1
Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients
with Polycystic Kidney Disease
Gauri Bhutani1*, Brad C. Astor
1, 2, Didier A. Mandelbrot
1, Lori Mankowski-Gettle
4,
Timothy Ziemlewicz4, Shane A. Wells
4, Leah Frater-Rubsam
6, Vanessa Horner
5,6,
Courtney Boyer1, Jennifer Laffin
7, Arjang Djamali
1, 3
1Divsion of Nephrology, University of Wisconsin School of Medicine and Public
Health, Madison, Wisconsin, USA; 2Department of Population Health Sciences,
University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin,
USA; 3Division of Transplant Surgery, University of Wisconsin School of Medicine and
Public Health, Madison, Wisconsin, USA; 4Department of Radiology, University of
Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA;
5Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison,
Wisconsin, USA; 6Wisconsin State Laboratory of Hygiene, University of Wisconsin,
Madison, Wisconsin, USA; 7Department of Pediatrics, University of Wisconsin,
Madison, USA.
Corresponding Author:
Gauri Bhutani, MBBS
University of Wisconsin School of Medicine and Public Health
1685 Highland Avenue, # 5135 MFCB, Madison, WI – 53705
Phone – 608-262-0331; Fax – 608-262-6734
Email - [email protected]
Kidney360 Publish Ahead of Print, published on December 4, 2020 as doi:10.34067/KID.0001182019
Copyright 2020 by American Society of Nephrology.
2
ABSTRACT
Background: Polycystic kidney disease (PKD) accounts for ~15% of kidney transplants
but long-term outcomes in PKD kidney recipients are not well understood.
Methods: In primary kidney recipients at our center (1994-2014), we compared
outcomes of underlying PKD (N=619) to other native diseases (non-PKD, N=4312).
Potential factors influencing outcomes in PKD were evaluated using Cox-proportional
hazards regression and a rigorous multi-variable model.
Results: PKD recipients were older, less likely to be sensitized, or experience delayed
graft function (DGF). Over a median follow up of 5.6 years, 1256 of all recipients
experienced death censored graft failure (DCGF; 115 PKD) and 1617 died (154 PKD).
After adjustment for demographic, dialysis, co-morbid disease, surgical and
immunologic variables, PKD recipients had a lower risk of DCGF (adjusted hazard ratio
[aHR]=0.73; 95% confidence interval [CI]: 0.57-0.93; p=0.01) and death (aHR=0.62;
95% CI: 0.51-0.75; p<0.001). In our multi-adjusted model, calcineurin inhibitor (CNI)
use was associated with lower risk of DCGF (aHR=0.45; 95% CI: 0.26-0.76, p=0.003),
while 5-6 HLA mismatch (aHR=2.1 95% CI: 1.2-3.64, p<0.01), was associated with
higher likelihood of DCGF. Notably, both pre-transplant coronary artery disease (CAD)
and higher BMI were associated with increased risk of death (aHR: 2.5 for CAD [95%
CI:1.69-3.71], p<0.001; aHR: 1.07 per 1 kg/m2 higher BMI [95% CI: 1.04-1.11;
p<0.001), as well as, of DCGF and acute rejection. Nephrectomy at time of transplant
and polycystic liver disease were not associated with DCGF/death. Incidence of post-
transplant diabetes mellitus was similar between PKD and “non-PKD” cohorts.
3
Conclusion: PKD recipients have better long-term graft and patient survival than non-
PKD. Standard practices of CNI use and promoting HLA match are beneficial in PKD
and should continue to be promoted. Further prospective studies investigating the
potential benefits of CNI use and medical/surgical interventions to address coronary
artery disease and the immunologic challenges of obesity are needed.
4
INTRODUCTION
Polycystic kidney diseases (PKD) refers to genetic tubulo-interstitial diseases which
result in the formation of multiple cysts in the renal parenchyma accompanied by
gradual loss of renal function1. Recent annual incidence rates of end-stage renal disease
(ESRD) from PKD in the United States range between 8-9 per million population,
making it the fourth most common cause of ESRD2. Although new disease-modifying
therapies for PKD are being developed3,4
, renal transplantation is the only alternative to
dialysis after reaching ESRD5,6
. While PKD is responsible for 2-3% of annual incident
ESRD in the US, it is the underlying disease for almost 12-14% of the annual renal
transplants performed2,7
.
