**7. Conclusions**

in order to avoid the severe consequences of rapid and irreversible loss of renal function or from severe pulmonary hemorrhage. Both can be avoided by appropriate initial immunosup‐ pressive treatment [60]. In pulmonary-renal syndrome better understanding of interorgancrosstalk is of utmost importance, as current clinical care is many times limited to preventive

In main clinical entities (Goodpasture´s disease, ANCA associated vasculitis, SLE-associated vasculitis) induction and maintenance immunosupression is achieved by steroids and cyclophosphamide. Intensive plasma exchange to remove pathological antibodies, proinflammatory cytokines, complement compounds and factors of coagulation from circulation is beneficial for patients with pulmonary hemorrhage and severe kidney disease. Except of antibody removal, plasma exchange may have also other immunoregulatory effects and could potentiate the effects of immunosuppressive drugs [61]. Exchange procedures have beneficial effect on long-term renal recovery [62, 63]. Severe renal function impairment requires haemodialysis and progression to end stage renal failure renal replacement therapy is required [17]. In case of inevitable ICU admission supportive care is important as well.

During immunosuppressive regimes nosocomial infection used to be a common complication associated with high mortality [64]. Therefore minimizing the risk of infection has the highest of high priority. Patients with pulmonary-renal syndrome are often hypotensive because of a combination of dehydration, haemorrhage and systemic inflammatory response and may therefore require inotropic support [28]. Endotracheal intubation, tracheostomy, lung

Antioxidant effect of N-acetylcystein published by Fernández-Fernández and Sesma [65] in one patient with WG and also our unpublished experience suggests clinical improvement of systemic inflammation. Administration of NAC is based on two significant studies: the IFIGENIA trial in 2005 [66] (Idiopathic Pulmonary Fibrosis International Group Exploring Nacetylcysteine I Annual study) and the study by Guilpain et al. [42]. Both studies have reported that NAC significantly reduced the activation of MPO and improved the survival of endothelial cells. In a recent experimental study by Lee et al. [67] continuous infusion of NAC attenuated inflammatory response and acute lung and kidney injury after hemorrhagic shock

Some recent studies are focused on anti-TNF molecules, anti-B-cells blockers [68], anti-BlyS [69], anti-IL5 molecules [70], antithymocyte globulin [71], blockers of costimulatory molecules [72], tyrosine-kinase inhibitors [73] and proteasome inhibitors [74]. The results of these studies are sometimes controversial but there is a real hope that they will provide useful knowledge

Many questions still remain unanswered also in the use of intravenous immunoglobulins (IVIG). Such treatment should be considered as an effective regimen in many "off label" indications particularly in cases where standard immunosuppressive regimes fail or could be harmful. Despite some evidence of efficacy, dosage and timing of IVIG therapy, as well as the question of its costs/benefit ratio still remain insufficiently documented and controlled trials

protective ventilation, transfusion and anticoagulation may be also necessary.

in rats. This result supports the clinical experience.

with definitive conclusions for clinical indications are needed.

in the near future.

and supportive measures [24].

84 Updates in the Diagnosis and Treatment of Vasculitis

Pulmonary-renal syndrome is a complex and heterogenous clinical picture involving rapid progressive glomerulonephritis and pulmonary capillaritis based on inflammation and necrosis of vessel wall. Morphological changes of pulmonary-renal syndrome are consequences of immunologically mediated processes and the unconctrolled derangement of the immune system could cause multiorgan dysfunction and fatal outcome.

The diagnostic procedure should focus on recognizing the earliest phases of the initiation and progression of the inflammation through a reliable panel of immunological and organ specific functional markers. In the near future novel diagnostic tools should be introduced in the diagnosis and differential diagnosis of pulmonary-renal syndrome, including gene expression profiles, cytokine profiles, markers of oxidative stress and many others.

Traditional clinical approach to treat pulmonary-renal syndrome was divided among rheumatologists, nephrologist and pneumologists but the improving knowledge of its pathogenesis clearly indicates the need of an interdisciplinary team work incorporating intensive care specialists and immunologists as well. This integrative approach could pave the way toward the introduction of more efficient novel treatment regimes. Another challenge is the high risk of relapses in these condition occurring up to 50 %, of the patients. Early establishment of the exact diagnosis and effective etiology oriented treatment in such cases is rather difficult task requiring further experimental and clinical research and cooperation of different specialists.

[3] Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG et al.Nomenclature of systemic vasculitides.Proposal

Immunological Mechanisms and Clinical Aspects in Pulmonary-Renal Syndrome: A Review

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Perspective therapeutic approaches based on contemporary immunological knowledge (B-cell depletion, costimulatory molecule blockers, siRNAs controlling intracellular processes, cytokine treatment) supported by clinical experience will bring benefits for induction and maintenance of remission or also excluding the menacing catastrophic scenario of the disease.
