HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome.
There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P < 0.02) and 5 years (36% vs. 72%, P < 0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P < 0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses.
Konrad
M
M
Division of Pediatric Nephrology, University of Heidelberg, Germany.
Mytilineos
J
J
Ruder
H
H
Opelz
G
G
Schärer
K
K
D000293:Adolescent; D017668:Age of Onset; D000477:Alkylating Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002699:Chlorambucil / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004247:DNA / Q000032:analysis; D005260:Female; D015809:HLA-DR7 Antigen / Q000097:blood*; D006801:Humans; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000188:drug therapy*; D012150:Polymorphism, Restriction Fragment Length; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use*
D000477:Alkylating Agents; D000893:Anti-Inflammatory Agents; D015809:HLA-DR7 Antigen; D013256:Steroids; D002699:Chlorambucil; D003520:Cyclophosphamide; D004247:DNA; D011241:Prednisone