Despite being a major primary renal disease leading to ESRD and renal transplantation,
many post-transplant outcomes specific to PKD remain unclear. Epidemiologic studies
have reported graft and patient survival in PKD kidney transplant recipients as equal8-15
,
better7,15-17
, as well as worse18
than non-PKD recipients. PKD recipients show better
graft and patient outcomes than non-PKD in unadjusted reports from large transplant
databases7. Specific transplant or PKD-linked factors that influence post-transplant
outcomes in PKD recipients19
are not known as prior epidemiologic studies have not
assessed these factors rigorously8-16,18,19
. There is also no consensus on the timing of
native nephrectomy and the risk of post-transplant diabetes mellitus (PTDM) in PKD
recipients17
. In order to optimize renal transplantation practices, protocols and patient
education in PKD, we analyzed data from our center for a better understanding of post-
renal transplant outcomes and the factors affecting these outcomes in PKD.
5
PATIENTS AND METHODS
The Wisconsin Allograft Recipient Database (WisARD) was initiated in 1984 to collect
information on all solid organ transplants performed at the University of Wisconsin. All
patients who received a primary kidney transplant at the University of Wisconsin
between January 1, 1994, and June 30, 2014, and were at least 18 years of age at the
time of transplantation were eligible for inclusion in this study. Patients had follow-up
through December 31, 2014. The University of Wisconsin Health Sciences Institutional
Review Board approved this study. The clinical and research activities reported are
consistent with the Principles of the Declaration of Istanbul as outlined in the
'Declaration of Istanbul on Organ Trafficking and Transplant Tourism.
We categorized kidney transplant recipients by the cause of ESRD recorded in the database.
Patients with ESRD from cystic kidney disease were classified as “PKD” and the rest were
grouped as “non-PKD”. We further categorized non-PKD as ESRD due to glomerulonephritis,
diabetes mellitus, hypertension or “other”. Information on baseline characteristics, including
demographics, pre-transplant dialysis, donor characteristics, co-morbid diseases,
immunosuppression, immunologic markers (HLA mismatch and cPRA >10%), prior kidney
transplantation and native nephrectomy, and for immediate graft function were obtained from
the transplant database.
6
Post-transplant outcomes of death-censored graft failure (DCGF), death and acute rejection
were compared across the five causes of ESRD (PKD, glomerulonephritis, diabetes mellitus,
hypertension and “other”) by Kaplan-Meier curves and Cox proportional hazards regression
analyses. Acute rejection was defined as biopsy proven acute cellular and/or acute antibody
mediated rejection. The multi-variable Cox-proportional hazards model was adjusted for age,
gender, race, body mass index (BMI), pre-emptive kidney transplant, dialysis prior to
transplant, duration of dialysis, pre-transplant co-morbidities (coronary artery disease,
congestive heart failure and polycystic liver disease), deceased donor, donor age, prior
transplant, induction agent, calcineurin inhibitor (CNI) and mycophenolate use, the degree of
HLA mismatch (0-2, 3-4 and 5-6) and nephrectomy at time of transplant.
Potential prognostic factors for the outcomes of DCGF, death and acute rejection in PKD
patients post-kidney transplant were investigated using Cox-proportional hazards regression
analyses and the multivariable model described above within the PKD cohort. To get a
complete picture of outcomes in PKD recipients, the cause of graft failure and incidence rates
of PTDM and post-transplant native kidney nephrectomy were also evaluated and compared
with non-PKD recipients using the χ² test (for graft failure) and the above multivariable model
and Cox-proportional hazards regression analyses (for PTDM and post-transplant
nephrectomy). All statistical analyses were performed using Stata 13.1 (stata.com).
RESULTS
7
Baseline characteristics (Table 1): Our cohort included 619 patients with polycystic
kidney disease (PKD) and 4312 patients with other native kidney disease (non-PKD).
Baseline demographic, co-morbid disease, donor/dialysis/immunologic characteristics
and immunosuppression utilization are fully detailed in Table 1.
Incidence of Graft Failure, Death, and Acute Rejection (Table 2, Figures 1-3):
Delayed graft function (DGF) was less common in the PKD recipients (15% [91/617] vs
19% [824/4312] in non-PKD; p<0.01). The incidence rate of death censored graft failure
(DCGF) was also lower in PKD (2.72 per 100-person years in PKD recipients and 4.11
per 100-person years in non-PKD recipients [p<0.001]; adjusted hazard ratios (aHR)
0.73 [95% confidence interval [CI]: 0.57-0.93; P=0.01] for PKD vs non-PKD; Figure
1a). The incidence rate of death was lower in the PKD cohort (3.51 per 100-person years
for PKD recipients and 5.55 per 100-person years in non-PKD recipients [p<0.01];
adjusted hazard ratio (aHR) of 0.62 [95% CI: 0.51-0.75; p<0.001] for PKD vs non-PKD;
Figure 2a). The incidence of acute rejection was similar between PKD and non-PKD
recipients (Figure 3a). Detailed comparison of these outcomes in PKD and specific
causes of non-PKD ESRD is shown in Table 2 and Figures 1b, 2b and 3b.
