Endourology and Stones

Predictive Value of Leukocytosis for

Infectious Complications After
Percutaneous Nephrolithotomy
Ibrahim Halil Bozkurt, Ozgu Aydogdu, Tarik Yonguc, Omer Koras, Volkan Sen,
Serkan Yarimoglu, and Tansu Degirmenci
OBJECTIVE To investigate the natural history of white blood cell (WBC) values and incidence of leukocytosis
after percutaneous nephrolithotomy (PCNL), factors associated with development of post-
operative leukocytosis, and predictive value of WBC count for infection.
METHODS A total of 303 patients who underwent PCNL for renal stones were included in the recent study.
Electronic medical records of the patients were reviewed retrospectively to collect daily serum
leukocyte counts and perioperative cultures. WBC count was followed daily for patients with
positive urine culture and/or postoperative fever until leukocyte levels turned to normal limits.
RESULTS Leukocytosis was detected in 133 of the 303 patients (43.9%). The mean preoperative and
postoperative WBC counts were 7.73
2.01  106 cells/mL and 11.9
3.31  106 cells/mL,
respectively. The average postoperative WBC count increased by 4.2
2.99  106 cells/mL over
the rst 2 postoperative days. Receiver operating characteristic curve analysis resulted in an area
under the curve of 0.87 and 0.80 for postoperative WBC count and absolute WBC count dif-
ference, respectively. The thresholds provided by the analysis were 14.05  106 cells/mL and an
increase greater than 5.25  106 cells/mL, respectively.
CONCLUSION Our data show postoperative leukocytosis is common after PCNL and represents a normal
physiologic response to surgery. Our study demonstrated that 14.05  103  106 cells/mL WBC
count and absolute difference in WBC count from baseline of 5.25  103  106 cells/mL were
signicantly associated with post-PCNL sepsis development. Further studies are needed to
determine the signicance of leukocytosis for infectious complications after PCNL. UROLOGY
86: 25e29, 2015.
2015 Elsevier Inc.

P
ostoperative infection is a potentially devastating
complication after percutaneous nephrolithotomy
(PCNL). In several studies examining the out-
comes of PCNL, sepsis was detected as a leading periop-
erative cause of death.1,2 Thus, it is important to diagnose
the infection as early as possible after PCNL. But in the
early postoperative period, clinicians usually nd
nonspecic indicators of infection. Although leukocytosis
may be a sign of developing infection in the early post-
operative period, it may also be part of normal surgical
response.3 In the early postoperative period, patients
frequently have an elevated white blood cell (WBC)
count. Elevations in postoperative WBC values may
trigger an expensive and unguided workup in search of an
early infection.
Financial Disclosure: The authors declare that they have no relevant nancial interests.
From the Department of Urology, Izmir Bozyaka Training and Research Hospital,
Izmir, Turkey
Address correspondence to: Ibrahim Halil Bozkurt, M.D., F.E.B.U., Department of
Urology, Izmir Bozyaka Training and Research Hospital, Saim Cikrikci, Street No. 59,
Bozyaka, Izmir, Turkey 35170. E-mail: ihalilbozkurt@yahoo.com
Submitted: February 18, 2015, accepted (with revisions): April 23, 2015
We aimed to investigate the natural history of WBC
values and incidence of leukocytosis after PCNL, factors
associated with development of postoperative leukocy-
tosis, and predictive value of WBC count for infection.
METHODS
A total of 303 patients who underwent PCNL for renal stones
were included in the recent study. Electronic medical records of
the patients were reviewed retrospectively to collect daily serum
leukocyte counts and perioperative cultures. A detailed history,
including past renal surgery, nephrostomy insertion, and recur-
rent urinary tract infection, was obtained from all patients.
Preoperative laboratory investigations included urine analysis,
midstream urine culture, complete blood count, and renal
function tests. The stones were evaluated with low-dose
computed tomography and/or excretory urography preopera-
tively. If the culture was negative, the patient was given a single
dose of prophylactic intravenous broad-spectrum antibiotic at
anesthesia induction and continued until the time of neph-
rostomy removal. Patients who had positive cultures
(>100.000 cfu/mL) were treated with appropriate antibiotics
based on sensitivity prole for at least 7 days. The PCNL pro-
cedure was postponed until a negative culture was obtained after

