Acute Renal Failure after Lung TransplantationDocument Transcript
American Journal of Transplantation 2005; 5: 1469–1476 Copyright C Blackwell Munksgaard 2005
Acute Renal Failure after Lung Transplantation:
Incidence, Predictors and Impact on Perioperative
Morbidity and Mortality
Paulo N. Rochaa, ∗ , Ana T. Rochab , Scott M. Introduction
Palmerb , R. Duane Davisc and Stephen R. Smitha
In the 2 decades since the performance of the ﬁrst suc-
Duke University Medical Center, Departments of cessful lung transplant (LT) by the Toronto group (1), lung
Medicine and Surgery, Divisions of a Nephrology, transplantation (LTx) has become the preferred treatment
Pulmonology and c Cardiothoracic Surgery, Durham, NC modality for patients with end-stage pulmonary disease
17710, USA (2,3). According to the 21st annual registry of the Inter-
∗ Corresponding author: Paulo N. Rocha,
national Society for Heart and Lung Transplantation, 1655
email@example.com LTs were performed worldwide in the year 2002 (4). A sig-
niﬁcant proportion of these patients develop chronic renal
The incidence, predictors and clinical signiﬁcance of dysfunction after LTx (5,6), a phenomenon frequently at-
acute renal failure (ARF) after lung transplantation tributed to the toxicity of calcineurin inhibitors. However,
are not well described. We retrospectively collected data on the incidence and clinical implications of acute renal
data on 296 patients transplanted at our center be- failure (ARF) following LTx are scarce.
tween April 1992 and December 2000; follow-up was
extended until December 2002. Patients were initially
divided into two groups: ARF (doubling of baseline cre- Several factors peculiar to LTx might act in synergism to
atinine within 2 weeks after surgery) and NoARF. The place recipients at increased risk for ARF. First, it has been
ARF group was subdivided into ARFD (dialyzed) and suggested that patients with respiratory failure may experi-
ARFnD (not dialyzed). The incidence of ARF was 56% ence renal hypoperfusion (7,8), which could potentiate the
(166/296), but most cases were ARFnD (n = 143). In- nephrotoxic effects of hemodynamic instabilities that may
dependent predictors of ARFD (n = 23) were: baseline occur during thoracic surgery. Second, the calcineurin in-
GFR (OR 0.98, CI 0.96–0.99, p = 0.012), pulmonary di- hibitors used in the immediate postoperative period cause
agnosis other than COPD (OR 6.80, CI 1.5–30.89, p = renal vasoconstriction and reduce renal perfusion (9–11).
0.013), mechanical ventilation > 1 d (OR 6.16, CI 1.70– Third, the ‘leaky capillaries’ of freshly transplanted lungs
22.24, p = 0.006) and parenteral amphotericin B use
lead to the use of diuretics to reduce pulmonary edema,
(OR 3.04, CI 1.03–8.98, p = 0.045). Both ARFnD and
ARFD were associated with longer duration of me- which may, in turn, decrease circulating blood volume and
chanical ventilation, increased hospital stay and in- further aggravate renal hypoperfusion. The intense renal
creased early mortality. One-year patient survival was vasoconstriction that ensues might then augment the risk
92.3%, 81.8% and 21.7% in the NoARF, ARFnD and of ARF caused by antibiotics, antifungals and antivirals that
ARFD groups, respectively (p < 0.0001). After control- are frequently used in this setting.
