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Received for publication: 7.7.09; Accepted in revised form: 31.8.09
Nephrol Dial Transplant (2010) 25: 624–627
doi: 10.1093/ndt/gfp529
Advance Access publication 13 October 2009
Long-term renal function after allogenic haematopoietic stem cell
transplantation in adult patients: a single-centre study
Maxime Touzot1, Caroline Elie2, Jill van Massenhove1, Natacha Maillard3, Agne`s Buzyn3 and
Fadi Fakhouri1
1Department of Nephrology, 2Department of Biostatistics and 3Department of Haematology, Universite´ Paris Descartes, AP-HP,
Necker Hospital, Paris, France
Correspondence and offprint requests to: Fadi Fakhouri; E-mail: f.fakhouri@imperial.ac.uk
Abstract
Background. Reported data regarding chronic kidney dis-
ease (CKD) in haematopoietic stem cells transplantation
(HSCT) recipients are highly discrepant.
Materials and methods. We undertook a retrospective
single-centre study in order to assess the rate, risk factors
and outcome of HSCT-associated CKD in 123 allogeneic
HSCT patients.
Results. Twenty-four months after HSCT, CKD [e.g.
glomerular filtration rate (GFR) estimated using the MDRD
formula <60 ml/min/1.73 m2] was noted in 49 patients
(40%). Age ≥ 45 years, early acute kidney injury and a
baseline GFR < 90 ml/min/1.73 m2 predicted the occur-
rence of CKD at 24 months after HSCT. One hundred and
six patients (45 with and 61 without CKD at 24 months)
were followed up for more than 36 months (range 36–142).
Among the 45 patients with CKD at 24 months after HSCT,
CKD persisted in 30 (67%), 10 patients (22%) showed
a transient improvement in GFR but retained CKD and
10 patients (22%) had a sustained improvement of GFR.
Among 61 patients without CKD at 24 months after HSCT,
3 (5%) developed CKD during the follow-up. Our data in-
dicate that HSCT-related CKD probably includes two sub-
sets: a frequent early-onset CKD, a consequence of ARF
in older patients with pre-existent renal impairment, and a
rare late-onset CKD occurring more than 2 years following
HSCT.
Conclusions. Careful monitoring of renal function is
mandatory in patients undergoing HSCT, especially old pa-
tients with pre-existent renal impairment.
Keywords: chronic kidney diseases; haematopoietic stem cell
transplantation
Introduction
Haematopoietic stem cell transplantation (HSCT) is an es-
tablished and increasingly used treatment for a wild range
of haematological malignancies. Improved supportive care
and transplantation procedures have translated into a dra-
matic improvement of overall survival of patients undergo-
ing HSCT. However, long-term organ damage has emerged
as an increasingly identified cause of morbidity and mor-
tality in patients who have undergone HSCT [1].
In the last decade, chronic kidney disease (CKD) aris-
ing after HSCT has been increasingly reported. However,
published studies have yielded discrepant results with an
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HSCT-related chronic kidney disease 625
incidence of HSCT-related CKD ranging from 4 to 66% of
patients [2–9].
We undertook a retrospective single-centre study in or-
der to assess the rate, risk factors and outcome of HSCT-
associated CKD in long-term (>2 years) survivors of a
cohort of allogeneic HSCT patients.
Patients and methods
This retrospective study was undertaken in the Departments of Nephrology
and Haematology in Hoˆpital Necker, Paris, France. Using a computerized
database, we identified all adult (>18 years) patients who had undergone
an allogeneic HSCT between January 1995 and December 2005. Patients
who had survived more than 2 years after HSCT were included in the
study. Patient’s medical records were reviewed and relevant data collected.
CKD was defined by an estimated glomerular filtration rate
(eGFR) <60 ml/min/1.73 m2 noted on at least two occasions at ±3 months
from the 24-month follow-up time point. GFR was estimated using the
Modification of Diet in Renal Disease (MDRD) study simplified equation
[10].
Acute kidney injury (AKI) occurring within the 100 first days after
HSCT was evaluated according to the RIFLE criteria [11].
Hypertension was defined by a systolic blood pressure >140 mmHg
and/or a diastolic blood pressure >90 mmHg and/or the need for antihy-
pertensive drugs.
Results
The present study included 123 patients. The median
follow-up was 64 months (range 24–159). Fourteen pa-
tients died during the study period, and 7 were lost during
the follow-up.
