Chronic Kidney Disease and Acute Kidney Injury Outcomes Post Left Ventricular Assist Device Implant

Abstract


Methods
This is a retrospective study of all patients who received continuous-flow LVAD at our institution from January 2015 until August 2017. We calculated the incidence of AKI and the need for RRT post-LVAD implant, as well as the rate of renal recovery and survival rates at 30 days and 1-year post-LVAD implant. The presence of chronic kidney disease (CKD) and proteinuria was assessed, and kidney ultrasound results were reviewed on all patients, if available. CKD was present if estimated glomerular filtration rate (eGFR) was <60 mL/min per 1.73m 2 for ≥3 months preceding LVAD implant and/or presence of proteinuria ≥ 20 mg/dL on two or more urine samples prior to LVAD implant and/or an abnormal kidney ultrasound with increased echogenicity, small size <9 cm or scarring. AKI was defined as per the current Kidney Disease Initiative Global Outcomes (KDIGO) guidelines.

Results
A total of 137 patients received LVAD during this time period. There were 112 males and 25 females with a mean age of 59.2 years. Incidence of AKI and the need for RRT post-LVAD implant were 64% and 19.7%, respectively. Sub-group analysis was performed based on the presence of CKD, advanced CKD stage (Stage 1-2 vs 3-5), proteinuria and abnormal kidney ultrasound. The incidence of AKI post-LVAD implant was significantly higher if baseline CKD was present (P = 0.028), and patient had an advanced CKD stage (P = 0.008). The need for RRT post-LVAD implant was significantly higher if baseline CKD was present (P = 0.015), and the patient had an abnormal kidney ultrasound (P = 0.04). Thirty-day and one-year mortality rates post-LVAD implants were 4.3% and 21.1%, respectively for the entire cohort. Out of the 27 patients requiring RRT, nine (33.3%) came off RRT before one year. Compared to the eGFR on the day of LVAD implant, eGFR at 30 days post-LVAD implant was higher in 57% and lower in 42% patients. At one year, this eGFR improvement reversed and eGFR was lower in 67% and higher in 32% patients.

Introduction
Heart failure remains a leading cause of morbidity and mortality worldwide with an estimated 6.5 million adults in the United States presenting with heart failure [1]. It was a contributing cause of one in eight deaths in 2017 and costs the nation an estimated $30.7 billion in 2012 [1][2]. In general, the mortality following hospitalization for patients with heart failure is 10.4% at 30 days, 22% at one year, and 42.3% at five years, despite marked improvement in medical and device therapy [3]. Drug therapy has been the cornerstone of mild-moderate heart failure with some success in severe heart failure cases [4]. Nevertheless, the survival and the quality of life of patients with severe heart failure remain limited. Other options for severe NYHA class 3-4 heart failure include cardiac transplantation which provides substantial individual benefit, but with approximately 3,500 heart transplants performed each year worldwide, more than half of which are in the US, the overall impact on disease burden is still small [5].
Left ventricular assist devices (LVAD) are an electromechanical device for assisting cardiac circulation, which is used either to partially or to completely replace the function of a failing heart. The first LVAD system was created by Domingo Liotta at Baylor College of Medicine in Houston in 1962. The first successful implantation of an LVAD was completed in 1966 by Dr. Michael E. DeBakey to a 37-year-old woman. A Para corporeal (external) circuit was able to provide mechanical support for 10 days after the surgery [6]. Since the inception of the artificial heart program at the National Institutes of Health (NIH) in 1964, various circulatory-support devices have been developed for short-term use in patients with end-stage heart failure [7]. In 1994, the Food and Drug Administration (FDA) approved pneumatically driven LVADs as a bridge to transplantation, and self-contained, vented electric devices were approved for this purpose in 1998 [8]. Since then, the ventricular assist device technology has evolved significantly from a larger pulsatile flow device (Heartmate 1) designed for temporary use to a more compact continuous flow device (Heartmate 2 and 3) that gained acceptance as a bridge to transplantation or destination therapy for patients with end stage heart failure [9][10][11]. Shortterm use of these devices in patients awaiting transplantation normalizes hemodynamics, improves end-organ dysfunction and exercise tolerance, allows patients to be sent home, and provides a reasonable quality of life, with a relatively low incidence of major adverse events [12][13][14].
The kidneys receive approximately 25% of the cardiac output (about 1.0 to 1.1 liters per minute) and depend on the cardiac output to maintain enough glomerular perfusion and thus the glomerular filtration rate (GFR) [15]. Heart and kidney are closely related, and heart failure often precipitates acute kidney injury (AKI) with further worsening of volume overload and pulmonary congestion leading to the cardio-renal syndrome. The presence of underlying chronic kidney disease or a decreased renal reserve increases the risk of acute kidney injury in the setting of heart failure. LVADs are implanted to provide circulatory support by assisting the cardiac pump function. This should theoretically improve renal perfusion although possible renal hypoperfusion during the perioperative period remains a risk for developing AKI. The effects of LVAD implant on renal function including the rate of post-operative AKI and longterm effects on renal function have been reported by various centers performing LVAD placement. But most studies did not report underlying chronic kidney disease and patient's baseline GFR in steady-state three months or more prior to the LVAD implant. As most patients have fluctuating kidney function at or around the time of LVAD implant due to severe heart failure, an assessment of their baseline renal function is not possible unless old records are available from period when the patient was not acutely sick.
We present a retrospective study from a single center reporting the association of underlying CKD and renal outcomes post-LVAD implant. We aim to identify baseline renal risk factors that can help stratify potential LVAD candidates.

