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Adult Circulatory Support

Risk of Renal Dysfunction Following Heart Transplantation in Patients Bridged with a Left Ventricular Assist Device

Tibrewala, Anjan*; Khush, Kiran K.; Cherikh, Wida S.; Foutz, Julia; Stehlik, Josef§; Rich, Jonathan D.*

Author Information
doi: 10.1097/MAT.0000000000001558

Abstract

Advanced heart failure (HF) is associated with substantial morbidity and mortality, with patients having an estimated mortality greater than 50% at 1 year.1,2 Heart transplantation (HT) is an established treatment for advanced HF, with over 5,000 procedures performed worldwide annually.3–5

Acute renal failure (ARF) and chronic kidney disease (CKD) occur frequently following HT and are associated with substantial morbidity and mortality. Current estimates suggest up to 25% of HT patients develop ARF and about 11% have CKD at 5 years post-transplant.6–8 About 6% of HT patients require permanent dialysis.7,8 Furthermore, patients with acute or chronic renal dysfunction are at significantly increased risk of post-transplant mortality compared with HT patients without renal impairment.6,7,9–11 Thus, ARF and CKD pose a significant burden for HT patients, and are notably associated with lower survival.

Durable left ventricular assist devices (LVAD) are often implanted as a bridge to HT. However, LVAD patients that are bridged to HT are different than non-LVAD patients in several ways including comorbidities, surgical factors, and hemodynamic characteristics.12–16 These differences affect renal function in LVAD patients.17,18

Prior studies have identified significant risk factors for ARF and CKD in patients following HT, including preoperative renal function, comorbidities, markers of underlying cardiac dysfunction, operative factors including ischemic time, and medications.7,8,10,19–21 However, these studies have not focused on patients with durable LVAD support at time of HT. In addition, the likelihood and risk factors for developing ARF and CKD following HT may be markedly different in LVAD patients compared to non-LVAD patients, and has not been previously studied.

In this study, we sought to determine the incidence of ARF requiring hemodialysis (HD) and CKD following HT in patients bridged with a durable LVAD compared with those transplanted without prior LVAD support. Further, we sought to identify risk factors for ARF requiring HD and CKD following HT specifically in patients bridged with LVAD.

Methods

Study Population

We utilized the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry.22 We identified adult patients (age ≥ 18 years old) with and without a durable, continuous-flow LVAD at time of HT between January 1, 2000 and June 30, 2015. Patients with pulsatile ventricular assist devices were not included in the analysis.

We excluded patients who received multiorgan transplants or had missing ARF or CKD data on renal function in the Registry. When evaluating CKD as an outcome, we also excluded patients who did not survive to discharge from the index hospitalization.

Definitions and Outcomes

We evaluated a number of variables included in the ISHLT TTX Registry.22 These included patient-level demographics, comorbidities, laboratory values, hemodynamics, operative factors, and medications. Use of LVAD support was also an independent variable in certain analyses.

Outcome definitions were based on data available in the Registry.22 Acute renal failure was defined as treatment with post-transplant dialysis during the index hospitalization. Chronic kidney disease was defined as creatinine >2.5 mg/dl, permanent dialysis, or renal transplantation following discharge after the heart transplant. A follow-up period up to 3 years after HT was evaluated.

Statistical Analysis

In evaluation of baseline characteristics for continuous variables, the number of observations, median values, and 25th and 75th percentiles were reported. For categorical variables, number of observations and distribution of values was reported. Comparisons between groups by LVAD support were done using Wilcoxon rank sum test for continuous variables and χ2 or Fisher’s exact test for categorical variables.

For assessment of ARF requiring HD, a χ2 test was used to determine differences in outcomes by LVAD support. To account for competing risk of mortality in a sensitivity analysis, the percentage of death was also compared between groups. We constructed a multivariable logistic regression model for acute kidney injury (AKI) with prespecified covariates, including use of LVAD support as an independent variable. The other covariates included age, sex, body mass index (BMI), pretransplant diabetes mellitus (DM), etiology of cardiomyopathy, baseline estimated glomerular filtration rate (eGFR), serum bilirubin, cardiac index, transpulmonary gradient, ischemic time, and induction therapy use. We also constructed a multivariable logistic regression model for ARF requiring HD using prespecified covariates only in patients with LVAD support at time of HT. Odds ratios (OR) for significant variables were assessed.

