2009 THE AUTHORS.

JOURNAL COMPILATION 2009 BJU INTERNATIONAL

Lower Urinary Tract
CHRONIC KIDNEY DISEASE AMONG MEN WITH LUTS DUE TO BPH
HONG

et al.

Chronic kidney disease among men with

lower urinary tract symptoms due to benign
BJUI BJU INTERNATIONAL
prostatic hyperplasia
Sung Kyu Hong, Seung Tae Lee, Sung Jin Jeong, Seok-Soo Byun,
Young Kwon Hong*, Dong Soo Park*, Jae Yup Hong*, Jeong Hwan Son†,
Cheil Kim†, Seok Heun Jang† and Sang Eun Lee
Department of Urology, Seoul National University Bundang Hospital, *Department of Urology, Bundang CHA
Hospital, and †Department of Urology, Bundang Jesaeng Hospital, Seongnam, Korea
Accepted for publication 14 July 2009

filtration rate (eGFR). Univariate and obstruction-related, were significantly

Study Type – Diagnosis (case series)
Level of Evidence 4
OBJECTIVE
To analyse potential association of various
clinical characteristics of benign prostatic
hyperplasia (BPH) with chronic kidney
disease (CKD) among men presenting with
lower urinary tract symptoms (LUTS)
secondary to BPH of varying severity.
PATIENTS AND METHODS
We reviewed the data of 2741 consecutive
patients who presented to our clinic with
LUTS secondary to BPH. For our analysis, CKD
was defined by an elevated serum creatinine
level or decreased estimated glomerular
multivariate logistic regression analyses
were used to address associations of CKD
with various clinical characteristics.
RESULTS
Of the 2741 patients, 161 (5.9%) were
initially classified as having CKD (serum
creatinine ≥133 μmol/L). In multivariate
analysis, peak flow rate (P = 0.001) and a
history of hypertension and/or diabetes
(both P < 0.001) were significantly
associated with CKD, whereas age, body
mass index, prostate-specific antigen level,
prostate volume, postvoid residual, or
International Prostate Symptom Score (IPSS)
were not. When individual symptoms from
the IPSS were analysed, only weak stream
(P = 0.041) and hesitancy (P = 0.048), both
associated with CKD status in age and
comorbidity-adjusted analyses. The results
of secondary analysis with CKD defined as an
eGFR of <60 mL/min/1.73 m2 were similar.
CONCLUSION
Our results show that decreased peak flow
rate and a history of hypertension and/or
diabetes are significantly associated with
CKD in men seeking management for LUTS
from BPH of varying severity.
KEYWORDS
prostate, prostatic hyperplasia, chronic
kidney failure, creatinine

INTRODUCTION
Traditionally, it has been widely assumed
that BOO secondary to BPH can result in
hydronephrosis and even chronic kidney
disease (CKD) [1]. In older men, CKD is an
important medical problem that can even be
life-threatening [2]. It has been reported that
an average of 13.6% of patients presenting to
urological clinics for the treatment of BPH
had renal failure [3]. However, such data
might be regarded as overestimated, as most
of analysed studies involved patients with
relatively severe BPH receiving surgical
management.
In reality, there is currently little information
on CKD in patients with BPH of a wide
spectrum of severity. Although both BPH and
CKD are common disease entities among
ageing men and that can also adversely affect
their quality of life, the relationship between
these medical conditions has not been well
defined so far. Moreover, as can be seen from
available clinical practice guidelines on BPH,
controversy continues on whether to
implement routine screening of serum
creatinine level to identify those with CKD
among men presenting with LUTS secondary
to BPH [4–6]. Thus, we analysed the potential
association of various clinical characteristics
of BPH with CKD among men presenting with
LUTS secondary to BPH of varying severity.
PATIENTS AND METHODS
In this retrospective study, we reviewed data
of men, aged 40–79 years, who presented to
our clinic from May 2006 to April 2008 with
LUTS secondary to BPH. Patients’ medical
records were reviewed to exclude men with
history of prostate cancer, bladder cancer,
prostate surgery of any type, neurogenic
bladder, neurological conditions that can
affect urinary function, and urethral stricture.
Patients who initially visited our clinic
with acutely ill conditions, such as acute
prostatitis, other UTI with fever, complete
urinary retention, and other acute medical
conditions were also excluded. After such
screening, 2741 men were included in the
analysis.
The evaluation of patients included the IPSS,
a medical history, a DRE, urine analysis,
uroflowmetry, abdominal ultrasonography for
measuring postvoid residual urine volume

