Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors

Introduction: Kallistatin, a serine protease inhibitor, has been implicated in cardiovascular and renal protection. This study investigates its association with clinical characteristics and outcomes in long-term kidney transplant recipients (KTRs). Methods: In this longitudinal observatio...

Full description

Saved in:
Bibliographic Details
Main Authors: Krzysztof Batko, Anna Sączek, Małgorzata Banaszkiewicz, Jolanta Małyszko, Ewa Koc-Żórawska, Marcin Żórawski, Karolina Niezabitowska, Katarzyna Siek, Andrzej Kraśniak, Marcin Krzanowski, Katarzyna Krzanowska
Format: Article
Language:English
Published: Karger Publishers 2025-01-01
Series:Kidney & Blood Pressure Research
Online Access:https://karger.com/article/doi/10.1159/000543652
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850133681092427776
author Krzysztof Batko
Anna Sączek
Małgorzata Banaszkiewicz
Jolanta Małyszko
Ewa Koc-Żórawska
Marcin Żórawski
Karolina Niezabitowska
Katarzyna Siek
Andrzej Kraśniak
Marcin Krzanowski
Katarzyna Krzanowska
author_facet Krzysztof Batko
Anna Sączek
Małgorzata Banaszkiewicz
Jolanta Małyszko
Ewa Koc-Żórawska
Marcin Żórawski
Karolina Niezabitowska
Katarzyna Siek
Andrzej Kraśniak
Marcin Krzanowski
Katarzyna Krzanowska
author_sort Krzysztof Batko
collection DOAJ
description Introduction: Kallistatin, a serine protease inhibitor, has been implicated in cardiovascular and renal protection. This study investigates its association with clinical characteristics and outcomes in long-term kidney transplant recipients (KTRs). Methods: In this longitudinal observational cohort study, we enrolled 101 KTRs between September 2016 and October 2017. The median (interquartile range) time post-transplant was 52 (36–97) months, and the follow-up time was 83 (41–85) months. All patients had documented graft function of ≥24 months and no record of acute rejection or active or chronic infection at presentation. Serum kallistatin and high-sensitivity interleukin-6 were measured at baseline using commercially available enzyme-linked immunosorbent assays. A control group of 32 healthy volunteers was also recruited. Results: Higher serum kallistatin levels were observed in KTRs compared to healthy controls (15.9 vs. 13.8 µg/mL; p = 0.007). Concentrations were lower in diabetic versus non-diabetic KTR (14.8 vs. 16.4 µg/mL; p = 0.021). A significant interaction between diabetic status and body mass index indicated a positive association with kallistatin levels only in diabetic KTRs (p = 0.046). Linear mixed models assessing estimated glomerular filtration rate (eGFR) change over time showed improved fit after kallistatin was included in a base model with age, sex, and baseline eGFR (p = 0.024). Cox regression showed that higher kallistatin levels were associated with an increased risk of graft loss (HR: 1.120; p = 0.049), but also remained independent of time after transplantation (HR: 1.147; p = 0.030). No association was observed for all-cause mortality. The best performance was estimated for kallistatin models adjusting for time post-transplant (c-index 0.779) and diabetic status (c-index 0.707). Conclusion: This study highlights the complex interactions between kallistatin, renal function, and cardiometabolic status in stable, long-term KTRs. Higher kallistatin levels are associated with an increased risk of graft loss in non-diabetic patients while showing a protective effect in diabetic patients. These findings support integrated management of cardio-reno-metabolic health in KTRs.
format Article
id doaj-art-5c74c7ca8d704ac3adc2f03a40c84ebe
institution OA Journals
issn 1423-0143
language English
publishDate 2025-01-01
publisher Karger Publishers
record_format Article
series Kidney & Blood Pressure Research
spelling doaj-art-5c74c7ca8d704ac3adc2f03a40c84ebe2025-08-20T02:31:55ZengKarger PublishersKidney & Blood Pressure Research1423-01432025-01-0150122123110.1159/000543652Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant SurvivorsKrzysztof BatkoAnna SączekMałgorzata BanaszkiewiczJolanta MałyszkoEwa Koc-ŻórawskaMarcin ŻórawskiKarolina NiezabitowskaKatarzyna SiekAndrzej KraśniakMarcin KrzanowskiKatarzyna Krzanowska Introduction: Kallistatin, a serine protease inhibitor, has been implicated in cardiovascular and renal protection. This study investigates its association with clinical characteristics and outcomes in long-term kidney transplant recipients (KTRs). Methods: In this longitudinal observational cohort study, we enrolled 101 KTRs between September 2016 and October 2017. The median (interquartile range) time post-transplant was 52 (36–97) months, and the follow-up time was 83 (41–85) months. All patients had documented graft function of ≥24 months and no record of acute rejection or active or chronic infection at presentation. Serum kallistatin and high-sensitivity interleukin-6 were measured at baseline using commercially available enzyme-linked immunosorbent assays. A control group of 32 healthy volunteers was also recruited. Results: Higher serum kallistatin levels were observed in KTRs compared to healthy controls (15.9 vs. 13.8 µg/mL; p = 0.007). Concentrations were lower in diabetic versus non-diabetic KTR (14.8 vs. 16.4 µg/mL; p = 0.021). A significant interaction between diabetic status and body mass index indicated a positive association with kallistatin levels only in diabetic KTRs (p = 0.046). Linear mixed models assessing estimated glomerular filtration rate (eGFR) change over time showed improved fit after kallistatin was included in a base model with age, sex, and baseline eGFR (p = 0.024). Cox regression showed that higher kallistatin levels were associated with an increased risk of graft loss (HR: 1.120; p = 0.049), but also remained independent of time after transplantation (HR: 1.147; p = 0.030). No association was observed for all-cause mortality. The best performance was estimated for kallistatin models adjusting for time post-transplant (c-index 0.779) and diabetic status (c-index 0.707). Conclusion: This study highlights the complex interactions between kallistatin, renal function, and cardiometabolic status in stable, long-term KTRs. Higher kallistatin levels are associated with an increased risk of graft loss in non-diabetic patients while showing a protective effect in diabetic patients. These findings support integrated management of cardio-reno-metabolic health in KTRs. https://karger.com/article/doi/10.1159/000543652
spellingShingle Krzysztof Batko
Anna Sączek
Małgorzata Banaszkiewicz
Jolanta Małyszko
Ewa Koc-Żórawska
Marcin Żórawski
Karolina Niezabitowska
Katarzyna Siek
Andrzej Kraśniak
Marcin Krzanowski
Katarzyna Krzanowska
Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
Kidney & Blood Pressure Research
title Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
title_full Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
title_fullStr Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
title_full_unstemmed Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
title_short Unravelling the Role of Serum Kallistatin on Cardiorenal Outcomes in Kidney Transplant Survivors
title_sort unravelling the role of serum kallistatin on cardiorenal outcomes in kidney transplant survivors
url https://karger.com/article/doi/10.1159/000543652
work_keys_str_mv AT krzysztofbatko unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT annasaczek unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT małgorzatabanaszkiewicz unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT jolantamałyszko unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT ewakoczorawska unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT marcinzorawski unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT karolinaniezabitowska unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT katarzynasiek unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT andrzejkrasniak unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT marcinkrzanowski unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors
AT katarzynakrzanowska unravellingtheroleofserumkallistatinoncardiorenaloutcomesinkidneytransplantsurvivors