The cumulative incidence of CKD within 3 years post-transplant, stratified by LVAD support, was estimated using the Kaplan-Meier extension as described by Fine and Gray to account for the competing risk of mortality.23 We then performed a multivariable Cox regression analysis with prespecified covariates including use of LVAD support. The other covariates included age, sex, BMI, pretransplant DM, etiology of cardiomyopathy, baseline eGFR, serum bilirubin, serum albumin, ischemic time, calcineurin inhibitor (CNI) use, post-HT–treated acute rejection before discharge, and post-HT dialysis before discharge. Additionally, a multivariable Cox regression model using prespecified covariates for CKD was performed only for patients with LVAD support at time of HT. Hazard ratios (HRs) for significant variables were evaluated.

For the multivariable analyses, missing values for risk factors were imputed using multiple imputation method (n = 61).24 Continuous risk factors were modeled as restricted cubic splines with three knots, to allow for the most flexible fit of the functional form.

A p value <0.05 was considered statistically significant. Statistical analyses were performed using SAS v9.3 (SAS Institute, Inc., Cary, NC) and R Version 3.5.0 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Baseline Characteristics

A total of 22,345 adult patients underwent deceased donor heart alone transplantation in the ISHLT TTX Registry between January 1, 2000 and June 30, 2015. Of these, 913 were excluded for missing data on ARF leaving a cohort of 21,432 patients for the ARF analysis. From this group, 5,038 (24%) patients were bridged to HT with durable LVAD support.

Furthermore, 587 patients did not survive to discharge of index hospitalization and 2,107 patients had missing data on CKD. After these patients were excluded, a cohort of 18,738 patients was used for the CKD analysis. Among this group, there were 4,535 (24%) LVAD patients (Figure 1).

F1
Figure 1.:
Study diagram of the inclusion/exclusion criteria to generate the acute kidney injury and CKD cohorts. ARF, acute renal failure; CKD, chronic kidney disease; HD, hemodialysis; HT, heart transplantation; ISHLT, International Society for Heart and Lung Transplantation; LVAD, left ventricular assist device.

Baseline characteristics are shown in Table 1. There were several significant differences between groups in terms of comorbidities, etiology of heart disease, laboratory values, hemodynamics, operative factors, and post-HT characteristics. Most notably, patients with durable LVAD were more likely to be male (81% vs. 72%, p < 0.001), have higher BMI (28.0 vs. 26.2, p < 0.001), have higher prevalence of DM (31% vs. 24%, p < 0.001), more likely to have ischemic and nonischemic cardiomyopathy relative to other forms, have higher baseline eGFR (84.9 vs. 75.5, p < 0.001), and increased use of tacrolimus. Furthermore, 3,751 (82.7%) patients had HeartMate II device, 713 (15.7%) had HeartWare HVAD device, and 71 (1.6%) had Jarvik 2000 device.