Risk Factors for Graft Failure, Death, and Acute Rejection in PKD (Tables 3-5):
Graft loss in PKD was from acute rejection in 14% (16/114) and chronic rejection in
54% (62/114). The frequency of recurrent primary disease was significantly lower in
PKD recipients (0% [0/114] vs 5% [60/1156], p=0.01; Figure 4). Several factors were
expectedly associated with DCGF in the PKD cohort including deceased donor (aHR:
8
1.62 [95% CI:1.01-2.58]; p=0.045), donor age (aHR: 1.36 per decade [95% CI:1.16-
1.58]; p<0.001) and HLA mismatch (aHR: 2.1 for 5-6 antigen mismatch vs 0-2
mismatch [95% CI:1.20-3.64]; p=0.009) [Table 3].
Interestingly, the use of CNIs was associated with a strong protection from DCGF (aHR: 0.45
[95% CI:0.26-0.76]; p<0.01 for CNI vs no-CNI) and acute rejection (aHR: 0.52 [95% CI: 0.29-
0.92]; p=0.03) in PKD recipients. There was no significant difference between tacrolimus and
cyclosporine for both DCGF and acute rejection rates (Tables 3 and 5). A higher BMI, on the
other hand, was associated with increased DCGF (aHR: 1.04 per 1 kg/m2 higher BMI [95%
CI: 1.01-1.08]; p=0.028; Table 3) and acute rejection in PKD recipients (aHR: 1.04 per 1
kg/m2 higher BMI [95% CI: 1.01-1.08]; p=0.022; Table 5). Moreover, a higher BMI, also
associated with increased likelihood of death in PKD recipients (aHR: 1.07 per 1 kg/m2 higher
BMI [95% CI: 1.04-1.11; p<0.001; Table 4).
Pre-transplant coronary artery disease strongly associated with death as expected (aHR: 2.5
[95% CI:1.69-3.71]; p<0.001). Interestingly, it also associated with increased risk of both
DCGF (aHR: 1.68 [95% CI:1.03-2.76]; p=0.038) and acute rejection (aHR: 2.37 [95% CI:1.47-
3.84]; p<0.001) in the PKD cohort. Recipient age, on the other hand, strongly associated with
death (aHR: 1.8 per decade increase [95% CI:1.46-2.22]; p<0.001) which was expected but a
paradoxical protective effect for DCGF (aHR: 0.76 per decade increase [95% CI:0.6-0.96];
p=0.019) was noted.
9
Additional prognostic factors that associated with death in PKD were donor age (aHR: 1.24
[95% CI:1.09-1.41]; p=0.001) and the use of “other” subgroup of induction
immunosuppression (aHR: 0.46 in comparison to basiliximab sub-group [95% CI:0.22-0.96];
p=0.038). The latter was only a small fraction of patients amongst the PKD cohort (34/619)
and mainly consisted of patients who received OKT-3 (N=31).
Other than as noted above (lack of CNI maintenance, higher BMI and pre-transplant coronary
artery disease), acute rejection also strongly associated with HLA mismatch, lack of
mycophenolate maintenance and female gender in the PKD cohort (Table 5).
It is noteworthy that two PKD-specific factors, native nephrectomy at time of transplant as well
as the presence of polycystic liver disease, were not associated with increased DCGF, death or
acute rejection in our PKD cohort.
Other post-transplant outcomes in PKD: Recipients with underlying PKD underwent
native nephrectomy more often than “non-PKD” cohort at the time of transplant (27% vs
0.9%; p<0.001; Table 1) and in the post-transplant period (18% vs 0.1%; p<0.001). The
incidence rate of nephrectomy post-transplant in PKD recipients was 2.09 per 100
person years (aHR: 4.57 vs “non-PKD” [95% CI:3.09-6.76]; p<0.001; Table 6). The
incidence of post-transplant diabetes mellitus (PTDM) in the PKD cohort (2.86 per 100
person years), on the other hand, was similar to “non-PKD” causes of ESRD (Table 6).
DISCUSSION
10
We present the largest published observational cohort study of patients with PKD
following kidney transplantation. Our findings confirm that kidney transplant recipients
with PKD have better graft and patient survival than non-PKD recipients. Our study also
reveals that that two potentially modifiable variables – 4 or less HLA mismatch and CNI
use, may be protective for graft failure in PKD patients. Recipient age, BMI and pre-
transplant coronary artery disease were associated with death in the PKD cohort and are
also potentially modifiable variables to some extent. Both native nephrectomy at the
time of transplant and prior polycystic liver disease did not predict graft or patient
survival.