ling for important covariates, ARFD remained associ-
ated with an increased hazard of dying (HR 6.77, CI Navis and coworkers studied the renal hemodynamics be-
4.00–11.44, p < 0.0001). In conclusion, ARF occurs com-
fore and after LTx in 44 patients and showed that a reduc-
monly after lung transplantation and affects important
clinical outcomes, especially when dialysis is required. tion in glomerular ﬁltration rate (GFR) could be detected
as early as 1 month postoperatively (8). In a subsequent
Key words: Acute renal failure, amphotericin B, dialy- report, the same group showed that the long-term renal
sis, lung transplantation, mechanical ventilation, risk outcome following LTx could be predicted by the 1-month
factors GFR (12). More recently, Ishani et al. documented a decline
in renal function in 91.3% of lung or combined heart–lung
Received 7 November 2004, revised 3 January 2005 and transplant recipients by 6 months (13). However, none of
accepted for publication 19 January 2005 these studies examined ARF occurring immediately after
surgery. Therefore, the incidence, predictors and impact
of ARF on perioperative morbidity and mortality after LTx
are presently unknown. To address these issues, we con-
This work was presented as a mini oral session at the 2004 Amer- ducted a retrospective review of 296 consecutive patients
ican Transplant Congress, Boston, MA. that underwent LTx at our center over an 8-year period.
Rocha et al.
Materials and Methods Retrospective review of all lung transplants
performed at DUMC between 4/92 – 12/00
Study design, inclusion and exclusion criteria
We performed a retrospective cohort study using a convenience sample. All
N = 312 transplants Excluded:
consecutive patients that underwent LTx at Duke University Medical Cen-
ter (DUMC) between April 1992 (ﬁrst LT performed at DUMC) and Decem-
Died within 24 hours
ber 2000 (n = 312) were included. Combined heart–lung transplants were
N = 296 patients Missing critical data
not included. Retransplants (n = 10), recipients that died within the ﬁrst
24 hours (n = 5) and those for whom critical data were missing (n = 1)
were excluded. The remaining 296 patients comprised our study group. Follow-up extended until 12/02
Data acquisition was extended until December 2002 to allow for at least
2 years (maximum of 10 years) of follow-up.
Mean follow-up = 3.3 ± 2.4 years
Data acquisition ARFnD
Information on patient demographics, predictor variables and outcomes of N = 143
interest were obtained from electronic medical records and clinic paper NoARF ARF
charts. All cyclosporine A (CsA) levels obtained within the ﬁrst week and N = 130 N = 166
all serum creatinine levels obtained within the ﬁrst 2 weeks of LTx were N = 23
collected. We also collected follow-up data on serum creatinine and CsA
levels for three clinic visits during the ﬁrst year posttransplant (ﬁrst visit
postdischarge, then 3 and 12 months later) and yearly thereafter. Figure 1: Study ﬂow chart. Retrospective review of all LTs per-
formed at Duke University Medical Center between April 1992 and
December 2000. Two hundred ninety-six patients were identiﬁed
and mean follow-up for the entire group was 3.3 ± 2.4 years. Most
ARF was deﬁned according to the RIFLE criteria (acronym indicating Risk
patients (n = 166) had ARF, but only a minority (n = 23) required
of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of
kidney function and End-stage kidney disease) (14). We used the RIFLE-I
criterion (injury) of doubling of the baseline serum creatinine within the ﬁrst
2 weeks of LTx. Patients who did not meet this criterion comprised the
NoARF group. The ARF group was further divided into ARFD (dialyzed) and (Figure 1). One hundred sixty-six patients (56%) experi-
ARFnD (not dialyzed). GFR was estimated using the abbreviated Modiﬁ- enced ARF approximately 1 week (7.3 ± 3.8 d) after LTx.
cation of Diet in Renal Disease study equation (15). Estimated GFR was The majority of these cases, however, were not dialyzed
deﬁned as normal (≥ 90 mL/min/1.73 m2 ), decreased (60–89 mL/min/1.73 (ARFnD, n = 143). The incidence of ARF requiring dialysis
m2 ), or consistent with chronic kidney disease (CKD, GFR < 60 mL/min/1.73 was 8% (ARFD, n = 23).
m2 ) according to recently published guidelines (16).
The mean age for the entire population was 47 ± 14 years.