© 2009 THE AUTHORS

1424 JOURNAL COMPILATION © 2 0 0 9 B J U I N T E R N A T I O N A L | 1 0 5 , 1 4 2 4 – 1 4 2 8 | doi:10.1111/j.1464-410X.2009.08975.x
 CHRONIC KIDNEY DISEASE AMONG MEN WITH LUTS DUE TO BPH

TABLE 1 Characteristics of the patients according to CKD status TABLE 2 The association of various clinical
characteristics in patients with CKD (serum
Mean or n (%) variable No CKD CKD P creatinine level ≥133 μmol/L) assessed by
No. of patients 2580 161 multivariate analysis
Serum creatinine, μmol/L 99.0 169.7
Age, years 64.31 64.14 0.786 Variables Odds ratio P
BMI, kg/m2 24.54 24.44 0.627 Age 0.987 0.270
Serum PSA level >1.4 ng/mL 1361 (52.8) 86 (53.4) 0.351 BMI 0.978 0.495
IPSS >7 2326 (90.4) 147 (93.0) 0.266 Serum PSA level 1.336 0.192
Quality-of-life score >3 1812 (70.2) 112 (69.6) 0.857 IPSS 1.332 0.225
Prostate volume >30 mL 1618 (62.7) 101 (64.0) 0.287 Quality-of-life score 1.290 0.462
Qmax <15 mL/s 1547 (60.0) 117 (72.7) 0.001 Prostate volume 1.521 0.212
PVR >100 mL 97 (3.8) 3 (1.9) 0.213 Qmax 0.529 0.001
DM 181 (7.0) 28 (17.4) <0.001 PVR 1.422 0.154
Hypertension 304 (11.8) 44 (27.3) <0.001 DM 2.731 <0.001
Hypertension 2.692 <0.001

