SERUM CREATININE MEASUREMENTS IN MEN WITH LOWER URINARY TRACT SYMPTOMS SECONDARY TO BENIGN PROSTATIC HYPERPLASIA

8/9/2019 SERUM CREATININE MEASUREMENTS IN MEN WITH LOWER URINARY TRACT SYMPTOMS SECONDARY TO BENIGN PROSTATIC HYPERPLASIA

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ELSEVIER

SERUM CREATININE MEASUREMENTS IN MEN WITH

LOWER URINARY TRACT SYMPTOMS SECONDARY TO

BENIGN PROSTATIC HYPERPLASIA

GLENN S. GERBER, EVAN R. GOLDFISCHER,

THEODORE G. KARRISON. AND GREGORY T. BALES

ABSTRACT

Objectives. To determine the usefulness of routine serum creatinine measurements in men with lower urinary

tract symptoms secondary to benign prostatic hyperplasia (BPH) and to correlate these findings with patient

age, symptom severity, and comorbid diseases.

Methods.

We analyzed serum creatinine measurements in 246 consecutive men presenting for evaluation

of voiding symptoms and BPH. Multiple logistic regression analysis was used to determine whether the

International Prostate Symptom Score (IPSS), quality-of-life measure from the IPSS, patient age, or a history

of diabetes mellitus or hypertension predicted abnormal creatinine levels.

Results. An elevated serum creatinine level was noted in 1 1 (26 of 245) of evaluable patients. Only a

history of diabetes or hypertension predicted the presence of renal insufficiency. Among men with no history

of comorbid disease, increasing age was significantly associated with the finding of an abnormal creatinine.

Neither the overall symptom score nor the quality-of-life measure was significantly associated with the like-

lihood of detectable renal dysfunction.

Conclusions. Medical renal disease secondary to diabetes or hypertension appears to be the most likely

cause of elevated serum creatinine measurements in men with BPH and renal insufficiency. We were unable

to identify subgroups of patients in whom the risk of renal dysfunction is sufficiently low to avoid routine

serum creatinine measurements.

UROLOGY

49: 697-702, 1997. 0 1997, Elsevier Science Inc. All rights

reserved.

I

t has been estimated that 25 of American men

will require treatment for the relief of lower urinary

tract symptoms secondary to benign prostatic hyper-

plasia (BPH) by the age of 8O.l In addition, many

other patients will present for evaluation of voiding

symptoms without subsequently receiving therapy.

Therefore, it is evident that the initial diagnostic eval-

uation of men with BPH should be performed in an

efficient and cost-effective manner to ensure proper

patient care. It is well known that bladder outlet ob-

struction secondary to BPH can lead to upper urinary

tract changes, hydronephrosis, and renal failure.2,3

For this reason, it has been recommended that all

From the Section of Urology, Department of Surgery, and De-

partments ofHealth Studies and Medicine, University of Chicago

Pritzker Schoo l of Medicine, Chicago, Illinois

Reprint reque sts: Glenn S. Gerber, M.D., University of Chi-

cago, Section of UrologyNC 6038, 5841 South Maryland Ave-

nue, Chicago, IL 60637

Submitted: October 15, 1996, accepted (with revisions): No-

vember 30, 1996

0 1997, ELSEV IER SCIENCE INC.

ALL RIGHTS RESERVED

patients presenting with symptoms of prostatism un-

dergo an assessmentof renal function by the mea-

surement of serum creatinine.’ Although it has been

suggested hat approximately 14 of men with symp-

tomatic BPH have evidence of renal insufficiency, this

is likely to be an overestimation becausemost studies

evaluating the relationship between BPH and renal

function have been performed in patients undergoing

prostatectomy.

4+g In contrast, little information has

been presented regarding renal dysfunction in men

undergoing evaluation of lower urinary tract symp-

toms of varying severity.l’ In the present study, the

results of serum creatinine measurements n 246 con-

secutive men with symptomatic BPH were correlated

with symptom score, age, quality-of-life measures,

and comorbid disease to help define the usefulness

of creatinine determinations in the evaluation and

treatment of such patients.