The patient characteristics at the time of HSCT are shown
in Table 1. All patients received graft-versus-host disease
(GVHD) prophylaxis with methotrexate and cyclosporine
A [target therapeutic through (C0) level between 200 and
450 ng/ml for at least 9 months, then progressively de-
creased and stopped at 12 months in the absence of GVHD].
Forty-five patients (39%) presented an episode of AKI. No
patient required renal replacement therapy.
CKD at 24 months after HSCT
CKD was noted in 49 patients (40%) 24 months after HSCT
(Table 2). Five patients (4%) had a severe renal impairment
(eGFR <30 ml/min/1.72 m2) including one patient requir-
ing dialysis.
In univariate analysis, age ≥ 45 years, a baseline eGFR
<90 ml/min/1.73 m2, AKI following HSCT and fludarabine
use predicted the occurrence of CKD. Multiple myeloma
was more frequently noted in patients with CKD compared
to those without it, but difference did not reach statistical
significance (20% versus 8%, P = 0.052). Gender, TBI,
use of nephrotoxic drug including calcineurin inhibitors
and episodes of GHVD (cutaneous or digestive) were not
associated with CKD. In multivariate analysis, age ≥ 45
years, AKI and a baseline eGFR < 90 ml/min/1.73 m2
predicted the occurrence of CKD at 24 months, with an
odd ratio of 5.91 (2.27–15.43), 4.54 (1.73–11.95) and 2.43
(1.04–5.66), respectively (Table 3).
Table 1. Characteristics of 123 patients who had survived more than 2
years after allogeneic haematopoietic stem cell transplantation (HSCT)
All N = 123
F/M 67/56
Median age (years) (range) 41 (18–69)
<45 years 71 (58%)
≥45 years 52 (42%)
Haemopathy
Acute myeloid leukaemia 33 (27%)
Chronic myeloid leukaemia 28 (23%)
Acute lymphoblastic
leukaemia
19 (15%)
Non hodgkin lymphoma 17 (14%)
Multiple myeloma 16 (13%)
Chronic lymphoblastic
leukaemia
2 (2%)
Others 8 (6%)
Donor
Related 103 (84%)
Unrelated 20 (16%)
Chemotherapy
Cyclophosphamide 97 (79%)
Misulban 18 (15%)
Fludarabine 26 (21%)
Melphalan 7 (6%)
TBI 89 (72%)
Median (SD) SCr at the time
of HSCT (µmol/l)
82 ± 37 (40–441)
Median (SD) GFR at the time
of HSCT (ml/min/1.73 m2)
92 ± 23 (10–152)
AKI 45 (39%)
CKD at 24 months 49 (39%)
30 < GFR < 60
ml/min/1.73 m2
46 (37%)
GFR < 30 ml/min/1.73 m2 5 (4%)
Death 13 (11.3%)
F/M, female/male ratio; TBI, total body irradiation; SCr, serum creatinine;
GFR, glomerular filtration rate estimated using the MDRD simplified
formula. CKD, chronic kidney disease; AKI, acute kidney injury.
GFR evolution during the first 24 months after HSCT
Patients with or without CKD at 24 months experienced a
similar drop in GFR during the first 3 months (−28 ±
23 ml/min/1.73 m2 versus −26 ± 22 ml/min/1.73 m2,
respectively, P = 0.70), with a baseline GFR lower in
the first group than the second (81 ± 23 ml/min/1.73 m2
versus 98 ± 22 ml/min/1.73 m2, P < 0.001 (Figure 1).
At 24 months after HSCT, eGFR had dropped by 36 ±
22 ml/min/1.73 m2 in patients with CKD versus 17 ±
24 ml/min/1.73 m2 in those without CKD (P < 0.001).
Long-term outcome of patients
Follow-up ≥ 3 years. One hundred and six patients, in-
cluding 45 patients with and 61 patients without CKD at 24
months, were followed up for more than 36 months (range
36–142). In all, 43 patients (41%) had CKD more than 3
years after HSCT.
Among 45 patients with CKD at 24 months after HSCT,
30 patients (67%) showed persistent renal impairment with
a median GFR at 46.5 ml/min/1.73 m2 at the last follow-
up (range 24–59). Ten patients (22%) showed a slight and
transient improvement in GFR but retained CKD at the last
follow-up (median GFR at 57 ml/min/1.73 m2). Ten patients
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