Statistical analysis Interestingly, mean age was signiﬁcantly lower in the
Data were summarized with mean ± standard deviation (SD) or median
ARFnD than in the NoARF group (44 ± 15 vs. 51 ± 13,
and interquartile range (IQR). Continuous variables were compared among
p = 0.0007); ARFD patients were also younger than those
groups using ANOVA or the Kruskal–Wallis test; post hoc multiple com-
parisons were performed using Bonferroni or Dunnett’s T3 methods. Pro-
without ARF, but this difference was not statistically sig-
portions were compared using the chi-square or Fisher’s exact test. Logis- niﬁcant (Table 1). The majority of patients studied were
tic regression analyses were performed to identify covariates associated white (90%). However, 30% of those who required dialy-
with ARFD. Covariates assessed on univariate analyses were: age, race, sis for ARF were non-white. The racial distribution of pa-
underlying pulmonary diagnosis, type of LT, pre-LT diabetes mellitus, pre- tients in the three outcome groups was thus signiﬁcantly
LT hypertension, baseline GFR, duration of mechanical ventilation (MV), different at the p = 0.002 level. The most common pul-
antimicrobials and diuretics used perioperatively. A multivariate analysis monary diagnoses leading to transplantation were chronic
with backward selection was then performed to identify covariates inde- obstructive pulmonary disease (COPD, 45%), cystic ﬁbro-
pendently associated with ARFD. Patient mortality was analyzed using the
sis (CF, 21%) and idiopathic pulmonary ﬁbrosis (IPF, 10%).
Kaplan–Meier method and survival curves were compared using the log-
This order of frequency was maintained in the NoARF and
rank test. The effect of different covariates on mortality was evaluated
using Cox proportional-hazards models. Variables assessed on univariate
ARFnD groups, but not in the ARFD group. In this latter
analyses were: age, underlying pulmonary diagnosis, race, type of LT, gen- group, pulmonary hypertension and IPF were the predom-
der and ARFD. Variables that achieved statistical signiﬁcance on univariate inant diagnoses (22% each), followed by sarcoidosis, a1
analysis were included in a multivariate model to identify independent pre- antitrypsin and CF (13% each). In addition, COPD was a rel-
dictors of mortality. Statistical analyses were performed using SAS (version atively uncommon diagnosis (9%) among ARFD patients.
8.2) and SPSS (version 13.0). p-values <0.05 were considered statistically Overall, bilateral LTx was the most common surgical proce-
signiﬁcant. dure (53%), but a disproportionately high frequency of bilat-
eral LTx was performed in patients who developed ARFD
Results (83%). Mean preoperative GFR was 103 ± 39 mL/min/1.73
m2 . Baseline GFR varied signiﬁcantly with pulmonary di-
The study group consisted of 296 patients transplanted agnosis, with the highest values encountered in CF and
over an 8-year period and followed up for 3.3 ± 2.4 years the lowest in pulmonary hypertension (135 ± 51 vs.
1470 American Journal of Transplantation 2005; 5: 1469–1476
Acute Renal Failure after Lung Transplantation
Table 1: Baseline characteristics
Baseline variables NoARF (n = 130) ARFnD (n = 143) ARFD (n = 23) p-value
Age, years (mean ± SD) 51 ± 131,2 44 ± 153 45 ± 12 0.0009
Male 57% (74) 48% (68) 48% (11) 0.28
Female 43% (56) 52% (75) 52% (12)
White 94% (122) 90% (128) 70% (16) 0.002
Non-white 6% (8) 11% (15) 30% (7)
COPD 59% (77) 38% (55) 9% (2) <0.0001
Cystic ﬁbrosis 12% (15) 30% (43) 13% (3)
Idiopathic pulmonary ﬁbrosis 10% (13) 9% (13) 22% (5)
a1-antitrypsin 6% (8) 5% (7) 13% (3)
Pulmonary hypertension 5% (6) 4% (6) 22% (5)
Sarcoidosis 2% (3) 5% (7) 13% (3)
Bronchiectasis 3% (4) 2% (3) 4% (1)
Others 3% (4) 6% (9) 4% (1)
Type of lung transplant
Right lung 25% (32) 12% (17) 4% (1) 0.0003
Left lung 35% (56) 29% (41) 13% (3)
Bilateral 40% (42) 59% (85) 83% (19)
Pretransplant medical conditions
Diabetes mellitus 3% (4) 3% (5) 13% (3) 0.07
Systemic hypertension 25% (32) 28% (40) 35% (8) 0.56
Baseline creatinine, mg/dL 0.884,5 ± 0.22 0.776 ± 0.21 0.97 ± 0.23 <0.0001
Baseline GFR, mL/min/1.73 m2 95 ± 327,8 113 ± 429 87 ± 28 <0.0001
GFR categories (in mL/min/1.73 m2 )
Normal (≥90) 53% (69) 71% (102) 35% (8) 0.0002
Decreased (60–89) 41% (53) 28% (40) 52% (12)
CKD (<60) 6% (8) 1% (1) 13% (3)
Percentages may not add up to 100% due to rounding. COPD = chronic obstructive pulmonary disease; GFR = glomerular ﬁltration rate;
CKD = chronic kidney disease.