2015 Elsevier Inc. http://dx.doi.org/10.1016/j.urology.2015.04.026 25

All Rights Reserved 0090-4295/15

Figure 1. Mean leukocyte counts at the operation day and
postoperative follow-up period.
appropriate antibiotic therapy in the patients with positive urine
cultures. Furthermore, antibiotic prophylaxis of these patients
was given according to this sensitivity prole. The stone burden
was calculated by multiplying the longest diameter by the
perpendicular diameter of the stone, and in cases of multiple
stones, the total stone burden was calculated as the sum of the
burden of each stone.
Operation Technique
All PCNL cases were performed by 2 surgeons (I.H.B. and
T.D.). After induction of general anesthesia, an open-end 6F
ureteral catheter was placed using a cystoscope in the lithotomy
position. The patient was then turned to the prone position.
Percutaneous access was performed using an 18-gauge needle
under uoroscopic guidance, and after successful access, pelvic
urine sample was aspirated and sent for culture (renal pelvic
urine culture). In case of purulent urine coming on the initial
access, an indwelling nephrostomy tube was inserted, and the
operation was postponed to another session after appropriate
antibiotic treatment. After that, a guidewire was inserted into
the collecting system and the tract was dilated using Amplatz
dilators until a 30F Amplatz sheath can be placed. Nephroscopy
was conducted under low pressure and stones were disintegrated
using pneumatic lithotripsy. The stone fragments were removed
with forceps. A sample of extracted stones was rinsed in 0.9%
normal saline, crushed, and sent in a sterile tube with small
amount of 0.9% normal saline for bacterial culture (stone cul-
ture). A 14F nephrostomy tube was placed at the end of each
procedure.
A complete blood count, which includes WBC count, was
obtained from all patients for 2 days after operation routinely.
All patients with negative urine cultures and who did not
experience postoperative fever and/or complications including
prolonged urine leakage and hemorrhage were discharged at the
postoperative second day. Leukocytosis was dened as a WBC
count >12.0  106 cells/mL.4 WBC count was followed daily for
patients with positive urine culture and/or postoperative fever
until leukocyte levels turned to normal limits. All patients were
followed-up postoperatively for systemic inammatory response
syndrome (SIRS) criteria (leukocyte count <4000 or >12,000;
fever >38 C or <36 C; heart rate >90 per minute; respiratory
rate >20 per minute) and blood cultures were provided as
indicated.4 SIRS was diagnosed in patients who met 2 or more
criteria. Sepsis is dened as the presence of a source of infection
together with SIRS.4 Statistical analyses were performed with
26
SPSS 21.0 (Chicago, IL) software package. The independent
sample t test, chi-square test, and Fischer exact test were used for
statistical comparisons. Statistical signicance was set at a
P value of <.05. In patients with sepsis, a receiver operating
characteristic curve was performed to detect the optimal
threshold for maximum single-test postoperative WBC count
and absolute difference in WBC count from baseline. The
thresholds were developed with an equal emphasis on sensitivity
and specicity with the use of the Youden index. The area under
curve was used to quantify the effectiveness of WBC count in
diagnosing sepsis.
RESULTS
Leukocytosis was detected in 133 of the 303 patients
(43.9%). The mean preoperative and postoperative WBC
counts were 7.73
2.01  106 cells/mL and 11.9

