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Cytopenia in autosomal dominant polycystic kidney disease (ADPKD): merely an association or a disease-related feature with prognostic implications?

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is associated with distinct cytopenias in observational studies; the most consistent and strongest association is seen with alternations in the lymphocytic lineages. Although the underlying mechanism of these associations is unclear, it has been hypothesized to be secondary to sequestration of white blood cells in cystic organs, or related to the uremic environment in chronic kidney disease (CKD). However, since mutations in PKD1 or -2 affect several immunomodulating pathways, cytopenia may well be an unrecognized extrarenal manifestation of ADPKD. Furthermore, many important questions on the clinical implications of this finding and the effect on the disease course in these patients are unanswered. In this review article, we provide an overview of the current evidence on cytopenia in ADPKD and explore the underlying mechanisms of this association and its potential prognostic implications. Based on the current literature, we hypothesize that polycystin deficiency can disturb immune cell homeostasis and that cytopenia is thus an intrinsic feature of ADPKD, related to genetic factors. Taken together, these findings warrant further investigation to establish the exact etiology and role of cytopenia in patients with ADPKD.

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Abbreviations

ADPKD:

autosomal dominant polycystic kidney disease

PC-1:

polycystin 1

PC-2:

polycystin 2

ER:

endoplasmic reticulum

CKD:

chronic kidney disease

CKD 5:

stage 5 chronic kidney disease

TRP:

transient receptor potential

IP3R:

inositol triphosphate receptor

RyR:

ryanodine receptor

SOCE:

store-operated Ca2+ entry

AC6:

adenylyl cyclase 6

PDEs:

phosphodiesterases

cAMP:

cyclic adenosine monophosphate

MIF:

macrophage inhibitory factor (MIF)

MCP-1:

monocyte chemoattractant protein-1 (MCP-1)

EPO:

erythropoietin

HSC:

hematopoietic stem cells

WBC:

white blood cell

ESA:

erythropoietin stimulating agents

HIF-2 α:

hypoxia inducible factor-2 alfa

STIM1/2:

stromal interaction molecule 1/2

CRAC:

Ca2+ release-activated Ca2+ channel (CRAC)

JAK/STAT:

Janus kinase/signal transducers and activators of transcription

JNKs:

c-Jun amino terminal kinases

Bcl-2:

B cell lymphoma 2 protein

WASp:

Wiskott–Aldrich protein

PCD:

primary ciliary dyskinesia

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Author information

Author notes

  1. Pieter Schellekens, Willem Roosens, Bert Bammens and Djalila Mekahli contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium

    Pieter Schellekens & Bert Bammens

  2. Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals of Leuven, Leuven, Belgium

    Pieter Schellekens & Bert Bammens

  3. Department of Development and Regeneration, GPURE, PKD Research Group, Laboratory of Pediatrics, KU Leuven, Leuven, Belgium

    Willem Roosens & Djalila Mekahli

  4. Department of Microbiology, Immunology and Transplantation, Inborn errors of immunity, KU Leuven, Leuven, Belgium

    Isabelle Meyts

  5. Department of Pediatrics, Pediatric Immunology, University Hospitals of Leuven, Leuven, Belgium

    Isabelle Meyts

  6. Department of Cellular and Molecular Medicine, VIB Centre for Brain and Disease Research, Laboratory of Ion Channel Research, KU Leuven, Leuven, Belgium

    Rudi Vennekens

  7. Department of Pediatric Nephrology, University Hospitals of Leuven, Leuven, Belgium

    Djalila Mekahli

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  1. Pieter Schellekens
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Contributions

DM conceived the idea for a literature review on this topic. All authors contributed to the literature search and the selection of papers for the review. PS and WR drafted the article. DM, BB, RV, and IM critically revised the article. All authors provided final approval of the version to be published.

Corresponding author

Correspondence to Pieter Schellekens.

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Schellekens, P., Roosens, W., Meyts, I. et al. Cytopenia in autosomal dominant polycystic kidney disease (ADPKD): merely an association or a disease-related feature with prognostic implications?. Pediatr Nephrol 36, 3505–3514 (2021). https://doi.org/10.1007/s00467-021-04937-9

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