1 p = 0.0007 for NoARF vs. ARFnD; 2 p = 0.2491 for NoARF vs. ARFD; 3 p = 1.0 for ARFnD vs. ARFD; 4 p = 0.0002 for NoARF vs. ARFnD;
5 p = 0.1375 for NoARF vs. ARFD; 6 p = 0.0001 for ARFnD vs. ARFD; 7 p = 0.0002 for NoARF vs. ARFnD; 8 p = 1.0 for NoARF vs. ARFD;
9 p = 0.0067 for ARFnD vs. ARFD.
77 ± 15 mL/min/1.73 m2 , p < 0.0001). Interestingly, and ARFD (182 ± 53 ng/mL) groups, respectively. Antivi-
patients who developed ARF had higher preoperative rals and diuretics were commonly used in the immedi-
GFR than patients who did not (110 ± 42 vs. 95 ± 33 ate postoperative period; utilization of these drugs was
mL/min/1.73 m2 , p = 0.001). This apparent contradiction similar among the groups. Aminoglycoside and parenteral
was due to the high baseline GFR of ARFnD patients (113 ± amphotericin B, however, were more commonly used by
42 mL/min/1.73 m2 ); patients who developed ARFD ac- patients who developed ARF. Combined use of aminogly-
tually had the lowest baseline GFR of all groups studied. coside and amphotericin B was not common; we only
Other variables such as height, weight, body mass index had four patients that used both drugs concomitantly.
and the presence of diabetes mellitus or systemic hyper- Interestingly, all developed ARF (two ARFnD and two
tension were similar among groups. ARFD).
CsA was the initial calcineurin inhibitor used by 95% of pa- Two hundred four patients had at least one episode of
tients (n = 278) (Table 2). In the year 2000, we moved biopsy-proven acute lung rejection (ALR) during follow-up
to tacrolimus as the primary agent based on accumu- (mean 1.6 ± 1.7 episodes/patient). The median time to the
lated data for its improved efﬁcacy in LTx; this change in ﬁrst ALR episode was 29 (IQR 18–84) d. To investigate a
protocol accounts for the remaining 5% of patients who possible relationship between ALR and ARF, we stratiﬁed
were started on tacrolimus. During follow-up, 33% of pa- ALR episodes into those occurring within (≤14 d) or after
tients (n = 92) were converted from CsA to tacrolimus. the ﬁrst 2 weeks (>14 d). The incidence of ALR in the ﬁrst
Somewhat surprisingly, mean CsA levels during the ﬁrst 2 weeks of LTx was similar among groups (11.5%, 11.9%
week after LTx were highest in the NoARF group (244 and 13% in the NoARF, ARFnD and ARFD groups, respec-
± 57 ng/mL), followed by the ARFnD (222 ± 51 ng/mL) tively; p = NS).