3.31  106 cells/mL, respectively. Struvite stones were
detected in 14 of the patients (4.6%). The mean preop-
erative WBC value was 8.9
1.68  106 cells/mL in
these patients. The average postoperative WBC count
increased by 4.2
2.99  106 cells/mL over the rst 2
postoperative days. After reaching peak, the WBC value
declined to a level slightly higher than preoperative level
(Fig. 1). WBC counts were available for all patients on
postoperative days 1 and 2, for 232 patients on post-
operative day 3, and for 102 patients on postoperative 4.
Table 1 summarizes demographic characteristics of the
patients and correlation of risk factors with SIRS ac-
cording to the development of leukocytosis. Patients who
developed postoperative leukocytosis had signicantly
higher mean preoperative WBC value (8.71 vs 6.96 
106 cells/mL; P <.001). Gender, age, recurrent urinary
tract infection, positive preoperative bladder urine cul-
ture, stone culture, and pelvis urine culture were not
associated with postoperative leukocytosis development.
In addition, stone size, multiple access, and operation
time were not found to be predictors of postoperative
leukocytosis.
Eighty-three of the patients (27.4%) met the SIRS
criteria. Table 2 summarizes preoperative, postoperative,
and D leukocyte counts in patients with and without
SIRS. Preoperative bladder urine culture was positive in
33 patients (10.9%), who were treated with culture-
specic antibiotics before surgery. Renal pelvic urine
culture and stone culture were positive in 22 (7.3%) and
37 (12.2%) of the patients, respectively. Sepsis was
detected in 23 of the patients (7.6%).
Receiver operating characteristic curve analysis resul-
ted in an area under curve of 0.87 and 0.80 for post-
operative WBC count and absolute WBC count
difference, respectively. The thresholds provided by the
analysis were 14.05  106 cells/mL and an increase greater
than 5.25  106 cells/mL, respectively (Fig. 2).
COMMENT
Leukocytosis and fever are 2 nonspecic indicators of
infection and may also represent part of a normal physi-
ological response to surgery. It is well documented in the
UROLOGY 86 (1), 2015
Table 1. Demographic characteristics of patients and correlation of risk factors with SIRS
Characteristic Leukocytosis () Leukocytosis () P Value (95% CI)
Age (y), mean
SD 45.3
11.2 47.3
13.4 .249*
Body mass index, mean
SD 27.2
4.8 26.9
5.1 .750*
Stone burden, mean
SD 631.0
384.7 592.9
388.4 .487*
Operation time, mean
SD 122.9
36.8 116.3
40.9 .240*
Fluoroscopy time, mean
SD 98.1
63.3 95.2
66.1 .752*
Preoperative leukocyte count 8.71
1.87 6.96
1.77 <.001*
Gender (male/female), n 94/39 116/54 .647y
Hydronephrosis, n 94 122 .889y
Previous ipsilateral surgery, n 55 66 .486z
Preoperative nephrostomy, n 11 10 .643y
Recurrent UTI, n 35 53 .424y
Access no 2, n 37 23 .054y
Blood transfusion, n 12 18 .700y
Residual stone, n 39 73 .445y
Infection stone, n 9 5 .186z
Positive preoperative UC, n 14 19 .753y
Positive RPUC, n 9 13 .742y
Positive SC, n 16 21 .995y
Preoperative ESWL, n 28 30 .444y
CI, condence interval; ESWL, extracorporeal shock wave lithotripsy; RPUC, renal pelvic urine culture; SC, stone culture; SD, standard
deviation; SIRS, systemic inammatory response syndrome; UC, urine culture; UTI, urinary tract infection.
Leukocytosis: white blood cell count 12,000.
Bold indicates signicant P values.
* Independent sample t test.
y
Chi-square.
z
Fischer exact test.

