Acta Nephrologica 25(1): 17-21, 2011 17

Original Article

Tuberculosis Peritonitis in Patients on

Peritoneal Dialysis: Experience in a
Medical Center
Chien-Hua Chiu 1, 2, Chih-Hsiung Lee 1, 2, Te-Chuan Chen 1, Jin-Bor Chen 1, Chien-Te Lee 1,
Yu-Che Tsai 1, Kuo-Tai Hsu 1, Ben-Chung Cheng 1, Yu-Shu Chien 1, Yu-Jen Su 1,
Shang-Chih Liao 1, and Feng-Rong Chuang 1

1
Division of Nephrology and 2General Medicine, Department of Internal Medicine
Chang Gung Memorial Hospital-Kaohsiung Medical Center
Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China

Abstract

BACKGROUND. Owing to their compromised local immune system, patients with end-stage
renal disease (ESRD), especially those undergoing peritoneal dialysis (PD), are prone to developing
tuberculosis peritonitis (TBP). TBP is an uncommon complication, but the mortality rate is high in PD
patients.
METHODS. We retrospectively reviewed all the cases of TBP occurring in patients receiving PD
at our institution over the past 19 years. Seven cases were identified to have TBP during the study period.
We presented the clinical and diagnostic features of these patients.
RESULTS. The calculated crude rate of TBP patients was 1.0%. The time between onset of
symptoms and diagnosis of TBP was around two weeks. All patients presented with fever and abdominal
pain. Three patients had co-existing extraperitoneal TB. Six patients had positive results of TB culture.
The new TB polymerase chain reaction (PCR) method was applied to four patients who were diagnosed
early by a positive peritoneal fluid TB PCR on an average of 6.5 days. All TBP patients received anti-
tuberculosis therapy. Two patients suffered from side effects of rifampin, such as jaundice and gas-
trointestinal upset. Only one patient died from septic shock. Four patients were switched to hemodialysis.
No recurrence of TBP was observed during a mean follow-up of 32.6 months.
CONCLUSION. Our experience suggests that an effective molecular diagnostic tool (TB PCR)
offers better outcomes for patients with TBP, including early diagnoses, prompt therapy, and decreased
mortality. (Acta Nephrologica 2011; 25: 17-21)

KEY WORDS: tuberculosis peritonitis, peritoneal dialysis, tuberculosis polymerase chain reaction

Introduction dominantly extrapulmonary in dialysis patients, occur-

ring soon after the initiation of renal replacement
Chronic kidney disease is associated with in- therapy (1, 5). Patients with ESRD, especially those
creased susceptibility to bacterial infection due to a undergoing peritoneal dialysis (PD), are prone to de-
decrease in cellular immunity, with other contributing veloping TB peritonitis (TBP) (1, 6). Previous inves-
factors being malnutrition, vitamin D deficiency, and tigations on characteristics of TBP in PD patients
hyperparathyroidism (1-4). Previous data have found were rare in western countries (1, 7-10), but there are
increase in incidence of tuberculosis (TB) in patients a few equivalent studies in Taiwan (11-13). TBP is
with end-stage renal disease (ESRD) compared with curable with proper diagnosis and treatment. The aim
that in those with normal renal function. TB is pre- of this study is to describe the clinical and diagnostic
Corresponding author: Dr. Feng-Rong Chuang, Division of Nephrology, Chang Gung Memorial Hospital, 123 Ta Pei Rd, Niao Sung District,
Kaohsiung 833, Taiwan, R.O.C. Tel: +886-7-7317123 ext. 8306, Fax: +886-7-7322402, E-mail: tony-770430@yahoo.com.tw
Received: April 29, 2010; Accepted: July 26, 2010.
18 Chiu, Lee, Chen, Chen, Lee, Tsai, Hsu, Cheng, Chien, Su, Liao and Chuang

