Calcineurin inhibitors treatment in kidney transplant recipients is frequently associated with hyperkalemia, acidosis and hypertension but not with increased expression or phosphorylation of the sodium chloride cotransporter
Abstract
Background and hypothesis Calcineurin inhibitors (CNIs), widely used after kidney transplantation, may alter signaling pathways regulating the NaCl cotransporter (NCC), potentially causing an acquired form of pseudo-hypoaldosteronism type II (PHAII), characterized by hyperkalemia, metabolic acidosis, and hypertension. Methods We assessed the prevalence of a PHAII-like phenotype in kidney transplant recipients (KTRs) receiving CNIs in two independent cohorts: a retrospective cohort (n = 172) and a prospective cohort (n = 58). In the prospective cohort, NCC and phosphorylated NCC (pNCC) abundance were measured in urinary extracellular vesicles (uEVs). Results Approximately 25% of KTRs exhibited a PHAII-like phenotype in both cohorts. Contrary to expectations, NCC and pNCC expression in uEVs were lower in CNI-treated KTRs than in healthy volunteers. No differences in NCC or pNCC abundance were observed between KTRs with and without the phenotype. Similarly, kidney transplant biopsies from patients with the phenotype showed NCC and pNCC staining comparable to control biopsies from patients with minimal change disease. Conclusion Although hyperkalemia, metabolic acidosis, and hypertension frequently coexist in CNI-treated KTRs, the absence of NCC upregulation does not support the hypothesis that chronic CNI therapy induces the characteristic molecular abnormalities of PHAII.
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BibTeX
@article{ascia2026calcineurin,
title = {{Calcineurin inhibitors treatment in kidney transplant recipients is frequently associated with hyperkalemia, acidosis and hypertension but not with increased expression or phosphorylation of the sodium chloride cotransporter}},
author = {Ludovic Di Ascia and Jennifer Baraka-Vidot and Cyril Ferdynus and Jean-Paul Duong and Céline Bairras Martin and Pierre Merville and Lionel Couzi and Dominique Eladari and Régine Chambrey},
journal = {Frontiers in Nephrology},
year = {2026},
month = oct,
doi = {10.3389/fneph.2026.1917605},
url = {https://u-picardie.hal.science/hal-05839079v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Calcineurin inhibitors treatment in kidney transplant recipients is frequently associated with hyperkalemia, acidosis and hypertension but not with increased expression or phosphorylation of the sodium chloride cotransporter
AU - Ludovic Di Ascia
AU - Jennifer Baraka-Vidot
AU - Cyril Ferdynus
AU - Jean-Paul Duong
AU - Céline Bairras Martin
AU - Pierre Merville
AU - Lionel Couzi
AU - Dominique Eladari
AU - Régine Chambrey
PY - 2026
DA - 2026/10/22
JO - Frontiers in Nephrology
DO - 10.3389/fneph.2026.1917605
UR - https://u-picardie.hal.science/hal-05839079v1
AB - Background and hypothesis Calcineurin inhibitors (CNIs), widely used after kidney transplantation, may alter signaling pathways regulating the NaCl cotransporter (NCC), potentially causing an acquired form of pseudo-hypoaldosteronism type II (PHAII), characterized by hyperkalemia, metabolic acidosis, and hypertension. Methods We assessed the prevalence of a PHAII-like phenotype in kidney transplant recipients (KTRs) receiving CNIs in two independent cohorts: a retrospective cohort (n = 172) and a prospective cohort (n = 58). In the prospective cohort, NCC and phosphorylated NCC (pNCC) abundance were measured in urinary extracellular vesicles (uEVs). Results Approximately 25% of KTRs exhibited a PHAII-like phenotype in both cohorts. Contrary to expectations, NCC and pNCC expression in uEVs were lower in CNI-treated KTRs than in healthy volunteers. No differences in NCC or pNCC abundance were observed between KTRs with and without the phenotype. Similarly, kidney transplant biopsies from patients with the phenotype showed NCC and pNCC staining comparable to control biopsies from patients with minimal change disease. Conclusion Although hyperkalemia, metabolic acidosis, and hypertension frequently coexist in CNI-treated KTRs, the absence of NCC upregulation does not support the hypothesis that chronic CNI therapy induces the characteristic molecular abnormalities of PHAII.
SN - 2813-0626
ER -