Author:

Abstract:

The genetic basis of ADPKD is well known but the pathogenic role of the polycystins is poorly understood. Apart from the well-known effect of the intrinsic loss of PC-1 and PC-2 on cyst proliferation and growth, an important pathophysiological role is attributed to the immune system, both adaptive and innate. Thus, the infiltration of immune cells may be directly caused by the underlying molecular PKD defects. Recently we have reviewed the literature on an intriguing finding in ADPKD, notably the disease's association with cytopenia The strongest association was observed with alterations in the lymphocytic lineages. The question arises whether cytopenia is another and yet unrecognized extra-renal manifestation of ADPKD, directly linked to genetic factors. Sparse and conflicting data already suggested a tendency to greater vulnerability for cancer and infections in ADPKD posttransplant patients compared with transplant recipients with kidney disease of other etiologies. Whether cytopenia explains these findings is yet unknown. Apart from the finding of numerically altered cell counts in ADPKD patients, hematological cell function and alterations in other immunological parameters have not been investigated so far. Considering the above-mentioned role of the immune system in the development of the ADPKD phenotype, mapping the broad immunological profile of ADPKD patients is of interest. Recent observations highlighted the importance of cationic channels in both adaptive and innate immune cell development, maturation and activation. PC1/PC-2 could hypothetically be involved in immunological cell development, maturation and activation. We feel that further investigation of the observed association between ADPKD and cytopenia in well-defined clinical cohorts and exploring the links with clinical outcomes, could bring new insight in the physiological role of polycystins and immune cell development. Cytopenia could also be an easy to obtain biomarker for disease progression in ADPKD. Furthermore, if expression of PKD-1 and PKD-2 could be demonstrated in other hematological cells besides B-lymphoblastoid cells, it could be a first step in explaining the observed association between cytopenia and ADPKD. As such, the cytopenia observed in ADPKD patients would be a yet unrecognized extra-renal manifestation of ADPKD directly linked to the genetic basis of the disease. Further, revealing the underlying immunological profile of ADPKD patients could bring new insight in the pathogenesis of the disease and especially the important inflammatory component in its pathogenesis. It could reveal pathophysiological cascades as a target for new therapeutic agents.