Pre-transplant Mean Pulmonary Artery Pressure Independently Predicts Acute Kidney Injury After Lung Transplant

By Brian Stephany, MD

Since the first successful lung transplantation in 1963, national lung transplant volume continues to rise annually. A significant proportion of lung transplant patients develop perioperative acute kidney injury (AKI), reported in the range of 39 to 65 percent, with 5 to 10 percent needing dialysis. Data in the nontransplant population clearly demonstrate worse short- and long-term outcomes, including mortality, with even mild and self-limited AKI.

Similarly, recent evidence suggests that AKI immediately after lung transplantation is positively correlated to in-hospital and long-term mortality as AKI severity increases. Acute kidney injury also predicts a longer duration of mechanical ventilation, a longer stay in the intensive care unit and hospital, an increased cost of care, a faster rate of decline of estimated glomerular filtration rate (eGFR) and an increased risk of chronic kidney disease.

Some analyses of independent predictors of perioperative AKI in this high-risk group have documented an increased risk in patients undergoing transplantation for idiopathic pulmonary arterial hypertension (IPAH). Furthermore, AKI in patients with IPAH was more likely to be severe, requiring renal replacement therapy. However, mean pulmonary arterial pressure (mPAP) can be elevated in a multitude of pulmonary diseases that more commonly lead to lung failure requiring transplantation beyond IPAH. To that end, we sought to investigate the association between measured pre-transplant mPAP by pulmonary artery catheterization and perioperative AKI in lung transplant recipients, regardless of the underlying primary lung diagnosis.

We identified 354 lung allograft recipients transplanted between 1997 and 2009 with available preoperative pulmonary artery pressure measurements. We categorized patients as having no pulmonary hypertension (PH) (mPAP < 25 mm Hg; n = 162), mild PH (mPAP 25 to 34 mm Hg; n = 133), moderate PH (mPAP 35 to 45 mm Hg; n = 39) or severe PH (mPAP > 45 mm Hg; n = 20) prior to transplant. Acute kidney injury was defined by an absolute rise in creatinine within 48 hours of transplant by > 0.3 mg/dL, according to the Acute Kidney Injury Network classification schema.

Analysis of this dataset identified a graded incidence of perioperative AKI based on baseline measured mPAP:

• No PH (n = 60): 37 percent incidence of perioperative AKI
• Mild PH (n = 68): 51 percent incidence of perioperative AKI
• Moderate PH (n = 26): 67 percent incidence of perioperative AKI
• Severe PH (n = 17): 85 percent incidence of perioperative AKI (p<0.001 vs no PH)

For every 10-mm Hg increase in baseline mPAP, there was an associated 1.7 (95 percent CI, 1.4- 2.2) increased odds of AKI. Controlling for age, gender, race, single vs. double lung transplant, pre-transplant diabetes, baseline creatinine, etiology of lung disease, intraoperative administration of vasopressors and/or inotropes, baseline mPAP, and initial postoperative PaO2/FiO2, independent covariates that remained significantly associated with AKI post-transplant included:

• Vasopressor/inotrope use (odds ratio 2.3 [95 percent CI, 1.3-4.3])
• Baseline creatinine (odds ratio 4.9, [95 percent CI, 1.2-21.1] per 1-mg/dL increase)
• Initial PaO2/FiO2 (odds ratio 0.8 [95 percent CI, 0.7-0.9] per 50-unit increase)
• Baseline mPAP (odds ratio 1.5 [95 percent CI, 1.2-2.1] per 10-mm Hg increase)

These data confirm our suspicion that regardless of the lung diagnosis, elevated baseline mPAP independently predicts an increased risk of AKI immediately after lung transplantation in a dose-dependent manner. These data are clinically relevant when such candidates can be identified and ideally targeted for early employment of renal protective strategies such as avoidance of nephrotoxic medications, overaggressive diuresis and contrast use as well as closer hemodynamic monitoring. Future study of the underlying pathophysiologic mechanisms of susceptibility to AKI in addition to novel use of kidney biomarkers that can better characterize impaired renal reserve may lead to improved prophylactic measures that could be instituted before transplantation.

Dr. Stephany (stephab@ccf.org) is a Staff Physician in the Glickman Urologic & Kidney Institute’s Department of Nephrology and Hypertension.