Graft survival was better in the PKD cohort mostly due to significantly lower frequency
of recurrent native renal disease in the allograft whereas acute rejection and other causes
of graft failure were similar between the PKD cohort and non-PKD. Recurrent disease is
known to be significant contributor to allograft loss20
and although recurrent native renal
disease may be seen in most non-PKD causes of ESRD, PKD by its genetic
pathophysiology is inherently safe from this.
Higher HLA mismatch (especially 5-6 antigen mismatch) was associated with both
worse allograft survival and higher acute rejection in our PKD recipients. Although the
importance of HLA matching in current era of immunosuppression has been
questioned21
, it continues to be a standard practice at most transplant centers including
ours. Our findings confirm the importance of HLA matching in appropriate donor
selection for PKD recipients. Higher donor age, and deceased donor are well reported
11
risk factors for DCGF post-renal transplantation overall2,22
. The apparent protective
effect of higher recipient age for DCGF seen in our PKD cohort is likely due to
confounding from longer survival in younger recipients as described in other graft
survival reports23,24
. Our findings indicate that recipient-donor age matching and
promoting living donation are important for optimizing graft survival in PKD recipients
as well.
Calcineurin inhibitor-based therapy is still a cornerstone in renal transplantation
although long-term benefits of CNI to long-term allograft survival are questioned25
. CNI
use associated with better allograft survival within our PKD cohort. This is helpful to
know since both PKD and CNI have been individually linked to increased risk of post-
transplant diabetes19
. In addition, mTOR inhibitors may theoretically seem preferable
agents in PKD recipients as these have some efficacy in inhibiting both renal and liver
cyst growth5. CNI use was also associated with less acute rejection within our PKD
cohort (Table 5) which suggests that the observed benefit from CNI use in PKD group
could be from better immunologic performance of CNI. Given the retrospective nature
of our study and selection bias (only ~10% were on non-CNI regimens), conclusions
cannot be made. Prospective studies of CNI use in PKD recipients post-transplantation
are needed to understand the significance of this observation better, especially in the
current era when new agents like belatacept are also available26
.
Our study also shows superior survival of recipients with PKD compared to non-PKD
kidney transplant recipients. Most prior published studies show similar overall patient8-15
12
and graft survival8-14
in PKD versus non-PKD recipients. One study18
shows worse
survival in PKD patient compared to non-PKD. In this study, the PKD cohort was small
(N=80) and age at transplant was significantly higher for PKD patients (vs non-PKD). In
fact, most of these prior reports employ small numbers8,9,11-14,18
, lack of robust
multivariable adjustment8-15,18
and many include patients transplanted in the 1980s-
1990s when the current standard maintenance immunosuppressants were not in use8,9,12-
15. Our findings of better graft and recipient survival in PKD are consistent with large
transplant registry data7 and one larger case-control study
16. PKD patients were also
shown to have better survival rates compared to a demographic and dialysis vintage
matched non-diabetic control population in a retrospective study of hemodialysis
patient17
. It is possible that residual effect from a lower chronic illness burden in PKD
(as shown in Table 1) contributes to this improved survival despite statistical
adjustments.
The association of recipient and donor age with survival was expected and is well
reported in post-kidney transplant population27
. Pre-transplant coronary artery disease
was highly associated with death in PKD recipients which is not surprising since
cardiovascular disease contributes heavily to post-transplant mortality28
. Notably, pre-
transplant coronary artery disease was also associated with worse DCGF and acute
rejection in our PKD cohort. Coronary artery disease has not been linked with DCGF
and rejection previously to our knowledge although post-transplant hypertension29
and
denovo CHF30
have been. In addition, statin use has been linked with improved post-
transplant outcomes although not consistently for graft outcomes31-34
. Our findings
13
suggest that coronary artery disease is an important potentially modifiable risk factor to
improve multiple post-transplant outcomes in PKD.
Other than coronary artery disease, higher BMI was the only other risk factor that
associated with all 3 outcomes of death, DCGF, and acute rejection. A higher BMI is
well reported to associate with these outcomes in post-kidney transplant setting likely
due to influence of increased cardiovascular risk, changes in pharmacokinetics/dynamics
of immunosuppressive medications as well as the inflammatory state linked with
obesity35,36
. Although obesity by itself should not discourage transplantation in PKD or
otherwise, as outcomes on dialysis are likely to be worse than with transplantation37,38
but prospective studies to understand the best interventions to address the cardiovascular
as well immunologic challenges in obesity are needed, as consistent improvements in
BMI are not straightforward or easy to achieve35,36
. In addition, the contribution of the
increased weight of the native kidneys and/or liver to the BMI in PKD recipients in our
study is not known but can be considerable39
, and how this factor contributes to
outcomes certainly needs investigating as well.