Table 1. - Baseline Characteristics
Variable Durable LVAD (n = 4,535) No Durable LVAD (n = 14,203) p Value
Age (years) 56.0 (47.0, 62.0) 55.0 (46.0, 62.0) 0.064
Male sex 3,659 (81%) 10,252 (72%) <0.001
Body mass index (kg/m2) 28.0 (24.6, 31.7) 26.2 (23.1, 29.6) <0.001
Diabetes mellitus 1,388 (31%) 3,434 (24%) <0.001
Etiology <0.001
 Nonischemic cardiomyopathy 2,441 (54%) 6,158 (43%)
 Ischemic cardiomyopathy 1,908 (42%) 5,546 (39%)
 Hypertrophic cardiomyopathy 48 (1.1%) 449 (3.2%)
 Restrictive cardiomyopathy 40 (0.9%) 482 (3.4%)
 Valvular cardiomyopathy 45 (1.0%) 399 (2.8%)
 Congenital heart disease 26 (0.6%) 488 (3.4%)
 Retransplant 5 (0.1%) 528 (3.7%)
 Other 22 (0.5%) 153 (1.1%)
Labs
 Estimated GFR (ml/min) 84.9 (65.6, 109.9) 75.5 (57.8, 97.9) <0.001
 Serum bilirubin (mg/dl) 0.7 (0.5, 1.0) 0.8 (0.5, 1.3) <0.001
 Serum albumin (g/dl) 3.7 (3.2, 4.1) 3.8 (3.4, 4.2) <0.001
Hemodynamics
 Cardiac index (L/min/m2) 2.3 (1.9, 2.8) 2.2 (1.8, 2.7) <0.001
 Transpulmonary gradient (mm Hg) 9.0 (7.0, 12.0) 9.0 (6.0, 12.0) 0.001
Ischemic time (hrs) 3.2 (2.5, 3.9) 3.2 (2.4, 3.8) 0.007
Post-HT inotropes before discharge (days) 6.0 (4.0, 8.0) 5.0 (3.0, 7.0) <0.001
Induction therapy 2,243 (49.7%) 7,430 (52.7%) 0.001
Calcineurin inhibitor use <0.001
 Tacrolimus 4,042 (90%) 9,856 (71%)
 Cyclosporine 366 (8.1%) 3,761 (27.0%)
 None 85 (1.9%) 327 (2.3%)
Post-HT–treated acute rejection before discharge 464 (10.2%) 1,444 (10.2%) 0.920
Post-HT dialysis before discharge 331 (7.3%) 900 (6.3%) 0.023
LVAD device type
 HeartMate II 3,751 (82.7%)
 HeartWare HVAD 713 (15.7%)
 Jarvik 2000 71 (1.6%)
Continuous variables are presented as median (25th, 75th percentile).
GFR, glomerular filtration rate; HT, heart transplantation; LVAD, left ventricular assist device.

Incidence of Post-Heart Transplantation Acute Renal Failure Requiring Hemodialysis and Chronic Kidney Disease

The incidence of ARF requiring HD following HT was significantly higher in patients bridged with a durable LVAD compared with non-LVAD patients (9.6% vs. 8.1%, p < 0.001) (Table 2). In our sensitivity analysis to account for death as a competing risk, there was no significant difference in death before discharge in durable LVAD patients relative to non-LVAD patients (1.7% vs. 1.6%, p = 0.528). In a multivariable analysis, patients bridged with a durable LVAD had a 35% higher odds for development of post-HT ARF requiring HD compared to non-LVAD patients (OR = 1.35, 95% CI, 1.16–1.59, p < 0.001) when accounting for other clinical characteristics (Table 1, Supplemental Digital Content 1, https://links.lww.com/ASAIO/A700).

Table 2. - Incidence of Post-HT ARF Requiring HD
Outcome Durable LVAD (n = 5,038) (%) No Durable LVAD (n = 16,394) (%) p Value
ARF requiring HD at discharge 484 (9.6) 1,331 (8.1) <0.001
Death at discharge 87 (1.7) 262 (1.6) 0.528
Death or ARF requiring HD at discharge 643 (12.8) 1,759 (10.7) <0.001
ARF, acute renal failure; HD, hemodialysis; HT, heart transplantation; LVAD, left ventricular assist device.

Left ventricular assist device patients had significantly higher incidence of CKD at 1 year compared with patients without LVAD (7.0% vs. 5.7%, p = 0.002) when accounting for the competing risk of death (Table 3). However, patients with and without durable LVAD did not have significantly different incidence of CKD at 3 years (10.9% vs. 10.2%, p = 0.118). Furthermore, when adjusting for baseline characteristics in a multivariable analysis, LVAD patients were not at significantly higher risk of CKD at 3 years than non-LVAD patients (OR = 1.11, 95% CI, 0.99–1.25, p = 0.064; Table 2, Supplemental Digital Content 1, https://links.lww.com/ASAIO/A700).

