Clonal haematopoiesis of indeterminate potential and impaired kidney function—A Danish general population study with 11 years follow-up

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The myeloproliferative neoplasms are associated with chronic kidney disease but whether clonal haematopoiesis of indeterminate potential (CHIP) is associated with impaired kidney function is unknown. In the Danish General Suburban Population Study (N = 19 958) from 2010 to 2013, 645 individuals were positive for JAK2V617F (N = 613) or CALR (N = 32) mutations. Mutation-positive individuals without haematological malignancy were defined as having CHIP (N = 629). We used multiple and inverse probability weighted (IPW)-adjusted linear regression analysis to estimate adjusted mean (95% confidence interval) differences in estimated glomerular filtration rate (eGFR; ml/min/1.73 m2) by mutation status, variant allele frequency (VAF%), blood cell counts, and neutrophil-to-lymphocyte ratio (NLR). We performed 11-year longitudinal follow-up of eGFR in all individuals. Compared to CHIP-negative individuals, the mean differences in eGFR were −5.6 (−10.3, −0.8, p =.02) for CALR, −11.9 (−21.4, −2.4, p = 0.01) for CALR type 2, and −10.1 (−18.1, −2.2, p =.01) for CALR with VAF ≥ 1%. The IPW-adjusted linear regression analyses showed similar results. NLR was negatively associated with eGFR. Individuals with CALR type 2 had a worse 11-year longitudinal follow-up on eGFR compared to CHIP-negative individuals (p =.004). In conclusion, individuals with CALR mutations, especially CALR type 2, had impaired kidney function compared to CHIP-negative individuals as measured by a lower eGFR at baseline and during 11-year follow-up.

OriginalsprogEngelsk
BogserieEuropean Journal of Haematology
Vol/bind109
Udgave nummer5
Sider (fra-til)576-585
Antal sider10
ISSN0902-4441
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The authors would like to convey our gratefulness to all staff and participants in the General Suburban Population Study. In addition, the authors would like to convey our gratitude to Medical and Research Secretary Mette Grymer Jensen for her important logistical and organisational role. This work was supported by grants from: the Region Zealand Research Foundation, Manufacturer Einar Willumsens Memorial Foundation, Anders Hasselbalch's Foundation Fighting Leukemia, Carpenter Joergen Holm and Wife Elisa F. Hansen's Memorial Foundation, Else and Mogens Wedell‐Wedellborgs Foundation, the Hoejmosegaard Scholarship, Eva and Henry Fraenkels Memorial Foundation, Dagmar Marshalls Foundation, Candys Foundation, A.V. Lykfeldt and Wife's Scholarship, and Aase and Ejnar Danielsen's Foundation. GESUS was funded by the Region Zealand Research Foundation, Naestved Hospital Foundation, Naestved Municipality, Johan and Lise Boserup Foundation, TrygFonden, Johannes Fog's Foundation, Region Zealand, Naestved Hospital, The National Board of Health, The Local Government Denmark Foundation. Thomas Stiehl obtained The Lundbeck Foundation Fellowship: Personalized prediction of blood cancer progression using clinical data and mathematical modeling (R335‐2019‐2020) under which Morten K. Larsen is funded.

Funding Information:
Steffen Koschmieder discloses research funding from Novartis, Bristol‐Myers Squibb, Janssen/Geron, and AOP Pharma; advisory board honoraria from Pfizer, Incyte, Ariad, Novartis, AOP Pharma, BMS, Celgene, Geron, Janssen, CTI, Roche, Bayer, Sanofi and Abbvie; patent für BET inhibitor at RWTH Aachen University; honoraria from Novartis, BMS, Celgene, Geron, Janssen, Pfizer, Incyte, Ariad, Shire, Roche, AOP Pharma, Abbvie; and other financial support (e.g., travel support) from Alexion, Novartis, BMS, Incyte, Ariad, AOP Pharma, Baxalta, CTI, Pfizer, Sanofi, Celgene, Shire, Janssen, Geron, Abbvie, Karthos. Yunus Çolak discloses personal fees from AstraZeneca, Boehring‐Ingelheim and Sanofi Genzyme outside the submitted work. Hans C. Hasselbalch discloses research funding from Novartis and AOP Orphan. Other authors declare no conflict of interest.

Publisher Copyright:
© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

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