MATERIAL AND METHODS

Between July 1995 and January 1996,246 consecutive men

(aged 45 years or older) who presented to the urology clini c

0090-4295/97/$17.00

PI1 SOOUO-4295(97)00069-l 697


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TABLE I. Baseline data in 246 consecutive patients presenting for

evaluation of lower urinary tract symptoms secondary to benign

prostatic hyperplasia

History of

No History of

All Patients DM or HTN DM or HTN

(n = 246) (n = 109)

(n = 137)

Age [yr s, mean + SD) 66.0 + 9.8*

67.3 2 9.3 64.9 +- 1 O.O*

Symptom score-IPSS

[mean k SD) 13.4 2 7.9

13.5 f 7.9 13.3 + 8.0

Mild (O-7) 72 (29 ) 28 (26 ) 44 (32 )

Moderate (8- 19) 1 15 (47 ) 57 (52 ) 58 (42 )

Severe (20-35)

59 (24 ) 24 (22 ) 35 (26 )

Qual ity-of-life score (mean t SD) 2.9 + 1.6 3.0 f 1.5 2.8 -e 1.6

DM 35 (14 ) 35 (32 )

-

HTN 87 (35 ) 87 (80 )

-

Serum creatinine (mg/dL)

(mean ? SD)

1.12 + 0.29* 1.17 t 0.33 1.08 k 0.24*

Abnormal serum creatinine

(> 1.4 mg/dL) 26 (1 l )*

17 (16 ) 9 (70/o)*

K E Y .

DM = diabetes mellitus; HTN = hypertension; IPSS = International Prostate Symptom Score.

*Missing

value in I patient.

at the University of Chicago with lower urinary tract symp-

toms secondary to BPH underwent initial e valuation as rec-

ommended by the guidelines panel of the Agency for Health

Care Policy and Research.’ This evaluation included comple-

tion of the International Prostate Symptom Score (IPSS), med-

ical history, physical e xamination, urinalysis, and measure-

ment of serum creatinine. Further testing of patients was at

the discretion of the treating physician. Patients with a history

of chronic renal insufficiency, prostate cancer, or surgical

treatment for BPH, as well as those with co mplete urinary

retention at the time of evaluation, were excluded from this

analysis. The normal range of serum creatinine measurements

was considered to be 0.5 to 1.4 mg/dL. Those patients with

an elevated serum creatinine level underwent further evalu-

ation, including renal ultrasonography, measurement of post-

void residual (PVR) urine volume, or repeat serum creatinine

measurements, at the discretion of the treating physician. The

decision to initiate medica l or surgical therapy for BPH was

made based on patient preference after consultation with the

physician.

Statistic al analysis was performed using multiple logistic

regression to determine the risk (odds ratio) of having an

abnormal serum creatinine level as a function of age, symp-

tom score, quality-of-life score, and the presence of comorbid

disease (diabetes mellitus or hypertension). Parameter esti-

mates were obtained using the method of maximum likeli-

hood, and significan ce levels were based on Wald ’s test.”

P values less than or equal to 0.05 were regarded as statisti-

cally significant. The 95% confidence intervals for the true

odds ratios were also calculated.

RESULTS

Among the 246 consecutive patients presenting

for evaluation of lower urinary tract symptoms

secondary to BPH, 2 had incomplete data (Table

I). Descriptive statistics for all patients are shown

in the first column of Table I. The mean age was

66 years (range 43 to 90). Slightly fewer than one

third of the patients had symptom scores in the

698

mild range (0 to 7), nearly one half had scores in

the moderate range (8 to 19>, and about one quar-

ter had scores in the severe range (20 to 35). The

mean quality of life score from the IPSS was 2.9.

A history of diabetes or hypertension was noted in

14 and 35 of the patients, respectively. The

overall mean serum creatinine measurement was

1.12 mg/dL, and 11 of men (26 of 245) had an

abnormal level at the time of initial evaluation.