Finally, we also found lack of mycophenolate agent and female gender as risk factors for
acute rejection but not for DCGF. Similar findings have also been reported in post-
kidney transplant setting overall40,41
. Further studies of mycophenolate use and role of
gender in PKD recipients are needed to better inform us about the significance of these
findings. The apparently protective effect on rejection and survival with use of “other”
induction agent (OKT-3 mainly), on the other hand, was likely highly subject to
14
selection bias and error due to the small number who received this form of induction
(N=34) and therefore, this is likely not a reliable finding.
Based on our study findings, we recommend that general nephrologists educate their
PKD patients who have moderate-severe chronic kidney disease (stages 3-4) about
excellent post-transplant outcomes to help encourage timely kidney donation by
family/friends. Given the excellent post-transplant outcomes, it may also be worthwhile
for transplant centers to investigate a GFR cut off >20 ml/min/1.73 m2 for deceased
donor listing for high risk PKD (in whom GFR decline can be as high as 5-7
ml/min/year)42
, who are otherwise healthy but do not have potential donors.
The timing of native nephrectomy (at or post-transplantation) did not significantly affect
allograft or survival outcomes in our study. This is consistent with findings in some
other prior smaller reports43-45
and another recent report46
. Pre-transplant nephrectomy is
well established as undesirable due to increased surgical complications and the risk of
losing native renal function19,47
. Nephrectomy at time of transplant, however, is still not
a universally adopted practice due to concern of potential insults to the new allograft, the
benefit of preserving residual renal function and avoidance of unnecessary surgical
procedure if possible47
. These are important considerations; however, our findings do
strongly suggest safety of a simultaneous nephrectomy. An individualized approach to
timing and need for nephrectomy based on patient’s needs, preference, and surgical risk,
would likely be the most optimal clinical practice48
.
15
Some studies11,15,49,50
and meta-analyses51,52
have showed increased risk of PTDM in
PKD recipients, but this has not been a consistent finding53,54
and most of these studies
have small number of PKD patients. Amongst the 2 largest cohorts, however, one study
has minimally increased risk of PTDM with PKD in an unadjusted analysis15
while the
other has none54
. Our findings (from the largest reported post-transplant PKD cohort to
date) show no increase in risk of PTDM in PKD recipients.
Limitations of our study include the observational nature, single center population,
residual confounding due to differences in baseline characteristics which may not have
been completely accounted for by the statistical adjustments made. A potential era effect
due to the long observation period and immortal time bias may affect outcomes in both
PKD/non-PKD groups. There is also likely heterogeneity of the PKD group with regards
to the underlying genetic mutation. Assessment of underlying genetic disease in PKD is
not advocated as a routine clinical practice5. This practice may change in the near future
as disease specific therapies become available. Assessing outcomes based on genotype
may provide novel genotype specific information about post-renal transplantation
outcomes and complications.
In conclusion, renal allograft and patient survival is better in PKD than in other native
kidney diseases post-kidney transplant. Our study confirms that many currently used
standard transplant practices are associated with better post-transplant outcomes in PKD
recipients. A better HLA match, living donor, recipient-donor age matching and
cardiovascular health should continue to be encouraged during pre-transplant
16
evaluations in this group. For maintenance immunosuppression, both CNI and
mycophenolate appear to be associated with better allograft outcomes. Further
prospective studies are needed to better inform about potential benefits of specific
immunosuppressive agents as well as of potential medical/surgical interventions to
address coronary artery disease and the immunologic challenges in obesity in PKD
recipients. Our findings also strongly suggest that native nephrectomy at time of
transplant is safe and the risk of PTDM is not increased in PKD recipients.
17
DISCLOSURES
All authors have nothing to disclose.
FUNDING
None.
ACKNOWLEDGEMENTS
We acknowledge Dana Clark, MA, for her significant editorial assistance.
AUTHOR CONTRIBUTIONS
G Bhutani: Data curation; Formal analysis; Writing - original draft; Writing - review and
editing
B Astor: Data curation; Formal analysis; Methodology; Writing - review and editing
D Mandelbrot: Writing - review and editing
L Mankowski Gettle: Writing - review and editing
T Ziemlewicz: Writing - review and editing
S Wells: Writing - review and editing
L Frater-Rubsam: Writing - review and editing
V Horner: Writing - review and editing
C Boyer: Writing - review and editing
J Laffin: Writing - review and editing
A Djamali: Conceptualization; Methodology; Resources; Supervision; Writing - review
and editing
Each author takes responsibility that this study has been reported honestly, accurately
and transparently; that no important aspects of the study have been omitted. Each author
accepts accountability for the overall work and will ensure that questions pertaining to
the accuracy or integrity of any portion of the work are appropriately investigated and
resolved.
18
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22
TABLES
Table 1: Baseline characteristics of recipients with polycystic kidney disease (PKD) and
other native kidney disease (Non-PKD).