Table 3. - Cumulative Incidence of Post-HT CKD
Outcome Durable LVAD (n = 4,535) (95% CI) No Durable LVAD (n = 14,203) (95% CI) p Value
CKD at 1 year 7.0% (6.3%–7.7%) 5.7% (5.4%–6.1%) 0.002
CDK at 3 years 10.9% (10.1%–11.9%) 10.2% (9.7%–10.7%) 0.118
CI, confidence interval; CKD, chronic kidney disease; HT, heart transplantation; LVAD, left ventricular assist device.

Risk Factors for Post-Heart Transplantation Acute Renal Failure Requiring Hemodialysis in Left Ventricular Assist Device Patients

Among patients with durable LVAD support, there were multiple risk factors for post-HT ARF requiring HD identified in a multivariable analysis (Table 4). In particular, higher BMI (OR = 1.79, 95% CI, 1.45–2.20, p < 0.001), lower estimated GFR at transplant (OR = 0.43, 95% CI = 0.34–0.54, p < 0.001), and longer ischemic time (OR = 1.28, 95% CI = 1.06–1.55, p = 0.014) were significant risk factors for post-HT ARF requiring HD in durable LVAD patients (Figure 2). Risk of post-HT AKI increased with higher BMI, longer ischemic time, and lower baseline estimated GFR in a continuous manner (Figure 3). No induction therapy was also associated with a lower risk of post-HT ARF requiring HD (OR = 0.70, 95% CI = 0.54–0.90, p = 0.005).

Table 4. - Risk Factors for Post-HT ARF Requiring HD in LVAD Patients (n = 4,535)
Variable Odds Ratio (95% CI) p Value
Age (years): 62 vs. 47 0.82 (0.65–1.05) 0.204
Male sex 1.12 (0.81–1.56) 0.487
Body mass index (kg/m2): 31.7 vs. 24.6 1.79 (1.45–2.20) <0.001
Diabetes mellitus 1.09 (0.84–1.43) 0.5115
Etiology (vs. NICM)
 Ischemic cardiomyopathy 1.19 (0.90–1.56) 0.218
 Hypertrophic cardiomyopathy 2.25 (0.85–5.95) 0.103
 Restrictive cardiomyopathy 1.83 (0.61–5.49) 0.282
 Valvular cardiomyopathy 1.62 (0.55–4.77) 0.385
 Congenital heart disease 2.22 (0.47–10.50) 0.314
Labs
 Estimated GFR (ml/min): 110 vs. 66 0.43 (0.34–0.54) <0.001
 Serum bilirubin (mg/dl): 1.00 vs. 0.50 0.98 (0.80–1.22) 0.794
Hemodynamics
 Cardiac index (L/min/m2): 2.78 vs. 1.91 0.92 (0.77–1.10) 0.633
 Transpulmonary gradient (mm Hg): 12.0 vs. 7.0 0.95 (0.81–1.11) 0.802
Ischemic time (hrs): 3.90 vs. 2.47 1.28 (1.06–1.55) 0.014
No induction therapy 0.70 (0.54–0.90) 0.005
Odds ratios for continuous variables are shown for third quartile compared with first quartile.
ARF, acute renal failure; GFR, glomerular filtration rate; HD, hemodialysis; HT, heart transplantation; LVAD, left ventricular assist device; NICM, nonischemic cardiomyopathy.

F2
Figure 2.:
Forest plot of significant risk factors for post-transplant acute renal failure requiring hemodialysis in left ventricular assist device patients. Odds ratio for continuous variables are shown for third quartile compared to first quartile. BMI, body mass index; CI, confidence interval; eGFR, estimated glomerular filtration rate.
F3
Figure 3.:
Significant continuous risk factors for post-transplant acute renal failure requiring hemodialysis in left ventricular assist device patients including (A) recipient BMI, (B) baseline estimated glomerular filtration rate, and (C) total ischemic time demonstrate dose-response association. BMI, body mass index; eGFR, estimated glomerular filtration rate.

