 patient withdraw because of treatment -related side effect, the other 18 patients received FK506 treatment for 6-42months. At 3 months posttreatment,...
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