Table 1. Demographic characteristics in 7 PD patients with TBP

Patient No. 1 2 3 4 5 6 7
Gender/Age (years) F/71 F/62 M/71 M/52 F/66 F/55 F/61
Underlying renal disease DM CGN CGN CGN CGN CGN CGN
Duration of CAPD (months) 48 48 3 96 48 12 48
Kt/V 2.3 2.13 1.29 2.7 1.82 1.67 2.18
Duration between S/S and diagnosis of TBP (days) 23 20 30 8 5 6 7
Signs/symptoms
Fever + + + + + + +
Abdominal pain + + + + + + +
Body weight loss + +
Diarrhea +
Turbid dialysate + + + + +
Peritoneal fluid WBC
Count/mm3 580 313 763 130 1234 160 205
Cell type NP NP LP NP NP NP NP
Chest X-ray N N I* I** N PE N
Extraperitoneal TB No No P P No A No
TBP patients 1 to 4 were diagnosed from 1990-2004 and patients 5 to 7 from 2005-2009.
Abbreviations: PD, peritoneal dialysis; TBP, tuberculosis peritonitis; F, female; M, male; DM, diabetes mellitus;
CGN, chronic glomerulonephritis; S/S, signs/symptoms; NP: neutrophil predominance; LP: lymphocyte predominance;
N: normal; I*, infiltrations of bilateral upper lobes; I**, infiltrations of bilateral lower lobes; PE, pleural effusions;
P, pulmonary TB; A, TB arthritis.

features of TBP among the patients undergoing PD in designed for rapid purification of pathogen DNA from
a single medical center. whole blood, body fluid, or solid tissue.