Results are also presented separately for men

with and without a history of diabetes or hyper-

tension, because the presence of these common,

chronic comorbid diseases is likely to affect serum

creatinine measurements independently of the ef-

fects of BPH. Men with a history of either of these

diseases were slightly older, but they had similar

symptom and quality-of-life scores. However, the

finding of an elevated serum creatinine was noted

more than twice as often in these men compared

with those without a history of these diseases (16

[17 of 1091 versus 7 [9 of 1361).

Descriptive data regarding serum creatinine lev-

els stratified by symptom score (mild, moderate,

or severe), as well as by the presence or absence

of the comorbid conditions, are presented in Table

II. Consistent differences in creatinine levels and

the percentage of patients with abnormal mea-

surements are again seen between those with a his-

tory of diabetes or hypertension compared with

those with no history of either of these diseases.

However, there is no apparent trend of increasing

creatinine levels with increasing symptom scores.

Based on multiple logistic regression analysis in-

corporating the effects of age, symptom score

(treated as a continuous variable), quality-of-life

UROLOGY 49 (51, 1997


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TABLE

II. Serum creatinine measurements and incidence of

abnormal creatinine levels in patients presenting with symptomatic

BPH stratified by symptom score (IPSS)

Mild Moderate Severe

(IPSS O-7) (IPSS 8-l 9) (IPSS 20-35)

All patients

No. 72 115

58

Mean + SD 1.09 t 0.27 1.15 k 0.32 1.10 + 0.24

No. abnormal 9 (12.5 ) 13 (11.3 ) 4 (6.9 )

History of diabetes or

hypertension

No. 28 57

24

Mean 2 SD 1.14 t 0.32 1.20 2 0.35 1.1 1 2 0.28

No. abnormal

6 (2 1.4 ) 9 (15.8 ) 2 (8.3 )

No history of diabetes

or hypertension

No. 44 58

34

Mean t SD 1.06 t 0.22 1.09 k 0.27

1.09 5 0.20

No. abnormal

3 (6.8 ) 4 (6.9 ) 2 (5.9 )

KEY : IPSS = International Prostate Sympto m Score.

score, and comorbidity (Table III), only a history

of diabetes or hypertension was significantly as-

sociated with the presence o f renal insufficiency

(P = 0.045). After excluding patients with either

or both of these comorbid diseases, increasing age

was significantly associated with the finding of an

elevated creatinine (Table III). However, neither

the overall symptom score nor the quality-of-life

measure significantly predicted the finding of an

elevated creatinine measurement among the entire

group of patients studied or among those without

a history of diabetes or hypertension.

The mean age and symptom score in the 9 pa-

tients with an elevated creatinine measurement

(more than 1.4 mg/dL) and no history of diabetes

or hypertension were 71.4 years and 12.6, respec-

tively. In the 17 patients with an abnormal creat-

inine level and a history of either or both of these

diseases, the mean age and symptom score were

68.0 years and 10.9, respectively. Minimally ele-

vated creatinine measurements (1.5 to 1.6 mg/dL)

were noted in 6 of 9 men (67 ) without comorbid

disease, whereas 2 patients in this group had levels

of 1.7 mg/dL and 1 had a level of 2.4 mg/dL (Fig.

1). Evidence of upper urinary tract dilation or a

significantly increased PVR urine volume (100 cc

or greater) were noted in only 1 of these 9 men.

Among the 17 patients with an abnormal creati-

nine level as well as diabetes or hypertension, 7 of

17 men (41 ) had minimal elevations. The re-

maining 10 patients in this group had creatinine

measurements of 1.7 to 2.4 mg/dL, although only

3 of 17 (18 ) patients had evidence of hydrone-

phrosis or a PVR of greater than 100 cc. Finally,

among men younger than 60 years of age with or

without a history of comorbid disease, an abnor-

UROLOGY 49 (S), 1997

ma1 creatinine measurement was noted in only 1

of 23 (4.3 ) and 1 of 39 (2.6 ) cases, respectively

(Fig. 1).