Risk Factors for Post-Heart Transplantation Chronic Kidney Disease in Left Ventricular Assist Device Patients

In patients with durable LVAD support, a multivariable analysis showed multiple significant risk factors for post-HT CKD within 3 years (Table 5). Specifically, higher BMI (HR = 1.49, 95% CI = 1.23–1.79, p < 0.001) and lower estimated GFR at transplant (HR = 0.41, 95% CI = 0.33–0.50, p < 0.001), presence of pretransplant DM (HR = 1.37, 95% CI = 1.07–1.75, p = 0.011), and treatment with post-HT dialysis before discharge from index hospitalization (HR = 3.93, 95% CI = 2.98–5.19, p < 0.001) were significant risk factors for post-HT CKD at 3 years (Figure 4). Risk of CKD increased as BMI increased and baseline estimated GFR decreased in a continuous manner (Figure 5).

Table 5. - Risk Factors for Post-HT CKD at 3 Years in LVAD Patients (n = 4,535)
Variable Hazard Ratio (95% CI) p Value
Age (years): 62.0 vs. 47.0 0.92 (0.74–1.13) 0.697
Male sex 1.15 (0.84–1.56) 0.387
Body mass index (kg/m2): 31.7 vs. 24.6 1.49 (1.23–1.79) <0.001
Diabetes mellitus 1.37 (1.07–1.75) 0.011
Etiology (vs. NICM)
 Ischemic cardiomyopathy 1.13 (0.88–1.45) 0.335
 Hypertrophic cardiomyopathy 0.76 (0.18–3.09) 0.698
 Restrictive cardiomyopathy 0.43 (0.06–3.10) 0.403
 Valvular cardiomyopathy 0.61 (0.15–2.46) 0.485
 Congenital heart disease 2.45 (0.58–10.40) 0.223
 Retransplant or other 1.08 (0.15–7.83) 0.942
Labs
 Estimated GFR (ml/min): 110 vs. 66 0.41 (0.33–0.50) <0.001
 Serum bilirubin (mg/dl): 1.00 vs. 0.50 1.01 (0.83–1.23) 0.663
 Serum albumin (g/dl): 4.10 vs. 3.20 0.97 (0.81–1.15) 0.785
Ischemic time (hrs) - 3.90 vs. 2.47 1.02 (0.86–1.20) 0.9740
Calcineurin inhibitor use (vs. tacrolimus)
 Cyclosporine 1.34 (0.94–1.92) 0.106
 None 1.50 (0.81–2.81) 0.200
Post-HT days on inotrope before discharge: 8.0 vs. 4.0 1.03 (0.85, 1.25) 0.597
Post-HT–treated acute rejection before discharge 1.02 (0.70, 1.50) 0.909
Post-HT dialysis before discharge 3.93 (2.98–5.19) <0.001
Hazard ratios for continuous variables are shown for third quartile compared with first quartile.
CKD, chronic kidney disease; GFR, glomerular filtration rate; HT, heart transplantation; LVAD, left ventricular assist device; NICM, nonischemic cardiomyopathy.

F4
Figure 4.:
Forest plot of significant risk factors for post-heart transplant chronic kidney disease in left ventricular assist device patients. Hazard ratios for continuous variables are shown for third quartile compared to first quartile. BMI, body mass index; eGFR, estimated glomerular filtration rate; Tx, transplant.
F5
Figure 5.:
Significant continuous risk factors for post-transplant chronic kidney disease in left ventricular assist device patients including (A) recipient BMI and (B) baseline glomerular filtration rate demonstrate dose-response association. BMI, body mass index; eGFR, estimated glomerular filtration rate.