(PVR), TRUS of the prostate, and
measurements of serum PSA and creatinine
levels. For TRUS we used the HDI 5000 system
(Philips Medical Systems, Best, Netherlands)
with an end-firing (150°) ultrasound
(5–9 MHz) probe. Prostate height and width
were measured in the axial plane at the
largest-appearing mid-gland level, and
prostate length was measured in the midline
sagittal plane. Total prostate volume and
transition zone volume measurements were
calculated using the formula of a prolate
ellipsoid (height × width × length × 0.52).
In the current study, CKD was primarily
defined as having a serum creatinine level of
≥133 μmol/L, as previously used by others [7].
In a secondary set of analysis CKD was
defined as having an estimated GFR (eGFR) of
<60 mL/min/1.73 m2, as used previously [7].
The eGFR was calculated using an abbreviated
Modification of Diet in Renal Disease
equation [8]. According to these two
definitions, association of variables such as
age, body mass index (BMI), IPSS, PSA level,
prostate volume, maximum flow rate (Qmax),
and presence of self-reported comorbidities
(diabetes mellitus, DM, and/or hypertension)
with CKD was analysed, respectively. Each
item of the IPSS questionnaire was also
analysed separately.
For the statistical analysis, patients were
stratified by age into four groups of 40–49,
50–59, 60–69 and ≥70 years. In assessing BMI
data, patients were categorized according to
teh classification proposed for BMI of Asian
populations (<18.5, 18.5 to <23, 23 to
<27.5, and ≥27.5 kg/m2) [9]. Variables were
dichotomized as previously done by others [7],
i.e. Qmax as ≥15 vs <15 mL/s, IPSS as 0–7
(none-mild) vs >7 (moderate-severe), PVR as
≤100 vs >100 mL, prostate volume as ≤30 vs
>30 mL, PSA level as ≤1.4 vs >1.4 ng/mL, and
presence or absence of comorbid disease (DM,
hypertension). We used multiple logistic
regression to determine the odds ratio of
having CKD as a function of these clinical
variables assessed in each patient. CIs for
the odds ratio were calculated using the
likelihood ratio method, and Wald’s test was
used to verify the significance of variables
included in logistic regression model. In all
tests, P < 0.05 was regarded as indicating
statistical significance.
RESULTS
The mean (SD, range) age of all 2741 patients
was 64.3 (7.5, 40–79) years, the prostate
volume 41.9 (21.4, 20.1–149.5) mL, the PVR
61.8 (45.9, 10–314) mL, the total IPSS
13.5 (6.4, 3–34) and Qmax 12.3 (5.8, 4.0–
35.5) mL/s. Of all patients, 161 (5.9%) had an
elevated serum creatinine level (≥133 μmol/L)
at the initial evaluation and were classified as
having CKD; 12.6% and 7.6% of all patients
were identified as having hypertension and
DM, respectively. The characteristics of the
patients are listed according to CKD status
defined by serum creatinine level in Table 1;
there were no significant differences in age
and BMI between those with and without
CKD. Also, the two groups had no significant
differences in the proportions having a serum
PSA level of >1.4 ng/mL, moderate or severe
LUTS (IPSS >7), high degree of bother (>3),
enlarged prostate (>30 mL), and large PVR
(>100 mL). Men with CKD had a significantly
higher proportion with a Qmax of <15 mL/s
than those without CKD (72.7% vs 60.0%,
P = 0.001). Such results were replicated when
the variables were analysed as continuous.
The incidence of both hypertension and DM
were also significantly higher among those
with CKD (both P < 0.001).
In multivariate analysis incorporating all
of the variables of clinical characteristics,
a history of hypertension or DM (both
P < 0.001) along with Qmax (P = 0.001) were
also independent predictors of CKD among
men with LUTS secondary to BPH (Table 2).
Other variables, e.g. age, BMI, PSA level, IPSS,
quality-of-life score, prostate volume, and
PVR, were not significantly associated with
elevated serum creatinine level. In a
multivariate analysis only of those without
DM or hypertension (2334 men), only Qmax
(P < 0.001) and PVR (P = 0.045) were
identified as independent predictors of CKD.
However, when analysed only among those
with DM and/or hypertension (407 men), only
Qmax was an independent predictor
(P = 0.040).
The associations of individual symptoms from
the IPSS questionnaire with CKD status were
also analysed among all patients (Table 3);
obstruction-related symptoms, e.g. weak
stream (P = 0.041) and hesitancy (P = 0.048),
were significantly associated with CKD in age-
and comorbidity-adjusted analyses. Irritative
symptoms had no significant associations
with CKD.
In the second set of analysis defining CKD by
the eGFR, 494 (18.0%) of all patients had an
eGFR of <60 mL/min/1.73 m2 and were thus

