Decreased intraplatelet Ca2+ release and ATP secretion in pediatric nephrotic syndrome.

Platelets play an important role in the natural history of idiopathic nephrotic syndrome (NS). Although thromboembolic events are rare, the activation of circulating platelets is generally considered an important factor in the prethrombotic state in children with NS. Platelet-activating factor (PAF), a potent endogenous phospholipid mediator of inflammation, stimulates intracellular free calcium (Ca2+) mobilization, aggregation, and release reactions in platelets obtained from normal donors. Platelet-related effects of PAF in children with NS are unknown. We studied PAF-induced intracellular Ca2+ mobilization in washed platelets and ATP secretion in platelet-rich plasma in 34 children with idiopathic NS and in 7 healthy children. There was a significant decrease in ATP secretion: 0.021+/-0.011 microg/10(7) cells with 20 nM PAF and 0.089+/-0.017 microg/10(7) platelets with 200 nM PAF versus control values (0.195+/-0.004 microg/10(7) and 0.813+/-0.09 microg/10(7), respectively). Moreover, PAF-evoked increase in intracellular free Ca2+ concentration was twofold lower in NS patients than in control subjects (230.1+/-22.4 nM versus 455.6+/-15.3 nM). Also, thrombin-induced intracellular free Ca2+ mobilization was diminished in children with NS compared with the control group. Thus, contrary to expectations, a decrease of platelet reactivity in response to PAF in vitro was observed in children with idiopathic NS. We suggest that this decreased platelet reactivity may reflect a period refractory to PAF and may be considered as platelet desensitization to PAF released in vivo in children with NS.

[Plasmapheresis in the combined therapy of progressive forms of glomerulonephritis]. / Plazmaferez v kompleksnoi terapii progressiruiushchikh form glomerulonefrita.

29 patients aged 6-16 with glomerulonephritis lasting 4-5 years received multimodality treatment with plasmapheresis as a component. The majority of the patients suffered from primary glomerulonephritis in mesangio- or membrano-proliferative morphological variants. Previous long-term conventional therapy (prednisolone, cytostatics, anticoagulants and antiaggregation drugs) failed. The test course comprised 1-3 plasmapheresis sessions (centrifuge method on [symbol: see text] apparatus), cyclophosphamide or maintenance methyl-prednisolone pulse therapy, heparin and curantil. One-third of the patients achieved remission lasting from 5 months to 3 years, in the other one-third the improvement was as short as 2-4 weeks, and the last one-third appeared non-responders. Improvement of clinical indices occurred in parallel with trends to reduction in the levels of CIC, IgG, B-lymphocytes, T-helpers, inhibition of lymphocyte succinate dehydrogenase activity, better phagocytosis. No complications which may prohibit plasmapheresis use in glomerulonephritis were observed. Adjuvant plasmapheresis use in glomerulonephritis treatment needs further studies.

[The first experience of using membranotropic agents in the treatment of the nephrotic syndrome]. / Pervyi opyt ispol'zovaniia membranotropnykh sredstv v lechenii nefroticheskogo sindroma.

To treat children suffering from the nephrotic syndrome, use was made of the membrano-stabilizing agents: zaditen that also has an antiallergic action; dimephosphon, a membrano-stabilizer and immunomodulator. The basis for differentiated use of the drugs was formed by the examination data which enabled one to identify the signs of atopy in children with the hormone-dependent nephrotic syndrome, marked signs of the instability of cellular membranes and different immunologic deviations in children with the hormone-resistant variety of the nephrotic syndrome. During zaditen treatment, the majority of the children with the hormone-resistant nephrotic syndrome manifested an appreciable decrease of the process activity; in some cases, including those with hormone dependence, the treatment with prednisolone could be reduced. In part of the children with the hormone-resistant nephrotic syndrome, the treatment with dimephosphone resulted in a decrease of proteinuria, reduced the instability of cellular membranes, and improved the immunologic parameters.