Secondary resistance to cyclosporin A in children with nephrotic syndrome.
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.
Sairam
Vellore K
VK
Department of Pediatrics, Division of Pediatric Nephrology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0373, USA.
Kalia
Alok
A
Rajaraman
Srinivasan
S
Travis
Luther B
LB
D000477:Alkylating Agents / Q000627:therapeutic use; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use
D000477:Alkylating Agents; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine