Sairam Vellore K, Kalia Alok, Rajaraman Srinivasan, Travis Luther B
Department of Pediatrics, Division of Pediatric Nephrology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0373, USA.
Pediatr Nephrol. 2002 Oct;17(10):842-6. doi: 10.1007/s00467-002-0896-0. Epub 2002 Sep 14.
We investigated the phenomenon of secondary resistance to cyclosporin (CsA) in children with steroid dependent (SD) or steroid resistant (SR) nephrotic syndrome. Secondary resistance was defined as an initial response to CsA with relapse on withdrawal of therapy and absent or diminished response on reinstitution of the drug. Thirty-two children with nephrotic syndrome who were treated with CsA were included in the study. Twenty-two of the children (15 of 15 SD and 7 of 17 SR) responded while ten demonstrated primary CsA resistance. Of these 22 responders, 20 relapsed when therapy was tapered or discontinued. Cyclosporin was reinstituted in 19. Ten responded, demonstrating CsA dependence, and nine exhibited secondary CsA resistance. Focal segmental glomerular sclerosis (FSGS) was present in one patient with CsA dependence on the initial biopsy and in two of six on a subsequent biopsy. In comparison, seven of nine patients with secondary CsA resistance and ten of ten with primary CsA resistance had FSGS on the initial or subsequent biopsy ( P=0.03). C4 and/or C1q were present on the initial biopsy in one patient with CsA dependence as compared to six of nine with secondary CsA resistance ( P=0.02). Four patients with secondary CsA resistance had an accelerated progression to end-stage renal disease (ESRD). We conclude that the presence of FSGS, or of C4 and/or C1q, appears to increase the risk of secondary CsA resistance and some of these children rapidly progress to ESRD.
我们研究了激素依赖型（SD）或激素抵抗型（SR）肾病综合征患儿对环孢素（CsA）产生继发性耐药的现象。继发性耐药定义为最初对CsA有反应，但在停药后复发，且重新用药时反应缺失或减弱。本研究纳入了32例接受CsA治疗的肾病综合征患儿。其中22例患儿（15例SD患儿中的15例和17例SR患儿中的7例）有反应，10例表现为原发性CsA耐药。在这22例有反应的患儿中，20例在治疗逐渐减量或停药时复发。19例重新使用环孢素。10例有反应，表现为对CsA依赖，9例表现为继发性CsA耐药。1例CsA依赖患儿在初次活检时存在局灶节段性肾小球硬化（FSGS），6例中的2例在随后的活检中存在该病变。相比之下，9例继发性CsA耐药患儿中的7例以及10例原发性CsA耐药患儿中的10例在初次或随后的活检中存在FSGS（P = 0.03）。1例CsA依赖患儿在初次活检时存在C4和/或C1q，而9例继发性CsA耐药患儿中有6例存在（P = 0.02）。4例继发性CsA耐药患儿进展为终末期肾病（ESRD）的速度加快。我们得出结论，FSGS或C4和/或C1q的存在似乎会增加继发性CsA耐药的风险，并且这些患儿中的一些会迅速进展为ESRD。