Table 2. Comparison of preoperative, postoperative, and emerged from the consensus conference by the American
D leukocyte counts in patients with and without SIRS College of Chest Physicians and the Society of Critical
SIRS (), SIRS (), P Value Care Medicine.4 The application of these criteria in the
Count mean
SD mean
SD (95% CI) postsurgical patients should be questioned because the
Preoperative 7.55
1.83 7.79
2.07 .444* surgery itself may induce fever and/or leukocytosis as a
leukocyte normal physiological response to surgery. The expecta-
Postoperative 13.17
3.73 11.43
3.03 .001* tion from a denition that would be used is to differen-
leukocyte tiate the pathologic host response, that the infection may
D leukocyte 5.62
3.57 3.64
2.56 <.001* have a role in, from the normal host response. Our aim
CI, condence interval; SD, standard deviation; SIRS, systemic was to investigate the natural course of WBC counts after
inammatory response syndrome. PCNL and to nd out the variables related to leukocytosis
D Leukocyte postoperative leukocyte  preoperative
leukocyte. to increase the anticipation value in the recent study.
* Independent sample t test. Russo et al8 reported that evaluation of surgical patients
with fever and leukocytosis for an infection source often
literature that stress induces demargination of the white results in unnecessary laboratory and radiographic tests.
cell pool, and the operative trauma alone may be the They proposed to use a standardized practice guideline to
cause of leukocytosis in the patients postoperatively.5,6 signicantly reduce the workup time to treatment and cost.
Draga et al reported that transient post-PCNL fever Erb et al9 reported that leukocytosis was common after
(which accounts for 65% of all fevers) was frequently bowel resection, and leukocytosis was not necessarily sug-
caused by a bodily reaction to the operation and resorp- gestive of postoperative complication. Cohen et al inves-
tion of hematoma and therefore does not entirely predict tigated postoperative leukocytosis in patients undergoing
for post-PCNL sepsis and SIRS. The authors proposed spinal surgery, thoracoscopic surgery, laparoscopic gastric
that fever after postoperative day 1 may be of bacterial surgery, pancreaticoduodenectomy, and cranial surgery.10
origin.7 Postoperative leukocytosis is well studied in or- They reported that leukocytosis was a common nding
thopedic surgery,3 but to our knowledge, no study has yet on postoperative day 1 after a variety of surgical procedures
been undertaken that specically evaluated the incidence and usually resolved by postoperative day 3. They also
of leukocytosis, natural history of WBC counts, and their concluded that leukocytosis was unrelated to clinically
correlation with infectious complications after PCNL. relevant postoperative infectious complications, to the
Although in the past fever was the end point in the invasiveness of the surgery, or to the use of anesthesia.
articles that studied the post-PCNL infectious complica- Goel et al11 investigated leukocytosis after gynecologic
tions, in the recent years, it was suggested to use SIRS robotic surgery in 204 cases. They detected leukocytosis
criteria in urology studies.7 SIRS and sepsis denitions (>11,000) in 29% of the patients in postoperative period.