Discussion

In this registry-based analysis of patients who underwent HT, we demonstrated that patients bridged with durable LVAD had higher incidence of ARF requiring HD and early CKD within 1 year compared with non-LVAD patients. Patients with LVAD support were demonstrated to be at 35% increased risk of post-HT ARF requiring HD when accounting for other potentially associated risk factors. However, patients bridged with and without durable LVAD had similar rates of late CKD by 3 years after HT. Incidence of death at discharge from index hospitalization was similar between groups, making survival bias less likely to account for the difference in rates of ARF requiring HD post-HT. Similarly, a competing risk analysis confirmed the rates of CKD at 3 years post-HT were similar when accounting for competing risk of death.23

Left ventricular assist device patients bridged to HT have different comorbidities, operative factors, and hemodynamic profiles compared with non-LVAD patients.12–16,25 Estimated GFR generally improves after LVAD implantation due to improved renal perfusion.17,26 In our cohort, LVAD patients had higher GFR before HT compared with non-LVAD patients. However, LVAD patients were more often male, had higher BMI, and were more likely to have DM. An increased burden of comorbidities and other associated conditions not included in the Registry (e.g., hypertension) could predispose LVAD patients to higher risk of ARF requiring HD and early CKD compared with non-LVAD patients.

Although ischemic time did not have a clinically relevant difference between groups, LVAD patients undergoing HT typically have longer cardiopulmonary bypass times, lower hemoglobin counts, and higher perioperative blood transfusion requirements compared with non-LVAD patients.27,28 These risk factors could also be associated with higher incidence of ARF requiring HD and CKD at 1 year in LVAD patients.19,21,29–31 Unfortunately, these additional variables were not available in the Registry.

Notably, LVAD patients had higher incidence of ARF requiring HD and early CKD, even though patients with temporary mechanical circulatory support (MCS) were included in the non-LVAD group. Several prior studies have demonstrated that temporary MCS is not significantly associated with post-HT renal dysfunction, potentially because it may not have the same comorbidity burden and effect on perioperative factors as durable LVAD patients.8,10,21

The differences in development of CKD by 3 years between the two groups became attenuated, as risk was likely more attributable to other factors present after HT such as the use of CNI and comorbidities including hypertension, DM, and obesity.7,19

In considering LVAD patients specifically, the most significant risk factors for AKI were higher BMI, lower baseline estimated GFR at transplant, longer ischemic time, and use of induction therapy. Prior studies have shown that these risk factors, among others, have been associated with AKI including post-HT dialysis.8,10,19,21 Similar to our findings, Kilic et al.21 demonstrated that BMI, estimated GFR, and ischemic time were associated with post-HT ARF requiring HD with a dose-responsive relationship in 14,635 patients that underwent HT including 21% bridged with LVAD support.21 Recipient age, etiology of HF, serum bilirubin, and DM were also significantly associated with ARF requiring HD in the previous study. These factors were not significant in our study, potentially due to a lesser effect in LVAD patients.21 Thus, although LVAD patients are at increased risk for post-HT ARF requiring HD compared with non-LVAD patients, the risk factors for post-HT ARF requiring HD in LVAD patients are largely similar to risk factors in all patients undergoing HT.

Significant risk factors for CKD at 3 years in LVAD patients undergoing HT include pretransplant DM, baseline estimated GFR, BMI, and post-HT dialysis before discharge from index hospitalization. These risk factors have been associated with post-HT CKD in prior studies in non-LVAD patients. For instance, Ojo et al.7 analyzed over 24,000 HT recipients and showed the same risk factors were significantly associated with CKD. Of note, that study showed recipient age, male sex, preoperative hypertension, and hepatitis C were also risk factors for CKD.7 Our analysis in LVAD patients showed these variables were either insignificant or unavailable. Interestingly, CNI use was not significantly associated with CKD in our analysis or the prior study, which may partly be due to confounding by indication, as CNI may be used less frequently in patients with post-HT renal dysfunction.7 Overall, risk factors for post-HT CKD in LVAD patients are mostly similar to risk factors in all patients undergoing HT.