Variable (units) PKD^ Non-PKD^ P-Value
N=619 N=4312
Age (years) 52.9 (9.13) 48.7 (13.4) <0.001
Female (%) 45.7 39.3 0.002
Non-White Race (%) 6.6 17.2 <0.001
BMI (kg/m2) 27.8 (5.04) 27.2 (5.43) <0.001
Any dialysis prior to transplantation (%) 60.1 78.3 <0.001
Dialysis duration (months) 14.1 (24) 22 (27.24) <0.001
Deceased donor (%) 57.5 60.9 0.107
Co-morbid diseases:
- Diabetes
- Hypertension
- Coronary artery disease
- Congestive heart failure
- Polycystic liver disease
0.3
97.5
21.8
7.4
32.1
16.6
97.6
35.2
11.8
0
<0.001
0.88
<0.001
0.001
<0.001
Induction treatment (%)
• Alemtuzumab
• Basiliximab
• Thymoglobulin
• Other
• None
14.1
61.0
17.6
5.5
10.8
16.4
49.2
22.4
8.2
15.9
<0.001
Calcineurin inhibitor maintenance (%)
Tacrolimus
Cyclosporine
No CNI
52.02
38.77
9.21
52.97
37.71
9.32
0.877
Mycophenolate maintenance (%) 93.1 90.1 0.020
HLA MM
0-2
3-4
5-6
23.6
42.3
34.1
28.8
41.0
30.2
0.02
cPRA > 10% (%) 23.3* 30.8* 0.009
23
Prior kidney transplantation (%) 10.0 22.7 <0.001
Native nephrectomy at transplantation (%) 26.8 0.9 <0.001
Donor age (%) 43.3 (14.2) 42.2 (14.8) 0.0372
^All values are expressed in means (+ standard deviation) or in % as noted in the variable
column. *N=296 for PKD and 2088 for non-PKD; Thymoglobulin denotes rabbit
antithymocyte globulin.
24
Table 2: Outcomes in polycystic kidney disease (PKD) and other native kidney disease groups.
Outcomes
Polycystic kidney
disease
(N=619)
Glomerulonephritis
(N=1331)
Diabetes (N=1209) Hypertension
(N=520)
Other (N=1252)
Death censored graft failure
All events=1256
# Events
Incidence Rate (per 100
person-years)
Adjusted Hazard Ratio#
(95% CI)
115
2.72
1.0
Reference
371
2.98*
1.28 (0.98, 1.66)
P=0.065
304
4.27*
1.51 (1.15, 1.98)
P=0.003
143
4.82*
1.47 (1.09, 1.97)
P=0.011
323
3.87*
1.32 (1.02, 1.72)
P=0.038
Death
All events=1617
# Events
Incidence Rate (per 100
person-years)
Adjusted Hazard Ratio#
(95% CI)
154
3.21
1.0
Reference
363
3.74
1.28 (1.02, 1.59)
P=0.029
656
8.68*
2.23 (1.80, 2.76)
P<0.001
199
6.21*
1.50 (1.18, 1.91)
P=0.001
399
4.59*
1.61 (1.29, 1.99)
P<0.001
Acute Rejection
All events=937
# Events
Incidence Rate (per 100
person-years)
Adjusted Hazard Ratio#
(95% CI)
107
2.76
1.0
Reference
274
3.23
1.16 (0.86, 1.54)
P=0.328
189
2.84
0.99 (0.73, 1.35)
P=0.953
106
3.9^
1.29 (0.92, 1.79)
P=0.135
261
3.51^
1.18 (0.88, 1.57)
P=0.272
#The model was adjusted for all variables noted in Methods: age, gender, race, body mass index (BMI), pre-emptive kidney transplant, dialysis
duration, comorbid disease (coronary artery disease, congestive heart failure, polycystic liver disease), deceased donor, prior transplant, induction,
calcineurin inhibitor use, mycophenolate use, HLA mismatch and nephrectomy at time of transplant. *P<0.01 vs PKD, ^P<0.05 vs PKD; CI
denotes confidence intervals.