© 2009 THE AUTHORS

JOURNAL COMPILATION © 2009 BJU INTERNATIONAL 1425
H O N G ET AL.
designated as having CKD. In a multivariate
analysis incorporating all of the variables of
clinical characteristics, only a history of
hypertension or DM (both P < 0.001) and
Qmax (P < 0.001) were again independent
predictors of CKD. The PVR volume was
almost significant in this multivariate analysis
(P = 0.083).
DISCUSSION
In the current retrospective analysis of 2741
men presenting with LUTS due to BPH, the
observed incidences of CKD, as defined by
elevated serum creatinine levels, were similar
to data reported by others [10,11]. However,
a wide range of renal failure rate among
patients with BPH has so far been reported,
which might be due to inconsistent methods
of defining renal dysfunction [12–17]. Among
the present patients with LUTS from BPH, Qmax
and a history of DM and/or hypertension were
independent predictors of the presence of
CKD as defined by serum creatinine level or
eGFR. Although there was no significant
association between overall symptom or
bother score from the IPSS questionnaire with
CKD, individual obstructive symptoms, such
as hesitancy and/or weak stream, as elicited
by the IPSS, were significantly associated with
CKD status in age- and comorbidity-adjusted
analyses.
The present results are similar to those
previously reported by others. In their
relatively study of 246 men with symptomatic
BPH, Gerber et al. [17] reported that neither
the severity of LUTS as assessed by the
IPSS nor the quality-of-life measure was
significantly associated with the likelihood of
detectable renal failure, as found in the
present study. Only a history of DM or
hypertension predicted the presence of renal
insufficiency among their patients. Gerber
et al. did not analyse the significance of other
variables such as flow rate, PSA level or
prostate volume. However, the results of the
present study and those of Gerber et al.
indicate that history of DM or hypertension
might be a significant predictor of elevated
serum creatinine levels among men seeking
management for LUTS secondary to BPH. As
Gerber et al. [17] noted in their study, that
patients included in the present study were
those who visited our clinic for management
should be considered in the interpretation
of our data. However, Rule et al. [7], in a
community-based study of the association
1426
Age- and comorbidity-adjusted
Variables odds ratio
Incomplete emptying 1.111
Intermittency 1.016
Weak stream 1.243
Hesitancy 1.203
Frequency 1.017
Urgency 1.039
Nocturia 1.022
of BPH and CKD in 476 patients aged
40–79 years randomly sampled from registry
used for Olmsted County Study, also defined
CKD as a serum creatinine level of
≥133 μmol/L or eGFR of <60 mL/min/1.73 m2;
as in our study, age, serum PSA level and
prostate volume were not associated with
CKD in their study. However, moderate to
severe LUTS as assessed by the IPSS
questionnaire, and diminished Qmax, were both
significantly associated with the presence of
CKD in that study. In the present study, Qmax
was also a significant predictor of CKD, but
total symptom and bother scores from the
IPSS were not. Moreover, in the study by Rule
et al. [7] only hypertension, but not DM, was
significantly associated with the risk of CKD.
The discrepancies between the presetn study
and that of Rule et al. might reflect the
differences in the patients analysed, as men
with LUTS who seek treatment might be
different from those randomly sampled
from a general community. However,
assessing the data from the two cited
studies and the present study suggests
that both BOO and medical comorbidities
might have a significant relationship
with CKD status among men with LUTS
from BPH.
In several referral-based studies of BPH, there
was no significant association of LUTS
severity, as assessed by the IPSS, with the
presence of CKD [13,17,18]. Also, Ponholzer
et al. [19] reported, from a study of men
participating in health investigation, that
LUTS as assessed by the IPSS was not an
independent risk factor for impaired renal
function. Possible explanations for such
phenomenon might include the fact that
some older men with LUTS might indeed
ignore their symptoms and not try to seek
medical management [12]. Under-reporting
of LUTS among older men has been
recognized [1], but it was reported that absent
LUTS in an older man does not necessarily
JOURNAL COMPILATION
TABLE 3
P Association of scores for
0.211 individual IPSS items and
0.281 CKD (serum creatinine level
0.041 ≥133 μmol/L) status
0.048
0.830
0.558
0.785
exclude BPH with BOO. Botker-Rasmussen
et al. [20] reported from a series of older men
with minimal LUTS that half had urodynamic
evidence of BOO. Considering these factors, it
can be suggested that the exclusion of men
with minimal or no LUTS complaint in most
referral-based BPH studies might have
hindered an accurate assessment of the
relationships between BPH and CKD. However,
the same factors also indicate that the
severity of LUTS as complained of by older
men might not always be a useful surrogate
for the actual degree of BOO or, furthermore,
the status of renal function, as found in our
study. Considering our results, it can be
suggested that Qmax rather than scores elicited
by the IPSS might be more significantly
associated with renal function-related status
among men who seek management for LUTS
due to BPH.
There are few community-based studies of
the potential link between BPH and chronic
renal failure, which might be considered more
useful for an accurate depiction of the
association between these diseases. Hunter
et al. [21] reported, from a survey of 2000
randomly sampled Spanish men who were
aged ≥50 years, that the prevalences of self-
reported renal failure related to a prostate
condition and to other causes were 2.4%
and 9%, respectively. However, it would be
difficult to consider the self-reported
prevalence rate as being objective and reliable
assessment. Meanwhile, although not from
a community-based study, Hill et al. [13]
reported that men presenting for prostate
surgery had a 7.7% prevalence of renal
failure, compared with 3.7% in age-matched
controls. Such data show that renal failure in
men with advanced BPH might not simply be
a result of advancing age, as seen in the
present study. However, most of the patients
reported by Hill et al. could have been those
with severe BPH, as they presented for
surgery.
© 2009 THE AUTHORS
© 2009 BJU INTERNATIONAL