COMMENT

Voiding dysfunction secondary to BPH signifi-

cantly affects the health and quality of life of many

TABLE III. Effects of patient age, symptom

score, quality-of-life score, and presence

of comorbid disease (diabetes mellitus or

hypertension) on incidence of abnormal serum

creatinine measurement using multiple logistic

regression analysis * in all patients and

in those men with no history of diabetes

mellitus or hypertension

(95

Odds Confidence

Ratio Interval1 P Value

All patients

Age (per decade) 1.56

Symptom score

(per 10 points) 0.46

Quality-of-life score 1.21

Presence of

diabetes or

hypertension 2.42

No history of

diabetes mellitus

or hypertension

Age (per decade) 2.17

Symptom score

(per 10 points) 0.57

Quality-of-life score 1.26

*Univariate analysis gave simila r results.

(0.97, 2.52) 0.067

(0.19, 1.14) 0.092

(0.80, 1.81)

0.363

(1.02, 5.76) 0.045

(1 .Ol, 4.67) 0.046

(0.13, 2.58) 0.469

(0.65, 2.44) 0.497

699


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Quality of Life Score

FIGURE 1. The re/UtionShip be-

tween (A) serum creatinine and

patient age, (B) symptom score,

and(C) qual ity-of-life score in men

with no history of diabetes or hy-

pertension. A single asterisk indi-

cates 1 patient, and the numbers

2 to 9 indicate the number of pa-

tients at each observation point.

Those patients with asterisks

above the horizontal line had ab-

normal serum creatinine levels.

700

UROLOGY 49 61, 1997


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older men. As a result, all aspects of the evaluation

and treatment of patients with lower urinary tract

symptoms warrant careful scrutiny. It has been

well documented that bladder outlet obstruction

by an enlarging prostate can lead to renal insuffi-

ciency. However, the likelihood of this occurrence,

the relationship between symptom severity and

the finding of an elevated serum creatinine mea-

surement, and the impact of age and comorbid dis-

ease on renal function in men with BPH have not

been well studied.3,5,10,12

In the present analysis of 246 consecutive men

presenting for the evaluation of voiding symp-

toms, the incidence of renal dysfunction (serum

creatinine greater than 1.4 mg/dL) was 11 (26 of

245). Among all patients studied, only a history of

diabetes or hypertension significantly predicted

the presence of an elevated creatinine measure-

ment. Minimal abnormalities (serum creatinine of

1.5 to 1.6 mg/dL) were noted in many patients,

and most men with renal insuff iciency had no ev-

idence of upper urinary tract changes or poor blad-

der emptying. Most importantly, symptom sever-

ity and quality-of-life measures correlated poorly

with the presence of elevated creatinine levels and

could not be used to accurately predict the likeli-

hood of renal insufficiency secondary to BPH. It is

possible, however,

that inclusion of men with

more severe symptoms, such as those with com-

plete urinary retention and those undergoing sur-

gery, would have demonstrated a correlation be-

tween increasing symptom severity and renal

dysfunction.

Previous attempts to define the incidence of renal

dysfunction in men with BPH have primarily fo-

cused on patients with complete urinary reten-

tionl2*l3

and those with sufficiently severe symp-

toms to warrant surgical intervention.2*4-g’14 In

these studies, as many as 30 of men had evidence

of renal insufficiency.4 More recently, Koch et al.”

reported that 9.5 of men with lower urinary tract

symptoms of varying severity had an elevated se-

rum creatinine, although this study also included

men with complete urinary retention. These au-

thors noted that only 3 of 32 (9 ) patients with

minimally abnormal creatinine measurements had

evidence of upper tract dilation, whereas 33 (7 of

21) of those men with a more significantly elevated

creatinine level had hydronephrosis of varying de-

grees. Although Koch et al. found no correlation

between symptom severity and the finding of renal

insufficiency, no attempt was made in their study

to investigate the relationship of comorbid disease

and abnormal creatinine measurements. Overall, it

appears that medical renal disease secondary to di-

abetes and hypertension is the most common cause

of renal dysfunction in older men with lower uri-

nary tract symptoms and BPH.

