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

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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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.

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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 (2021). https://doi.org/10.1007/s00467-021-04937-9

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Keywords

  • ADPKD
  • Leukopenia
  • Lymphopenia
  • Ciliopathies
  • CKD