As others have reported, our results also
support the view that BOO due to BPH might
be a risk factor for CKD [7]. Despite variables
such as overall symptom score and PVR not
being associated with CKD status, Qmax was
significantly associated with CKD in the
present study. Considering the present data
on PVR, it might also have been significant
with a different threshold value or design
of study. From previous reports, various
mechanisms have been proposed for renal
failure among men with BPH, including
vesico-ureteric junction (VUJ) obstruction
from bladder remodelling [18]. During chronic
retention, bladder wall thickening can occur
leading to a high bladder pressure. High
intravesical pressure can lead to functional
obstruction at the VUJ, or VUR. Anatomical
obstruction at the VUJ can also occur due
to bladder thickening and scarring. The
improvement in renal function seen after
prostatic surgery in patients with BPH might
also support the idea that BPH and CKD are
significantly associated disease entities [14].
However, the exact nature of such an
association is yet to be fully elucidated.
As our study was not community-based, it
can be suggested that men with minimal or
relatively less LUTS might have been excluded
from our analysis, as noted. However, as our
study incorporated relatively many patients,
we believe that they represent a broad
spectrum of men with BPH seen in the clinical
setting. We only assessed comorbidities of DM
and hypertension, even though CKD often has
multiple causes [2,22,23]. Although such
measures would facilitate comparative
analyses of data with previous studies,
improvement in the methods would be
needed in the future investigations of
relevance.
Our results show that a decreased Qmax, with a
history of hypertension and/or DM, are
significantly associated with CKD in men
seeking management for LUTS from BPH of
varying severity. Although the prevalence
of CKD can be considered relatively low
among men with BPH, the possibility of
CKD should be considered in those who have
a low Qmax, obstructive urinary symptoms,
or have comorbidities such as hypertension
and DM.
CONFLICT OF INTEREST
None declared.
© 2009 THE AUTHORS
JOURNAL COMPILATION © 2009 BJU INTERNATIONAL
CHRONIC KIDNEY DISEASE AMONG MEN WITH LUTS DUE TO BPH
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Correspondence: Sang Eun Lee, Department of
Urology, Seoul National University Bundang
JOURNAL COMPILATION
Hospital, 300, Gumi-dong, Bundang-gu,
Seongnam, Kyunggi-do 463-707, Korea.
e-mail: selee@snubh.org
Abbreviations: BMI, body mass index; DM,
diabetes mellitus; CKD, chronic kidney
disease; eGFR, estimated GFR; PVR, postvoid
residual urine volume; Qmax, maximum urinary
flow rate.
© 2009 THE AUTHORS
© 2009 BJU INTERNATIONAL