Mechanistically, there are various reasons for why these risk factors are associated with renal dysfunction. Patients with worse baseline renal dysfunction are more likely to develop ARF requiring HD and CKD as a result of additional peri-transplant insults.32 Higher BMI is associated with several comorbidities, such as hypertension and diabetes. In addition, obesity activates the renin-angiotensin-aldosterone axis, promotes oxidative stress, and increases glomerular capillary hypertension, which can contribute to renal dysfunction.33–35 Longer ischemic time is correlated with increased cardiopulmonary bypass time, which leads to renal ischemic and reperfusion injury, hemolysis and pigment nephropathy, oxidative stress, and an inflammatory response.30 In addition, higher ischemic time can cause primary cardiac graft dysfunction, which in turn can increase risk of AKI including need for HD.10,25 Diabetes mellitus, which can develop or worsen following HT due to medication effects, causes nodular glomerulosclerosis and contributes to CKD.19 Finally, use of induction therapy was included in the analysis to account for associations with the other covariates and outcomes. However, the significant association with ARF requiring HD in LVAD patients is likely due to confounding by indication, wherein clinicians may use induction therapy more frequently in HT patients at increased risk of renal dysfunction.

There are several limitations to our study. Our analysis was based on the ISHLT TTX Registry and thereby limited to the available data. Notably, LVAD and non-LVAD patients who undergo HT have important differences, as discussed previously. Certain relevant covariates such as hypertension, cardiopulmonary bypass time, blood cell counts, blood transfusion requirements, and specifics on graft dysfunction were unavailable for analysis. Although the Registry uses definitions of ARF and CKD that are clinically relevant, AKI and CKD following HT can have other definitions. Our analysis is limited to the definition used by the Registry.10,22 While the Registry utilizes system quality control measures, missing or inaccurate data may also be present.

Furthermore, the utilization of continuous-flow LVAD as bridge-to-transplant has evolved during the study period with the advent of centrifugal-flow LVADs.36–38 Many of the patient characteristics related to renal dysfunction including baseline renal function, DM, BMI, and ischemic time are unlikely to be affected by LVAD type and likely remain relevant in all patients with continuous-flow LVADs. Furthermore, axial- and centrifugal-flow LVADs have been demonstrated to have relatively similar hemodynamic support, potentially mitigating effect of pump type on post-HT renal dysfunction.39,40 However, surgical techniques differ between axial- and centrifugal-flow LVADs and may affect certain perioperative factors (e.g., ischemic time, cardiopulmonary bypass time, blood product administration) at time of HT. Thus, further investigation in centrifugal-flow LVADs should be considered when datasets with larger sample sizes and longer follow-up time specifically in these devices are available.

Additionally, temporal changes in management of HT patients within the study period may affect the findings. However, multivariate analyses accounted for many of these potential factors (e.g., induction therapy, use of specific CNI agents, ischemic time). Moreover, the significant predictors of renal dysfunction including comorbidities, baseline renal function, and ischemic time would maintain relevance throughout the study period.

Conclusions

In this registry-based study, we demonstrated that HT recipients bridged with LVAD, compared with those without LVAD, have increased incidence of ARF requiring HD and early CKD at 1 year, but similar incidence of late CKD at 3 years. Increased risk of renal dysfunction specifically in LVAD patients seems to be predominantly due to comorbidities and operative factors including higher BMI, worse baseline renal function, longer ischemic time, and presence of DM. Future investigation could more thoroughly evaluate risk factors for renal dysfunction in centrifugal-flow LVAD patients. Furthermore, prospective investigations should more comprehensively evaluate risk factors for AKI and CKD following HT, which may also provide additional mechanistic insights into risk of renal dysfunction. In turn, subsequent steps could evaluate therapeutic strategies to mitigate risk of post-HT renal dysfunction by intervening on specific modifiable risk factors or selecting high-risk LVAD patients for combined heart-kidney transplant.

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Keywords:

left ventricular assist device; heart transplantation; acute kidney injury; chronic kidney injury; renal dysfunction

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