American Journal of Transplantation 2005; 5: 1469–1476 1471
Rocha et al.
Table 2: Posttransplant characteristics
Postoperative variables NoARF (n = 130) ARFnD (n = 143) ARFD (n = 23) p-value
Initial choice of calcineurin inhibitor
Cyclosporine A (CsA) 89% (116) 85% (121) 91% (21) 0.43
Tacrolimus (FK506) 11% (14) 15% (22) 9% (2)
CsA to FK506 conversion during follow-up 25% (29) 35% (38) 25% (2) 0.25
Average CsA level during 1st week 244 ± 571,2 222 ± 513 182 ± 53 <0.0001
Ganciclovir 87% (113) 87% (124) 96% (22) 0.47
Acyclovir 12% (15) 15% (21) 4% (1) 0.34
Tobramycin 6% (8) 25% (36) 13% (3) <0.0001
Amphotericin B 3% (4) 12% (17) 30% (7) <0.0001
Loop diuretics 87% (113) 90% (128) 83% (19) 0.59
Thiazide diuretics 36% (47) 47% (67) 43% (10) 0.20
1p = 0.0009 for NoARF vs. ARFnD; 2 p < 0.0001 for NoARF vs. ARFD; 3 p = 0.0370 for ARFnD vs. ARFD.
Mechanical Ventilation, days
Hospital Stay, days
1 2 13 11 17 35
(1 – 2) (1 – 9) (8 – 28) (8 – 17) (11 – 44) (19 – 95)
NoARF ARFnD ARFD NoARF ARFnD ARFD
Figure 2: Duration of MV and hospital stay according to group distribution. (A) Development of ARF was associated with longer
duration of mechanical ventilation (p < 0.0001 for the comparison among the three groups; p = 0.0263 for NoARF vs. ARFnD; p = 0.0022
for NoARF vs. ARFD; p = 0.124 for ARFnD vs. ARFD). (B) Development of ARF was associated with longer hospital stay (p < 0.0001 for
the comparison among the three groups; p = 0.0148 for NoARF vs. ARFnD; p = 0.0099 for NoARF vs. ARFD; p = 0.0659 for ARFnD vs.
ARFD). Numbers below boxes represent median (IQR).
Typically, recipients were extubated on day 1 after LTx. As in one). Five patients initiated dialysis on CVVHD; in three
shown in Figure 2A, the development of ARF was asso- of these, HD followed CVVHD. Only one patient initiated
ciated with a signiﬁcantly longer stay on MV (p = 0.0263 dialysis on HD.
for ARFnD vs. NoARF; p = 0.0022 for ARFD vs. NoARF).
Duration of hospital stay was similarly affected by the pres- To identify predictor variables associated with ARFD, we
ence of ARF. Overall, the median hospital stay was 15 d. As performed univariate (Table 3, Panel A) and multivariate lo-
shown in Figure 2B, the median hospital stay was 11 (IQR gistic regression analysis. As shown in Panel B of Table 3,
8–17) d for NoARF patients, 17 (IQR 11–44) for ARFnD and the independent predictors of ARFD (n = 23) were: base-
35 (IQR 19–95) d for ARFD patients (p = 0.0148 for ARFnD line GFR (OR 0.98, CI 0.96–0.99, p = 0.012), pulmonary
vs. NoARF; p = 0.0099 for ARFD vs. NoARF). diagnosis other than COPD (OR 6.80, CI 1.5–30.89, p =
0.013), MV > 1 d (OR 6.16, CI 1.70–22.24, p = 0.006) and
Peritoneal dialysis (PD) was the most commonly used parenteral amphotericin B use (OR 3.04, CI 1.03–8.98, p =
dialysis modality, followed by continuous veno–venous 0.045).