The limited likelihood of significant renal insuffi-

ciency in men presenting for the evaluation of symp-

tomatic BPH might suggest that determination of se-

rum creatinine could be omitted in selected groups

of patients in an effort to contain costs. In addition

to measuring creatinine, many patients with abnor-

malities will require an assessment of PVR urine vol-

ume or radiographic evaluation of the upper urinary

tract, which will further increase costs. Because the

number of men with BPH who annually undergo

evaluation in the United States is very large,l even

limited reduction of testing in such patients could

significantly lower the overall economic impact as-

sociated with the management of voiding symptoms

in older men. However, avoidance of screening for

renal dysfunction even in selected patients with BPH

appears to be unwise for several reasons. First, as

was noted by Koch et al.,lO we found it difficult to

identify subgroups of patients in whom the risk of

renal insufficiency was limited enough to avoid rou-

tine serum creatinine measurement. The lack of cor-

relation of symptom severity and renal dysfunction

is supported by the findings of Mukamel et al.,5 who

also reported on several patients with occult and

progressive renal damage secondary to BPH who had

minimal voiding symptoms. We did find, however,

that significant renal insufficiency was rare in men

younger than 60 years of age, which was also noted

by Mukamel and coworkers. In contrast, Koch et

allo could not identify a significant correlation be-

tween increasing patient age and a greater likelihood

of upper urinary tract dilation.

Other factors that argue against the omission of

screening for renal dysfunction in men with voiding

symptoms and BPH include the economic impact of

renal failure and its deleterious effects on overall

health.15 Irreversible upper urinary tract changes in

patients with prostatic enlargement may occur, and

progressive renal insufficiency leading to the need

for dialysis can be seen, despite relief of bladder out-

let obstruction.3z12 The long-term direct and indirect

costs associated with renal insufficiency and dialysis

are significant, and it is unlikely that the economic

benefit derived from the elimination of routine se-

rum creatinine measurements would outweigh the

costs associated with even the rare patient who de-

veloped chronic renal failure. Therefore, early detec-

tion of renal insufficiency in men with BPH is likely

to be cost-effect ive because it will presumably lead

to the introduction of appropriate therapy and

avoidance of long-term renal damage. Routine mea-

surement of serum creatinine in men with BPH also

serves as a baseline assessment of renal function,

which may be of value in those patients with pro-

gressive voiding dysfunction who return for repeat

evaluation. Finally, determination of serum creati-

nine in patients with symptomatic BPH is appropri-

ate because the potential effectiveness and morbidity

UROLOGY 49 (51, 1997

701


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of therapy are adversely affected by the presence o f

renal insufficiency. Specifically, the use of alpha-l

receptor antagonists, such as terazosin and doxazo-

sin, may be problematic in men with renal dysfunc-

tion because of blood pressure abnormalities or

other factors. In addition, the results of prostatic sur-

gery in men with chronic bladder distension or az-

otemia are often less successful and are more fre-

quently associated with complications than in

patients with normal renal and bladder func-

tion.

12,16,17

CONCLUSIONS

In patients with lower urinary tract symptoms

secondary to BPH presenting for evaluation, a his-

tory of diabetes mellitus or hypertension is signif-

icantly associated with the likelihood of an abnor-

mally elevated serum creatinine measurement.

Among men with no history of these comorbid

diseases, increasing age also predicts a greater

chance of renal insufficiency. Neither symptom

score nor the quality-of-life measure from the IPSS

is associated with serum creatinine levels. In most

patients with BPH and renal dysfunction, medical

renal disease secondary to diabetes or hyperten-

sion is the most likely cause of elevated serum cre-

atinine measurements. Despite the infrequent oc-

currence of azotemia secondary to bladder outlet

obstruction in patients with voiding symptoms

and BPH, it still appears appropriate to measure

serum creatinine routinely to avoid long-term ad-

verse sequelae and improve the likelihood of suc-

cessful treatment outcomes.

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Denton SE, Holtgrewe HL, Lange JL, McClennan BL, Mebust

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UROLOGY 49 (5), 1997

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SERUM CREATININE MEASUREMENTS IN MEN WITH LOWER URINARY TRACT SYMPTOMS SECONDARY TO BENIGN PROSTATIC HYPERPLASIA