MO020AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE, CYTOPENIA AND POSTTRANSPLANT OUTCOMES: A RETROSPECTIVE ANALYSIS
Authors: Schellekens Pieter , Mekahli Djalila , Vennekens Rudi , Meyts Isabelle , Kuypers Dirk , Bammens Bert 
Published: May 2021

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenetic inherited kidney disease, has been reported to be associated with distinct cytopenias. The pathophysiological mechanism behind this association and its clinical implications are unknown. Sparse and conflicting data have suggested a tendency to greater vulnerability for cancer and infections in ADPKD renal transplant recipients as compared to their non-ADPKD counterparts. Furthermore polycystin expression has been demonstrated in lymphocytes in vitro with impact on lymphocyte function. From this background, cytopenia could be hypothesized to be directly induced by the molecular PKD defects and to impact on outcome in affected patients. The main interest of the current study is to confirm the association between ADPKD and cytopenia in a well-defined clinical cohort of patients at the time of kidney transplantation. Furthermore, the impact of ADPKD and cytopenia on posttransplant outcomes is studied.

Method
Baseline (pre-transplantation) and follow-up data from all patients who underwent a first renal transplantation between 01/04/1964 and 01/09/2019 at the Leuven University Hospitals were retrieved from the renal transplantation database.

Results
4103 patients were included: 611 ADPKD and 3492 non-ADPKD. Immediately before transplantation, significant differences in total white blood cell (6.33 +/- 2.59 ADPKD versus 7.17 +/- 2.21 non-ADPKD; p&lt;0.0001), neutrophil (4.04 +/- 1.59 versus 4.54 +/- 1.88; p&lt;0.0001), lymphocyte (1.45 +/- 0.05 versus 1.57 +/- 0.68; p&lt;0.0001), basophil (0.041 +/- 0.084 versus 0.046 +/- 0.048; p&lt;0.0001), eosinophil (0.23 +/- 0.24 versus 0.29 +/- 0.33; p&lt;0.0001) and thrombocyte counts (203.00 +/- 67.21 versus 230.18 +/- 76.00; p&lt;0.0001) between ADPKD and non-ADPKD patients were observed. After multiple linear regression analysis, ADPKD remained significantly associated with total white blood cell, neutrophil, monocyte and thrombocyte counts.
In terms of post-transplant outcomes, significant univariate differences between ADPKD and non-ADPKD transplant recipients in favor of the ADPKD patients were observed for overall survival, time to first rejection and time to transplant failure. On the contrary, a significantly faster onset of the first posttransplant malignancy and infection was observed in ADPKD as compared to non-ADPKD. Furthermore, the numbers of posttransplant infections and malignancies tended to be higher in the ADPKD patient cohort, the number of transplant rejections was significantly lower. While pre-transplantation lymphopenia was univariately associated with lower overall survival, none of the other post-transplant outcomes was associated with lymphopenia, nor with any of the other blood cell counts. After multivariate Cox proportional hazard regression analysis, ADPKD remained significantly associated with time to first rejection (p=0.0310; HR 0.632) and overall survival (p&lt;0.0001; HR 0.512). None of the blood cell count variables retained significance in the multivariate outcome models.

Conclusion
This large retrospective single center study confirmed the association between cytopenia and ADPKD immediately before kidney transplantation. Furthermore, ADPKD was also associated with differences in posttransplant outcomes. In multivariate survival analysis, the impact of ADPKD on outcomes outweighed that of other variables, amongst others the blood cell counts. From this, it is tempting to speculate that ADPKD influences outcome through a disease-related impact on blood cells, however many more factors are most probably involved. The hypothesis that cytopenia could be an extra-renal manifestation of ADPKD, directly linked to its genetic basis, and its impact on outcome warrant further investigation.