hemodialysis (CVVHD) and conventional hemodialysis
(HD). PD was the initial modality used by 17 patients; in There were 55 deaths in the NoARF group (42%), 66
5 of these PD was followed by a second dialysis modality in the ARFnD (46%) and 20 deaths in the ARFD group
(HD in two, CVVHD in one and CVVHD followed by HD (87%) (p = 0.0004). Median times to death were: 792 (IQR
1472 American Journal of Transplantation 2005; 5: 1469–1476
Acute Renal Failure after Lung Transplantation
Table 3: Predictors of ARFD Discussion
Variables OR CI p-value
(A) Univariate logistic regression The main ﬁndings of our study were that ARF occurred
Race (non-white vs. white) 4.76 1.78–12.74 0.002 commonly after LTx (56%), but the majority of episodes
Diagnosis (other vs. COPD) 9.83 2.26–42.71 0.002 did not require dialysis and had a small inﬂuence on peri-
Type of transplant (BL vs. SL) 4.72 1.56–14.22 0.006 operative morbidity and mortality. Conversely, ARFD was
Pretransplant DM (yes vs. no) 4.40 1.10–17.55 0.036 much less common (8%) but greatly affected all clinical
Baseline GFR 0.98 0.96–0.99 0.031 outcomes studied, including mortality.
MV (> 1 vs. ≤ 1 d) 8.01 2.33–27.59 0.001
Amphotericin B (yes vs. no) 5.25 1.94–14.18 0.001
In a study of ARF, the criterion used to deﬁne ARF is directly
related to the incidence encountered. Until recently, how-
(B) Multivariate Logistic Regression
Baseline GFR 0.98 0.96–0.99 0.012 ever, there was no consensus deﬁnition of ARF (17). Given
Diagnosis (other vs. COPD) 6.80 1.50–30.89 0.013 this lack of standardization, it is difﬁcult to compare the inci-
Mechanical ventilation 6.16 1.70–22.24 0.006 dence of ARF encountered herein to that of other studies.
(> 1 vs. ≤ 1 d) The efforts of the Acute Dialysis Quality Initiative Group
Amphotericin B (yes vs. no) 3.04 1.03–8.98 0.045 culminated in the publication of a consensus deﬁnition of
BL = bilateral; SL = single lung; DM = diabetes mellitus; COPD ARF based on the RIFLE criteria (14,18–20). We used the
= chronic obstructive pulmonary disease; GFR = glomerular RIFLE-I criterion of doubling of the baseline serum creati-
ﬁltration rate; MV = mechanical ventilation. nine because it offers a good combination of sensitivity and
speciﬁcity. With this deﬁnition, we found that more than
half (56%) of our patients met criteria for ARF. This is likely
the result of a combination of factors peculiar to LTx: pre-
operative hypoxic respiratory failure, episodes of renal hy-
poperfusion during thoracic surgery, and postoperative use
of calcineurin inhibitors, diuretics and (sometimes) nephro-
toxic antimicrobials. Despite the high incidence of ARF, only
a minority of patients required acute dialysis. This suggests
that most renal insults in this setting are mild and perhaps
caused by reversible hemodynamic-mediated reductions
in GFR. However, we identiﬁed four variables that were in-
dependently associated with ARFD: pulmonary diagnoses
other than COPD, lower baseline GFR, postoperative use
of parenteral amphotericin B and duration of MV greater
than 1 d.
Patients with ‘other’ pulmonary diagnoses had 6.8 greater
Figure 3: Impact of ARF on patient survival. The Kaplan–Meier odds of developing ARFD than patients with COPD. Al-
curves show patient survival over time according to group distribu- though we cannot rule out that unmeasured variables pe-
tion: NoARF (solid line), ARFnD (dashed line), ARFD (dotted line). culiar to certain diagnoses might underlie this observation,
Patient survival in the ARFD group was signiﬁcantly worse than
we believe that the association between pulmonary diag-
in the ARFnD and NoARF groups (p < 0.0001 for the comparison
nosis and ARFD was related, at least in part, to the type of
among the three curves).