UROLOGY 86 (1), 2015 27

Figure 2. (A) Receiver operating characteristic curve for postoperative white blood cell (WBC) count. (B) Receiver operating
characteristic curve for absolute WBC count difference. (Color version available online.)
Authors did not nd any correlation between post-
operative leukocytosis and operative time, body mass
index, performance of lymphadenectomy, or length of
hospitalization. Furthermore, no correlation was detected
between postoperative day 1 leukocytosis with fever and
other infectious complications.
It is previously reported by several authors that stone
size, operative time, positive stone culture, positive pelvic
urine culture, and multiple punctures are associated with
post-PCNL infectious complications.12-16 In a recent
study, leukocytosis was not found to be associated with
any of these predisposing factors.
Deirmengian et al3 reported that older age, female
gender, higher modied Charlson comorbidity index and
higher preoperative WBC values were risk factors for
postoperative leukocytosis at total hip and knee arthro-
plasty. In a recent study, only preoperative WBC values
correlated with the likelihood of developing post-
operative leukocytosis. Therefore, factors leading to an
increase in preoperative WBC values were expected to
indirectly affect the likelihood of developing a post-
operative leukocytosis.
Our data show postoperative leukocytosis is common
after PCNL and represents a normal physiologic response
to surgery. In our opinion, elevation from baseline rather
than the absolute WBC count would provide a better
predictor for sepsis after PCNL as nearly half of patients
experience a WBC elevation. The WBC count tends to
make a peak on postoperative day 1, with a subsequent
decline toward normal levels. In 43.9% of the cases,
WBC values increased beyond the level that was dened
as leukocytosis during hospitalization.
28
Our study has some limitations. We aimed to analyze
the WBC values from postoperative period to post-
operative day 4 but not all patients hospitalized for
4 days. Thus, some data were missing for postoperative
days 3 and 4. The preoperative prophylaxis of the pa-
tients who had positive preoperative urine culture was
made with the same antibiotic previously reported on
sensitivity prole as the others had a standard prophy-
lactic antibiotic. As this is a retrospective study, we have
not enough data about the medications that had been
used by patients, which can cause nonspecic
leukocytosis.
CONCLUSION
Our data show postoperative leukocytosis is common after
PCNL and represents a normal physiologic response to
surgery. Our study demonstrated that 14.05  103  106
cells/mL WBC count and absolute difference in WBC
count from baseline of 5.25  103  106 cells/mL were
signicantly associated with post-PCNL sepsis develop-
ment. Further studies are needed to determine the sig-
nicance of leukocytosis for infectious complications after
PCNL.
References
1. De la Rosette J, Assimos D, Desai M, et al; CROES PCNL Study
Group. The Clinical Research Ofce of the Endourological Society
Percutaneous Nephrolithotomy Global Study: indications, compli-
cations and outcomes in 5803 patients. J Endourol. 2011;25:11-17.
2. OKeeffe NK, Mortimer AJ, Sambrook PA, Rao PN. Severe sepsis
following percutaneous or endoscopic procedures for urinary tract
stones. Br J Urol. 1993;72:277-283.
UROLOGY 86 (1), 2015
3. Deirmengian GK, Zmistowski B, Jacovides C, et al. Leukocytosis is
common after total hip and knee arthroplasty. Clin Orthop Relat Res.
2011;469:3031-3036.
4. Levy MM, Fink MP, Marshall JC, et al; SCCM/ESICM/ACCP/
ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Denitions Conference. Crit Care Med. 2003;31:1250-
1256.
5. Kuhlwein EC, Irwin MR, Ziegler MG, et al. Propranolol affects
stress-induced leukocytosis and cellular adhesion molecule expres-
sion. Eur J Appl Physiol. 2001;86:135-141.
6. Landmann RM, Muller FB, Perini C, et al. Changes of immuno-
regulatory cells induced by psychological and physical stress: rela-
tionship to plasma catecholamines. Clin Exp Immunol. 1984;58:
127-135.
7. Draga RO, Kok ET, Sorel MR, et al. Percutaneous neph-
rolithotomy: factors associated with fever after the rst postoperative
day and systemic inammatory response syndrome. J Endourol. 2009;
23:921-927.
8. Russo PR, Landon M, Burkard JF, et al. Fever evaluation cost and
time to treatment in the general surgery patient can be reduced by
using a fever practice guideline. Mil Med. 2014;179:1166-1170.
9. Erb L, Hyman NH, Osler T. Abnormal vital signs are common after
bowel resection and do not predict anastomotic leak. J Am Coll
Surg. 2014;218:1195-1199.
UROLOGY 86 (1), 2015
10. Cohen B, Dery E, Cattan A, Matot I. Is leukocytosis a common
nding in the postoperative period? American Society of Anes-
thesiologists. A3067.
11. Goel M, Muntz HG, McGonigle KF. Leukocytosis after robotic
surgery: commonly observed but clinically insignicant. J Minim
Invasive Gynecol. 2010;17:S34; Abstract 111.
12. Chen L, Xu QQ, Li JX, et al. Systemic inammatory response
syndrome after percutaneous nephrolithotomy: an assessment of risk
factors. Int J Urol. 2008;15:1025-1028.
13. Dogan HS, Guliyev F, Cetinkaya YS, et al. Importance of micro-
biological evaluation in management of infectious complications
following percutaneous nephrolithotomy. Int Urol Nephrol. 2007;39:
737-742.
14. Mariappan P, Smith G, Bariol SV, et al. Stone and pelvic urine
culture and sensitivity are better than bladder urine as predictors of
urosepsis following percutaneous nephrolithotomy: a prospective
clinical study. J Urol. 2005;173:1610-1614.
15. Gonen M, Turan H, Ozturk B, et al. Factors affecting fever
following percutaneous nephrolithotomy: a prospective clinical
study. J Endourol. 2008;22:2135-2138.
16. Korets R, Graversen JA, Kates M, et al. Post-percutaneous neph-
rolithotomy systemic inammatory response: a prospective analysis
of preoperative urine, renal pelvic urine and stone cultures. J Urol.
2011;186:1899-1903.
29