Materials And Methods
We present a retrospective study reporting the incidence of AKI and the need for renal replacement therapy (RRT) in patients who received an LVAD at our institution from January 2015 to August 2017. A baseline CKD status of all patients was obtained if data available and post-LVAD implant renal outcomes were reported in correlation with the baseline CKD status. All patients received continuous-flow LVAD implant for indications of Class 3 or 4 NYHA heart failure due to ischemic or non-ischemic cardiomyopathy.
Data was obtained from chart review after appropriate IRB approval. We calculated the incidence of AKI and the need for RRT post-LVAD implant and reviewed charts for up to oneyear post-LVAD implant to monitor renal outcomes. We identified renal risk factors and reviewed data prior to LVAD implant to obtain baseline kidney function of each patient. We included the presence of CKD, advanced CKD stage (Stage 3 or higher), proteinuria, and an abnormal kidney ultrasound as the renal risk factors and studied their impact on the incidence of AKI and RRT need post-LVAD implant. CKD was defined as a structural or functional abnormality of the kidney lasting ≥3 months. Proteinuria was defined as the presence of >20 mg/dL protein on urine analysis on at least 2 samples obtained prior to the LVAD implant. Abnormal kidney ultrasound (KU) included abnormal echogenicity, small kidneys <9 cm, scarring or presence of multiple complex kidney cysts. AKI was defined per current KDIGO guidelines and further categorized as Stage 1, 2, or 3 AKI [16]. Stage 1 AKI includes an increase in serum creatinine (Cr) 1.5-1.9 times from baseline or increase in serum Cr of ≥0.3 in 48 h. Stage 2 AKI includes an increase in serum Cr 2.0-2.9 times from baseline, and stage 3 AKI includes serum Cr increase ≥3 times from baseline or need for RRT.
Data was kept secure and de-identified. Statistical analysis of the data was done using Chisquare test. A P-value of ≤0.05 was considered statistically significant.

Results
A total of 137 patients received LVAD implant during the specified time period. There were 112 male and 25 female patients with a mean age of 59.2 years. Racial distribution included 63 Caucasians, 38 African Americans, 29 Hispanics, and five Asians. Patients were divided into two main groups based on the presence or absence of underlying CKD, and sub-group analysis was done separately for renal risk factors including advanced CKD stage (stage 3 or higher), proteinuria, and presence of an abnormal kidney ultrasound. The baseline characteristics of the patients, including in our study, are reported in Table 1.  Patients in the CKD group were slightly older than the non-CKD patients. Male to female ratio was comparable. CKD group had higher burden of comorbidities including hypertension, diabetes mellitus and history of coronary artery bypass surgery. They had slightly lower mean hemoglobin and platelet counts. CKD group patients had a poor INTERMACS profile which represents a sicker state. INTERMACS profile provides a general description of the patients receiving LVAD or heart transplantation [17]. INTERMACS 2 profile represent a steady decline state with a patient who has been demonstrated "dependent" on inotropic support but nonetheless shows signs of continuing deterioration in nutrition, renal function, fluid retention, or other major status indicator. INTERMACS profile 3 describe a stable but inotrope dependent state after repeated documentation of failure to wean without symptomatic hypotension, worsening symptoms, or progressive organ dysfunction.