surgery performed. In the ARFD group, patients with other
pulmonary diagnoses were much more likely to have re-
ceived bilateral LTx (19/21) than were patients with COPD
595–1192), 531 (IQR 152–1336), 33 (IQR 19–82) in the (0/2). On univariate analysis, bilateral LTx was a strong pre-
NoARF, ARFnD and ARFD, respectively (p < 0.0001). Of dictor of ARFD, but it did not remain in the ﬁnal multivariate
note, 16/20 deaths in the ARFD group occurred during the model likely due to redundancy with underlying diagnosis.
initial hospitalization. A survival analysis is shown in Fig-
ure 3. One-year patient survival was 92%, 82% and 22% A lower baseline GFR was also independently associated
in the NoARF, ARFnD and ARFD groups, respectively (p < with ARFD. This ﬁnding appears to contradict those of
0.0001). At 5 years, patient survival was 61%, 58% and Navis and coworkers who showed pronounced reductions
13%, and at 10 years, 59%, 55% and 13% in the NoARF, in renal function 1 month after LTx in patients with normal
ARFnD and ARFD groups, respectively. In a multivariate or elevated baseline GFR and only modest decreases in
Cox proportional-hazards regression, ARFD (HR 6.77, CI GFR in those with renal impairment prior to surgery (8).
4.00–11.44, p < 0.0001) and single LTx (HR 1.78, CI 1.24– The renal impairment in the latter group was character-
2.55, p = 0.0018) were the only variables independently ized by a marked reduction in renal perfusion, as indicated
associated with an increased hazard of dying. by a low effective renal plasma ﬂow, an elevated ﬁltration
American Journal of Transplantation 2005; 5: 1469–1476 1473
Rocha et al.
fraction and an elevated renal vascular resistance. The au- and lowest in the ARFD group. This likely represents the
thors concluded that renal function impairment character- reaction of physicians to reduce the CsA dose in light of
ized by intense renal vasoconstriction should not be con- worsening renal function rather than a renoprotective ef-
sidered a contraindication for transplantation (8). However, fect of higher CsA levels. Since we did not have data on
the above-mentioned study by Navis et al. does not ad- CsA dose, this hypothesis could not be conﬁrmed. It should
dress perioperative ARF or need for acute dialysis. In our be noted that CsA levels were relatively high in all groups.
study, baseline GFR was also higher in recipients who de- Moreover, trough CsA levels correlate poorly with drug
veloped ARF than in those who did not, but this was due exposure as measured by the area under the curve (25).
to the higher GFR encountered in the ARFnD group, which Therefore, given all the accumulated data on the nephro-
had the highest proportion of CF patients. In contrast, 65% toxicity of CsA, our results should be interpreted with cau-
of patients who developed ARFD had a baseline GFR that tion and do not suggest that CsA is free of renal toxicitiy
was either decreased or consistent with CKD. For each after LTx.
1 mL/min/1.73 m2 increase in baseline GFR, we observed
a 2% reduction in the odds of developing ARFD. Therefore, PD was used by 74% (17/23) of the patients that were dia-
transplant physicians do need to be wary of a low baseline lyzed. PD was used as the sole modality in 13 patients and
GFR when selecting patients for LTx. This is a complex is- as the initial modality in four. In this retrospective analysis,
sue because some patients have hemodynamic-mediated we could not ascertain the factors inﬂuencing the choice of
reductions in GFR that might actually improve after LTx, as dialysis modality but we hypothesize that PD was favored
shown by Navis et al. (8). Therefore, a thorough nephro- due to the following factors. PD is a slow, continuous pro-
logic evaluation should be performed in all candidates that cedure well suited for unstable ICU patients. In addition,
exhibit a decreased baseline GFR to deﬁne the nature of it does not require anticoagulation, a clear advantage for
renal impairment and help judge the potential risk for renal recipients that may still have productive thoracic drains.