25
Table 3: Risk factors for death-censored graft failure in recipients with polycystic kidney
disease
Variable Hazard
Ratio
95% CI P value
Age (per decade) 0.76 0.6-0.96 0.019
Female gender 1.22 0.82-1.81 0.329
Non-white Race 1.14 0.51- 2.55 0.756
Body mass index (per 1 kg/m2 higher
BMI)
1.04 1.01- 1.08 0.028
Dialysis prior to transplantation 1.26 0.77-2.06 0.354
Dialysis duration 1.00 0.99-1.01 0.422
Coronary artery disease 1.68 1.03-2.76 0.038
Congestive heart failure 1.3 0.61-2.74 0.499
Polycystic liver disease 1.12 0.72-1.74 0.609
Deceased donor 1.62 1.01-2.58 0.045
Donor age 1.36 1.16-1.58 <0.001
Prior kidney transplantation 1.15 0.58-2.26 0.689
Induction treatment (%)
Basiliximab
Thymoglobulin
Alemtuzumab
Other
None
Reference
0.81
1.12
1.32
0.67
0.46- 1.43
0.66-1.92
0.60-2.90
0.22-2.03
0.472
0.654
0.497
0.481
Calcineurin inhibitor maintenance
agent
Tacrolimus
Cyclosporine
None
Reference
0.69
1.80
0.42-1.11
0.99-3.27
0.124
0.055
Mycophenolate maintenance 1.05 0.49-2.28 0.892
HLA mismatch
0-2
3-4
5-6
Reference
1.32
2.1
0.77-2.27
1.20-3.64
0.313
0.009
Nephrectomy at transplantation 1.00 0.64- 1.54 0.990
26
CI denotes confidence intervals; HLA: human leukocyte antigen; Thymoglobulin: rabbit
antithymocyte globulin.
27
Table 4: Risk factors for death post-kidney transplant in recipients with polycystic
kidney disease
Variable Hazard Ratio 95% CI P value
Age (per decade) 1.80 1.46-2.22 <0.001
Female gender 0.85 0.60-1.21 0.370
Non-White Race 1.54 0.73-3.27 0.261
Body mass index (per 1 kg/m2
higher BMI)
1.07 1.04- 1.11 <0.001
Dialysis prior to transplantation 1.36 0.88-2.12 0.171
Dialysis duration 1.00 1.00-1.01 0.530
Coronary artery disease 2.50 1.69-3.71 <0.001
Congestive heart failure 0.92 0.44-1.94 0.831
Polycystic liver diseasePolycystic
liver disease
1.02 0.66- 1.56 0.942
Deceased donor 1.35 0.89-2.03 0.156
Donor age 1.24 1.09-1.41 0.001
Prior kidney transplantation 1.40 0.78- 2.48 0.255
Induction treatment (%)
Basiliximab
Thymoglobulin
Alemtuzumab
Other
None
Reference
0.80
0.86
0.46
0.41
0.50-1.27
0.49-1.54
0.22-0.96
0.15-1.12
0.342
0.623
0.038
0.084
Calcineurin inhibitor maintenance
Tacrolimus
Cyclosporine
None
Reference
0.83
1.30
0.54-1.27
0.70-2.40
0.392
0.414
Mycophenolate maintenance 0.94 0.46-1.91 0.864
HLA mismatch
0-2 (reference)
3-4
5-6
Reference
1.23
1.10
0.81-1.86
0.69-1.76
0.335
0.693
Nephrectomy at transplantation 0.83 0.54-1.28 0.401
CI denotes confidence intervals; HLA: human leukocyte antigen and Thymoglobulin: rabbit
antithymocyte globulin.
28
Table 5: Risk factors for biopsy-proven acute rejection post-kidney transplant in recipients
with polycystic kidney disease
Variable Hazard Ratio 95% CI P value
Age (per decade) 0.79 0.62-1.01 0.062
Female gender 1.64 1.07-2.50 0.022
Non-White Race 1.26 0.65-2.47 0.493
Body mass index (per 1 kg/m2
higher BMI)
1.04 1.01-1.08 0.022
Dialysis prior to transplantation 1.27 0.7 9- 2.10 0.325
Dialysis duration 1.00 0.99-1.01 0.816
Coronary artery disease 2.37 1.47 -3.84 <0.001
Congestive heart failure 0.74 0.32-1.72 0.482
Polycystic liver disease 1.25 0.79-1.84 0.392
Deceased donor 0.92 0.59-1.44 0.716
Donor age 1.00 0.85-1.16 0.956
Prior kidney transplantation 2.59 1.38-4.87 0.003
Induction treatment (%)
Simulect
Thymoglobulin
Campath
Other
None
Reference
0.82
1.38
0.13
0.64
0.45-1.49
0.81-2.33
0.03-0.62
0.19-2.14
0.501
0.233
0.010
0.464
Calcineurin inhibitor maintenance
Tacrolimus
Cyclosporine
None
Reference
0.86
1.79
0.53-1.37
0.97-3.32
0.518
0.063
Mycophenolate maintenance 0.33 0.14-0.73 0.006
HLA mismatch
0-2
3-4
5-6
Reference
2.30
4.07
1.21-4.37
2.10-7.92
0.011
<0.001
Nephrectomy at transplantation 1.17 0.74-1.84 0.493
CI denotes confidence intervals; HLA: human leukocyte antigen and Thymoglobulin: rabbit
antithymocyte globulin.