Methods Results

We retrospectively reviewed all the cases of
TBP from a database of 678 PD patients during the
period of January 1, 1990 to December 31, 2009. The
underlying renal disease, duration of dialysis, Kt/V,
clinical presentations, biochemistry with microbiology
records, peritoneal fluid WBC counts and differential
counts, diagnostic methods, side effects of anti-
tuberculosis drugs, treatment results, and patient
outcomes were analyzed. All data were presented as
mean SD.
A definitive diagnosis of TBP was established
by a positive peritoneal fluid TB culture or a finding
of caseating granulomata in a peritoneal biopsy. TBP
was also highly suspected with a positive TB PCR or
a TB smear with the atypical presentations of PD
peritonitis. The old method of TB PCR used phenol-
chloroform extraction, a liquid-liquid extraction tech-
nique (equal volumes of a phenol: chloroform mixture
and an aqueous sample mixed, forming a biphasic
mixture). This method was used in molecular biology
for isolating DNA, RNA, and protein before 2004.
After 2004, a new method using DNA extraction kit
assays (The QIAamp DNA Mini Kit and QIAamp
DNA Blood Mini Kit, Qiagen, Hilden, Germany) was
Seven cases were identified to have TBP during
the study period. The calculated crude rate of TBP
patients was 1.0% (7 of 678). Two were men and five
were women. Clinical characteristics, diagnostic
methods and outcomes for these TBP patients are
illustrated in Tables 1 and 2. The mean age for the
patients at diagnosis was 62.5 7.3 years. The duration
of PD prior to the onset of TBP was 43.2 30.1 months.
The duration between onset of symptoms and diagnosis
of TBP was 14.1 5.3 days. The average of Kt/V was
2.01 0.4. The underlying etiologies for ESRD were
chronic primary glomerulonephritis (85.7%, 6/7) and
diabetes mellitus (14.3%, 1/7). Laboratory studies
revealed mean serum calcium (10.4 0.8 mg/dL, range
from 9.6 to 12.1), mean serum albumin (3.0 1.0
g/dL, range from 1.4 to 4.4), and mean intact-parathyroid
hormone (446.8 333.5 pg/mL, range from 111 to
1092). The average of days of fever subsided after
treatment was 5.1 4.9 days and that of clearness of
dialysate after therapy was 6.0 1.9 days.
All TBP patients presented with fever (100%, 7/
7) and abdominal pain (100%, 7/7). There were also
associated turbid dialysate (71.4%, 5/7), weight loss
(28.5%, 2/7), and diarrhea (14.2%, 1/7). Peritoneal
 Tuberculosis Peritonitis in Peritoneal Dialysis Patients
Table 2. Diagnostic methods and clinical outcomes of 7 PD patients with TBP
Patient No.
Diagnostic methods: Peritoneal fluid
TB PCR
TB smear
TB culture
Associated with bacterial peritonitis
Antibiotic administered
Fever subsided after therapy (days)
Clearness of dialysate after therapy (days)
Switched to hemodialysis
Patient outcomes
Abbreviations: ND, not done; Y, yes; D, died; S, survived.
*intraperitoneal antibiotic administered for bacterial peritonitis.
**intravenous antibiotic administered for pneumonia.
fluid WBC counts ranged from 130 to 1,236/mm3 and
the differential counts were neutrophil predominant
(85.8%, 6/7). Chest X-rays of three patients (42.8%,
3/7) revealed bilateral upper and lower lobes infiltra-
tion or pleural effusion. The diagnoses of TBP were
made from the positive results of TB cultures (100%,
6/6), TB-PCR (80%, 4/5), or positive TB smears
(14.2%, 1/7) in the peritoneal fluid. Extraperitoneal
TB was diagnosed as pulmonary TB (28.5%, 2/7) and
TB arthritis (14.2%, 1/7). Only patient 1 had con-
comitant bacterial peritonitis and received intraperi-
toneal antibiotic therapy. Intravenous antibiotic was
administered in patient 3 due to an associated pneumo-
nia.
All TBP patients received anti-tuberculosis
therapy. The treatment protocol was administered
using a combination of isoniazid (200-300 mg/day),
rifampicin (450-600 mg/day), pyrazinamide (750-
1000 mg/day) and ethambutol (400 mg/day), plus
pyridoxine (50 mg/day) for a total 6-12 months. Pyrazi-
namide and ethambutol were stopped after 0.5-3 months.
Six of the seven patients were successfully cured. Two
of our patients (28.5%) suffered from the side effects
of rifampin, such as jaundice and gastrointestinal upset.
Only patient 3 died of septic shock related to
TBP, complicated by pneumonia at day 21 of hospitali-
zation. Four patients were switched to hemodialysis
due to TBP. No recurrence of TBP was observed dur-
ing a mean follow-up of 32.6 months (range from 6 to
120 months) after completion of therapy.
Discussion
TB is a devastating global health problem, and
there is an increased risk (6.9- to 52.5-fold) of TB in
patients with ESRD compared with the general popula-
tion (14, 15). In our study, the calculated crude rate
19
1 2 3 4 5 6 7
ND ND + + + +
+
+ + + + ND + +
+
+* +**
5 3 17 3 4 2 2
8 6 9 4 6 6 3
Y Y Y Y No No No
S S D S S S S
of TBP was lower (1%) than that reported earlier (10).
None of these patients had previously received a renal
transplantation or immunosuppressant therapy. We
attribute this lower calculated crude rate of TBP to
decrease in direct contamination via the use of twin-
bag exchange systems. These twinbag exchange sys-
tems offer the maximum protection against peri-
tonitis during PD 16 and have been used in our unit
since 1996. A significant difference (30.3 vs. 48.8
patient-months/episode of peritonitis, P = 0.021, by
Wilcoxon rank sum test) in peritonitis rates was detected
between the patients with twin-bag exchange and Y-
set systems in our unit. We observed that the peritonitis
rate decreased including TBP after the switch to twin-
bag exchange system. However, the data were limited
due to fewer patients before 1996 and lower diagnostic
rate of TBP before 2004.
The average interval between onset of symptoms
and diagnosis of TBP in recent studies by Talwani and
Horvath was around six weeks, and 3 weeks by Hung
et al. in Taiwan (7, 9, 13). In our study, the interval
was around two weeks. This discrepancy might be
related to the early application of the new diagnostic
TB PCR kits. TB PCR detection is an important mo-
