Longitudinal assessment of renal function after lung transplantation for cystic fibrosis: transition from post-operative acute kidney injury to acute kidney disease and chronic kidney failure

Vittorio Scaravilli, Alessandra Merrino, Francesca Bichi, Fabiana Madotto, Letizia Corinna Morlacchi, Mario Nosotti, Alfredo Lissoni, Lorenzo Rosso, Francesco Blasi, Antonio Pesenti, Alberto Zanella, Giuseppe Castellano, Giacomo Grasselli, Vittorio Scaravilli, Alessandra Merrino, Francesca Bichi, Fabiana Madotto, Letizia Corinna Morlacchi, Mario Nosotti, Alfredo Lissoni, Lorenzo Rosso, Francesco Blasi, Antonio Pesenti, Alberto Zanella, Giuseppe Castellano, Giacomo Grasselli

Abstract

Introduction: The clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown.

Methods: Incidence and risk factors for post-operative AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used.

Results: Eighty-three patients were included. Creatinine peaked 3[2-4] days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (p = 0.009) and CKD (p = 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (p = 0.0001), ICU stay (p = 0.0001), and hospital stay (p = 0.0001), and increased the incidence of primary graft dysfunction (p = 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34-10.2), p = 0.0131 and 2.65(1.02-6.87), p = 0.0443, respectively.

Discussion: AKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.

Keywords: Acute kidney disease; Acute kidney injury; Chronic kidney disease; Cystic fibrosis; Lung transplantation.

Conflict of interest statement

VS received funding support for publication of the present paper from Fondazione Ricerca Fibrosi Cistica. # FFC 27/2019. The remaining authors do not have any potential conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Overall incidence of renal dysfunction. AKI acute kidney injury, AKD acute kidney disease, CKD chronic kidney disease
Fig. 2
Fig. 2
Incidence of acute kidney injury and impact on long-term chronic kidney disease. A Mosaic plot of the incidence of acute kidney disease vs. acute kidney injury during ICU stay. AKI acute kidney injury, ICU intensive care unit. The width, height, and area of the rectangles are proportional to the number of patients per cohort, the frequency of acute kidney injury stage, and the cell frequencies of the contingency table. AKI acute kidney injury, AKD acute kidney disease. B Mosaic plot of the incidence of 1-year follow-up chronic kidney disease vs. acute kidney injury during ICU stay. AKI acute kidney injury, ICU intensive care unit. The width, height, and area of the rectangles are proportional to the number of patients per cohort, the frequency of acute kidney injury stage, and the cell frequencies of the contingency table. AKI acute kidney injury, CKD chronic kidney disease
Fig. 3
Fig. 3
Serum Creatinine trajectory over time. sCR serum creatinine, ICU intensive care unit, CKD chronic kidney disease. Blue and red dots represent sCr concentration of patients with CKD stage ≤ 2 and CKD stage > 2, respectively. Blue and red lines represent cubic spline interpolation (λ = 0.05) of sCr of patients with CKD stage ≤ 2 and CKD stage > 2, respectively, with associated 95% confidence intervals as the colored areas
Fig. 4
Fig. 4
Probability of survival. Left panel: Kaplan − Meier estimates of the unadjusted cumulative probability of survival following acute kidney injury (AKI). Red and blue lines represent patients with AKI stage = 3 and AKI stage 

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