CKD group No CKD group
Overall incidence of AKI in LVAD recipients was 64.3% including all stages. RRT (either continuous veno-venous hemodialysis or conventional hemodialysis) was required in 19.7% patients post-LVAD implant. Sub-group analysis was performed based on the presence of underlying renal risk factors to see if incidence of AkI or need for RRT post-LVAD implant differ significantly ( Table 2).  Baseline CKD status was available for 126 patients. Out of those, 84 patients had CKD present and 42 patients had no underlying CKD. In the CKD present group (N = 84), a total of 64 patients had AKI post-LVAD implant and 23 patients required RRT. The incidence of AKI and the need for RRT were 76 % and 27%, respectively. In the no underlying CKD group (N = 42), a total of 18 patients developed AKI and four needed RRT. Thus, incidence of AKI was 43% and need for RRT was 9%. The difference between the incidence of AKI post-LVAD implant in CKD and no CKD groups was statistically significant (P = 0.028). Similarly, the difference between the incidence of RRT need post-LVAD implant in CKD and no CKD groups was also statistically significant (P = 0.0153).

Incidence of AKI P-value Incidence of RRT P-value
We further divided patients based on the baseline CKD stage. Patients with underlying CKD 1 and 2 stage (N = 25) had incidence of AKI 60% (N = 15) and RRT needed in 6 (24%) patients. Patients with CKD 3 (N = 42) had incidence of AKI 88% (N = 37) and RRT needed in 8 (19%) patients. Patient with CKD 4 (N = 5) had an incidence of AKI 80% (N = 4) and RRT was needed in 4 (80%) patients. There was only one patient with underlying CKD 5/ESRD who was on maintenance dialysis prior to admission and he required RRT. 11 patients had CKD based on the presence of proteinuria or an abnormal kidney ultrasound but did not have eGFR results available from ≥ 3 months prior to LVAD implant and thus were excluded from the CKD staging sub-group analysis. Compared to CKD 1-2, a higher CKD stage 3-5 was a statistically significant risk factor for AKI post LVAD implant (P = 0.008). However, compared to CKD 1-2, a higher CKD stage 3-5 was not a statistically significant risk factor for RRT need post-LVAD implant (P = 0.78).
Proteinuria was present in 45 (33%) patients and absent in 85 (62%) patients. 7 (5%) patients had no prior proteinuria assessment available. In the patient with no proteinuria, AKI post-LVAD implant occurred in 49 (58%) patients and 15 (17.6%) patients required RRT. 1 patient was initiated on RRT prior to LVAD implant. In the patient with proteinuria, AKI post-LVAD implant occurred in 33 (73%) patients and 10 (22.2%) patients required RRT. The presence of proteinuria was not a statistically significant risk factor for AKI post-LVAD implant (P=0.078). Similarly, the presence of proteinuria was not a statistically significant risk factor for RRT need post-LVAD implant (P = 0.5288).
Kidney ultrasound results were reviewed for all patients. 103 patients had normal kidney ultrasounds and 24 had abnormal results. 10 patients did not get a kidney ultrasound prior to LVAD implant. In patients with normal kidney ultrasound, 63 (61%) patients had AKI post-LVAD implant and 16 (15.5%) patients required RRT. 1 patient was initiated on RRT prior to LVAD implant. In patients with an abnormal kidney Ultrasound, 17 (71%) patients suffered AKI, and eight (33%) patients required RRT. The presence of an abnormal kidney ultrasound was not a statistically significant risk factor for AKI post-LVAD implant (P = 0.376), but the presence of an abnormal kidney ultrasound was a statistically significant risk factor for RRT need post-LVAD implant (P = 0.0448).

Mortality and Dialysis Independence Post-LVAD Implant
All LVAD recipients were followed for up to 1-year post implant and 30 day and 1-year mortality rates post-LVAD implant were calculated. For those patients who required RRT post LVAD-implant, the rate of dialysis freedom/renal recovery was calculated at 1-year post implant. (Table 3). Mortality rate at 30 days and 1-year post LVAD implant was 4.3% and 21.1% respectively for the entire cohort. The mortality rate was higher if underlying CKD was present and this difference was statistically significant at 1-year post-LVAD implant (P = 0.0001; Table  3; Figure 1).