lecular diagnostic technique for species-specific and
early diagnosis of TBP, but the sensitivity rate (43-
77%) varies among different target organisms (17,
18). Nevertheless, conflicting results were noted on
whether TB PCR should be a routine application or
not (19, 20). In our study, four (80%, 4/5) patients
were diagnosed early by positive peritoneal fluid TB
PCR on an average of 6.5 days with prompt treatment
given. TB PCR detection was not routinely used in
our PD program prior to January 2002 because of the
low sensitivity rate (13.4%). TBP was diagnosed by
positive TB culture and/or acid-fast stains from peri-
toneal fluid or by caseating granulomata in a peritoneal
20 Chiu, Lee, Chen, Chen, Lee, Tsai, Hsu, Cheng, Chien, Su, Liao and Chuang
biopsy (12). In 2004, our molecular laboratory method
switched to the new assay of TB PCR, which targets
the 123 base pair of TB insertion sequence IS6110.
The sensitivity rate of TB PCR from 2,319 cases in
our hospital was 81.64% from 2002 to 2009 and the
specificity rate of TB PCR was 96.85% in the same
period. Positive predictive rate was 76.28% while
negative predictive rate was 97.70%. False negative
rate was 18.35% while false positive rate was 3.15%.
Peritoneal fluid TB PCR would be examined when
patients undergoing PD presented with prolonged
symptoms despite of empiric antibiotic treatment,
recurrent peritonitis, or negative bacterial cultures.
Therefore, we emphasize that TB PCR plays a crucial
role in the early rapid diagnosis of TBP and can
notably improve the outcomes of the patients.
Furthermore, the extraperitoneal TB rate was
about 8-28% in Turkey and 15.4-20% in Taiwan (9,
12, 13, 21). Lungs were the most common site of the
extraperitoneal lesions. Pleura, fallopian tube, lymph
node, spleen, or joint lesions were also reported in
previous studies (7, 9, 12, 21). In our study, three (3/
7, 42.8%) patients had extraperitoneal TB. Two pa-
tients had pulmonary TB, and one patient had TBP
with TB arthritis. Pulmonary TB was common in our
TBP patients. We suggest that concomitant extra-
peritoneal TB in PD patients should be highly sus-
pected upon diagnosis of TBP.
As for the treatment of TBP, no consensus has
been established, and the ISPD 2005 guideline sum-
marized concisely the principles of therapy for TBP
patients. Four drugs were recommended, namely
rifampin, isoniazid, pyrazinamide, and ofloxacin.
However, this treatment protocol was established
from the experience of treating extrapulmonary tuber-
culosis in end-stage renal disease (9, 22). Data from
other studies on anti-tuberculosis treatment outlined
regimens including at least three drugs, namely rifamp-
in, isoniazid, and pyrazinamide (19, 23). According
to previous data, adverse reactions to antituberculosis
drugs were mainly pyrazinamide-induced hepato-
toxicity, with risk factors such as age (> 60 years) or
previous history of hepatitis (23-25). Lui SL reported
rifampicin-induced liver function impairment and
thrombocytopenia, and isoniazid-induced confusion
in Chinese PD patients complicated with TB (8). In
our study, a combined therapy using four drugs includ-
ing rifampin, isoniazid, pyrazinamide and ethambutol
was given, with ethambutol replacing ofloxacin.
Ethambutol and pyrazinamide were administered for
no more than 3 months with no obvious side effects
observed. In addition, we also tapered the dosage of
pyrazinamide and ethambutol in adjustment to renal
function. The dosage of pyrazinamide was reduced
by half to 0.75-1 g/day as compared with that of about
1.5-2 g/day 8, 9 in other studies, while the dosage of
ethambutol was 400 mg/day. Two (28.5%) of our
TBP patients suffered from side effects of rifampicin.
Patient 6 developed gastrointestinal upset related to
rifampicin after one-month treatment. The symptoms
improved after rifampicin was withdrawn. Patient 7
suffered from rifampicin-induced jaundice after the
treatment for 2 weeks. The jaundice disappeared
after rifampicin was stopped. We believe that TB
treatments can be individualized with different
dosages. The side effects of anti-tuberculosis agents
should be kept in mind and carefully monitored, es-
pecially with rifampin or pyrazinamide.
According to the 2000 ISPD guideline, TBP was
an indication for removing the catheter (26), but the
2005 ISPD guideline concerning TBP mentioned that
removal of the catheter is still a contentious issue
(22). Current data also support that primary removal
of the Tenckhoff catheter is not indicated in TBP in
either the western countries or in Asia (1, 8, 9). In our
study, the four patients having TBP between 1990 and
2003 had their catheters removed and were switched
to hemodialysis following the 2000 ISPD guidelines,
while the other three patients who developed TBP after
2005 continued PD following the 2005 ISPD guidelines.
TBP is an uncommon complication with mor-
tality rates ranging from 15-30% in PD patients (13,
27-30). The best known variable contributing to death
due to TBP is delayed treatment (7, 9, 10). In general,
patients whose treatment was delayed 4 weeks from
the onset of symptoms ultimately died of TBP (13).
In our study, the mortality rate for our TBP patients
was around 14.3% and lower. The major reasons were
early diagnosis and prompt treatment. Our average
time lag between onset of symptoms and diagnosis
was around two weeks, mostly attributable to the use
of TB PCR. Only patient 3 died of TBP, complicated
by pneumonia and septic shock, due to a delayed
diagnosis. The duration between onset of symptoms
and treatment was 30 days, and the diagnosis of TBP
was derived via a positive culture for TB.
In conclusion, TBP is an infrequent disease with
a high mortality rate in PD patients. Delayed diagnosis
or treatment will influence the outcome and mortality
of patients. Our experience suggests that an effective
diagnostic tool such as the TB PCR test can provide
an alternative choice for early TBP diagnosis, resulting
in prompt therapy, better patient outcome, and de-
creased morbidity and mortality.
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