29
Table 6: Incidence of post-transplant events in PKD vs non-PKD
PKD Diabetes Hypertension Glomerulonephritis Other
Post-transplant diabetes
# Events
Incidence Rate (per
100 person-years)
Adjusted Hazard
Ratio# (95% CI; p-
value)
103
2.86
1.0 (Reference)
NA
110
4.55
1.12 (0.82, 1.54)
P=0.480
187
2.27
0.82 (0.62, 1.10)
P=0.187
186
2.54
0.94 (0.7, 1.25)
P=0.656
Post-transplant nephrectomy
# Events
Incidence Rate (per
100 person-years)
Adjusted Hazard
Ratio# (95% CI; p-
value)
59
2.09
1.0 (Reference)
20
0.28
0.14 (0.08, 0.25)
P<0.001
11
0.38
0.22 (0.11, 0.43)
P<0.001
31
0.34
0.18 (0.11, 0.29)
P<0.001
48
0.61
0.33 (0.21, 0.51)
P<0.001
#The model was adjusted for all variables noted in Methods: age, gender, race, body mass index (BMI), pre-emptive kidney transplant,
dialysis duration, comorbid disease (coronary artery disease, congestive heart failure, polycystic liver disease), deceased donor, prior
transplant, induction, calcineurin inhibitor use, mycophenolate use, HLA mismatch and nephrectomy at time of transplant. CI denotes
confidence intervals
Patient and Graft Survival in PKD
30
FIGURE LEGENDS
Figure 1: Death censored graft failure in PKD and non-PKD kidney transplant
recipients.
(a) PKD vs all non-PKD (N=619 [black solid line] and 4312 [black small dashed line],
respectively; p<0.001); (b) PKD (N=619) vs glomerulonephritis (N=1331; grey long dashed
line; p<0.01), diabetes (N=1209; light grey solid line; p<0.01), hypertension (N=520; grey
dotted line; p<0.01) and other (N=1252; black small dashed line; p<0.01) causes of ESRD. The
model was adjusted for all variables noted in Methods: age, gender, race, body mass index
(BMI), pre-emptive kidney transplant, dialysis duration, comorbid disease (coronary artery
disease, congestive heart failure, polycystic liver disease), deceased donor, prior transplant,
induction, calcineurin inhibitor use, mycophenolate use, HLA mismatch and nephrectomy at
time of transplant.
Figure 2: Death in PKD and non-PKD kidney transplant recipients.
(a) PKD vs all non-PKD (N=619 [black solid line] and 4312 [black small dashed line],
respectively; p<0.001); (b) PKD (N=619) vs glomerulonephritis (N=1331; grey long dashed
line; p=NS), diabetes (N=1209; light grey solid line; p<0.01), hypertension (N=520; grey
dotted line; p<0.01) and other (N=1252; black small dashed line; p<0.01) causes of ESRD. The
model was adjusted for all variables noted in Methods: age, gender, race, body mass index
(BMI), pre-emptive kidney transplant, dialysis duration, comorbid disease (coronary artery
disease, congestive heart failure, polycystic liver disease), deceased donor, prior transplant,
induction, calcineurin inhibitor use, mycophenolate use, HLA mismatch and nephrectomy at
time of transplant. *NS denotes not significant
Figure 3: Acute rejection in PKD and non-PKD kidney transplant recipients.
(a) PKD vs all non-PKD (N=619 [black solid line] and 4312 [black small dashed line],
respectively; P=NS); (b) PKD (N=619) vs glomerulonephritis (N=1331; grey long dashed line;
p=NS), diabetes (N=1209; light grey solid line; p=NS), hypertension (N=520; grey dotted line;
p<0.05) and other (N=1252; black small dashed line; p<0.05) causes of ESRD. The model was
adjusted for all variables noted in Methods: age, gender, race, body mass index (BMI), pre-
emptive kidney transplant, dialysis duration, comorbid disease (coronary artery disease,
congestive heart failure, polycystic liver disease), deceased donor, prior transplant, induction,
calcineurin inhibitor use, mycophenolate use, HLA mismatch and nephrectomy at time of
transplant. *NS denotes not significant
Figure 4 (a) Causes of graft loss in PKD cohort. (b) Causes of graft loss in “non-PKD” cohort.
*There was significantly lower frequency of recurrent native renal disease in the allograft in
PKD recipients (p=0.01) whereas acute rejection and other causes of graft failure were similar
between the PKD cohort and non-PKD (N = 114 for PKD and 1156 for non-PKD).
Figure 1a
Figure 1b
Figure 2a
Figure 2b
Figure 3a
Figure 3b
Figure 4a
Figure 4b