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The treatment of minimal change nephrotic syndrome (lipoid nephrosis): cooperative studies of the Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN).

Minimal change nephrotic syndrome (MCNS) is the most frequent type of nephrotic syndrome (NS) in childhood. During the last decade only little progress has been made in the understanding of the etiology and pathogenesis of MCNS. However, treatment has been improved pragmatically by controlled cooperative studies, which have lead to an unexpected degree of standardization in pediatric nephrology. The Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN) is conducting its own cooperative studies in close contact with the International Study of Kidney Diseases in Children (ISKDC). In Steroid Study II of APN two regimens of initial prednisone treatment are compared: standard initial versus short initial prednisone therapy. Preliminary results reveal that a complete remission of NS can be obtained with less than half of the prednisone dose usually applied by the standard regimen. The relapse rate after initial treatment, however, seems to be the same in both groups. In the Cytotoxic Drug Study I of APN the effectiveness of chlorambucil (0.15 mg/kg for 8 weeks) or cyclophosphamide (2 mg/kg for 8 weeks) in the treatment of steroid toxic frequent relapsers without steroid dependency (FRNS) and with steroid dependency (SDNS) are compared. In FRNS the treatment is followed by long lasting remissions in most cases, while in SDNS relapses occur very soon again. The latter group, therefore, does not profit from cytotoxic drugs in the dosage used. In a new trial, therefore, it is asked whether patients with SDNS will profit more from prolongation of cyclophosphamide treatment for 12 weeks.

Child↗
PubMed2002

Cytokine mRNA profile in lipoid nephrosis: evidence for increased IL-8 mRNA stability.

BACKGROUND/AIMS: Proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) is presumed to be due to the effect of circulating factors on glomerular permeability to plasma proteins. This study examines the expression of messenger ribonucleic acid (mRNA) for cytokines thought to mediate glomerular inflammation during different stages of the nephrotic syndrome. METHODS: Messenger RNA expression and stability from peripheral blood mononuclear cells of IMLNS patients in relapse and in remission, and age matched normal controls were measured using a ribonuclease protection assay (RPA). The spontaneous and Interleukin 2 (IL-2) stimulated mRNA expression were studied. RESULTS: Spontaneous mRNA expression for Interleukin 8 (IL-8) from IMLNS patients in relapse was significantly increased when compared to IMLNS patients in remission and normal controls (p < 0.05). After 14 h of IL-2 stimulation, mRNA IL-8 levels expressed by IMLNS PBMC patients in remission were not different from those observed in normal controls. However, after 5 days of PBMC incubation, a significant increase in mRNA for IL-8 in IMLNS patients compared to controls was found (p < 0.01). Stability assay demonstrated that IL-8 mRNA transcript from the nephrotic patients remained higher than those from controls and showed a significantly prolonged life t(1/2) (p = 0.02). CONCLUSIONS: IL-8 mRNA expression is increased in IMLNS patients in relapse. Moreover, stability studies show that IL-8 mRNA life t(1/2) is prolonged due to altered post-transcriptional regulation. This finding may explain the elevated serum IL-8 levels observed in these patients during relapse and may have pathogenic significance since IL-8 has been shown to induce proteinuria in the experimental animal.

Adolescent↗