complications after LTx. Lastly, this study was performed before CVVHD became
the preferred continuous modality at our institution. Given
Treatment with parenteral amphotericin B increased the that most patients used PD, we could not determine if the
odds of developing ARFD (OR 3.04, CI 1.03–8.98). Ampho- choice of dialysis modality inﬂuenced outcome. Some sug-
tericin B is known to be nephrotoxic, especially when com- gest that PD may provide insufﬁcient solute clearance for
bined with CsA (21). We also observed a potential syner- hypercatabolic patients in the ICU (26). In an open, ran-
gism between amphotericin B and aminoglycoside but the domized comparison of CVVHD and PD in patients with
low number of patients using this combination precluded infection-associated ARF in Vietnam, Phu and coworkers
us from formally addressing this interaction. Transplant found that assignment to PD was associated with a 5.1
physicians must be cautious when using amphotericin B in times higher odds of death and a 4.7 times higher odds of
LT recipients; when acceptable, agents such as voricona- need for future dialysis (27). However, small, uncontrolled
zole (22) and caspofungin (23) should be preferred. studies have shown that PD adequately controls ﬂuid and
metabolic derangements in hypercatabolic patients with
Compared to patients who stayed on MV for ≤1 d, those ARF (28–33). More recently, a prospective, randomized
who remained on MV for >1 d were 6.16 times more likely crossover study of 87 patients with hypercatabolic ARF
to have ARFD. The direction of causality in the association showed that tidal PD achieved the standards of adequacy
between length of MV and ARFD, however, is not com- as per National Kidney Foundation guidelines (34). Over
pletely clear. Although, chronologically, MV precedes renal the last 5 years, our institution as well as many others has
failure by a week this does not imply that it causes ARFD. It shifted to CVVHD as the preferred dialysis modality for
is certainly possible that evolving ARF might impair wean- unstable ICU patients (35). This decision was more likely
ing from MV due to difﬁculties in maintaining adequate inﬂuenced by commodity and ease of use CVVHD than by
ﬂuid balance. Furthermore, in patients undergoing PD, the objective data that CVVHD is superior to PD (36). We be-
presence of large volumes of dialysis ﬂuid in the peritoneal lieve the poor outcome of our ARFD patients resulted from
cavity might compromise respiratory mechanics, or even factors unrelated to the type of dialysis used. This assertion
interfere with proper patient positioning for weaning. An is supported by a recent meta-analysis (37).
alternative possibility is that the association between MV
and ARFD is indirect: for example, critically ill patients are Survival analysis showed a marked increase in early mortal-
at risk for both prolonged MV and ARFD. In this light, pro- ity in the ARFD group. Sixteen of these patients died during
longed MV remains a good predictor of ARFD because the initial hospitalization for LTx, for an in-hospital mortal-
it represents several variables associated with disease ity of 70%. This falls within the reported range of 50–80%
severity. mortality for patients with dialysis requiring ARF in the ICU
(38–41), post-CT surgery (42–45) and after heart transplan-
Since CsA can cause ARF in other settings (9), we hypoth- tation (46,47). In a Cox proportional-hazards model, ARFD
esized that higher CsA trough levels would be associated was strongly associated (HR 6.71) with mortality. However,
with ARF after LTx (24). However, mean CsA levels within we could not ascertain whether ARFD had a direct effect
the ﬁrst week after LTx were highest in the NoARF group on mortality or simply represented a marker for severity
1474 American Journal of Transplantation 2005; 5: 1469–1476
Acute Renal Failure after Lung Transplantation
of disease. Theoretically, adequate dialysis should be able tality is direct or related to disease severity. Finally, the
to control volume status, electrolyte and acid–base dis- inﬂuence of dialysis modality on the outcome of patients
turbances and avoid mortality directly attributable to ARF. who develop ARFD after LTx warrants further investigation.
Nonetheless, it has been shown that dialysis-requiring ARF In the mean time, efforts should be concentrated on reno-
greatly increases mortality in the ICU (48) and following car- protective strategies to avoid ARFD in high-risk patients.
diac surgery (42), even when adjusted for comorbidity and
postoperative complications. It should be noted that cri-
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