BATO, BATO SA LANGIT:

ANG TINAMAAN NAGKA-TB

A Case Report

In partial fulfillment of the requirements for

Family and Community Medicine IV: TB-DOTS Center

Submitted by:

Acma, Kathleen Ann L.

Agustin, Dan Oliver M.
Bautista, Sheena Christy S.
Calingin, Joshua Dale M.
Fuentevilla, Ness Dareen N.
Gapate, Harlykenn C.
Macabalang, Nezreen U.
Robenta, Kenneth Jed M.
Salac, Lady Lyssah D.

June 21, 2019

1
 TABLE OF CONTENTS

History 4

Physical Examination 8

Primary Impression 10

Salient Features 10

Differential Diagnosis 11

Pertinent Diagnostics 12

Baseline Diagnostics 12

Treatment Plan 13

Case Discussion 15

References 20

2
 OBJECTIVES

1. To discuss a newly diagnosed case of pulmonary tuberculosis in context with

chronic kidney disease.

2. To discuss a case of a Bacteriologically-confirmed Pulmonary Tuberculosis

patient to include:
a. Epidemiology
b. Clinical Presentation
c. Diagnosis
d. Management and Treatment of TB and Chronic Kidney Disease
e. Monitoring
f. Prognosis

3
 HISTORY

I. General Data

This is a case of RN, a known diabetic and chronic kidney disease patient, 58
years old, male, married, Roman Catholic, presently residing in Calaanan, Canitoan,
Cagayan de Oro City. The patient was referred by a private physician from Northern
Mindanao Medical Center on June 7, 2019 for GeneXpert Tuberculosis test.
The patient was the source of information with 90% reliability.

II. Chief Complaint

Chronic productive cough.

III. History of Present Illness

11 months prior to consultation, the patient experienced productive cough with

whitish sputum associated with undocumented fever and dyspnea which prompted
consultation at Madonna and Child Hospital. A chest X-ray was requested and showed
radiological findings suggestive of Pulmonary Tuberculosis. He was immediately treated
with Category 1 anti-TB regimen modified for patients with chronic kidney disease, with
Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol (HRZE) taken three times a week
and Isoniazid and Rifampicin (HR) taken four times a week, alternately.
On the same month, he was bound to Korea via Cebu City for his routine medical
evaluation for his Chronic Kidney Disease. While in Cebu City, he sought second
opinion consultation at Chong Hua Hospital where a chest X-ray was requested
showing similar results. He was advised to continue his anti-TB treatment. However, he
claimed to experience fever with chills which he attributed to his Tuberculosis
medications. Hence, he decided to stop taking his medications after less than a month
of treatment. During his medical evaluation at INHA International Medical Center in
Korea, a Direct Sputum Smear Microscopy Test was requested which showed a
negative result and therefore no additional treatment was done. He continued to have
intermittent episodes of productive cough with whitish sputum and associated dyspnea.
2 months prior to consultation, he once again had his routine medical evaluation
for his Chronic Kidney Disease in Korea. He was admitted for one week with a
diagnosis of Acute Kidney Injury due to severe diet restriction. During the course of his
admission, his chest X-ray had suggestive findings of Pulmonary Tuberculosis. He was
advised for CT scan for immediate clarification but he opted to do the CT scan in the
Philippines.
2 weeks prior to consultation, his CT scan result showed findings suggestive of
Pulmonary Tuberculosis. Upon consultation with a private physician in Northern
Mindanao Medical Center, it was revealed that he continued to have intermittent
episodes of productive cough with whitish sputum, dyspnea, and he had a total weight

4
loss of 16 kg in a span of 1 year. He was then referred to this institution for GeneXpert
test.
On the day of consultation, his GeneXpert test result revealed “MTB detected,
low- Rifampicin resistance not detected.” He was then subsequently enrolled for
treatment.

IV. Past Medical History

In 2009, he underwent through Percutaneous Nephrolithotomy procedure to

remove staghorn calculi on his left kidney.
In 2010, he was diagnosed with Chronic Kidney Disease and has been receiving
treatment in Korea. He visits Korea every 6 months for his routine follow-up medical
evaluations and has the following maintenance medications: Ketoanalogue, Febuxostat,
and Sodium Bicarbonate.
In 2018, he was diagnosed with Diabetes Mellitus Type 2 with Peripheral
Neuropathy and Hypertension. He takes Linagliptin for his diabetes and Amlodipine and
carvedilol for his hypertension. Other maintenance medications include Suboxone
(Buprenorphine), Iberet Folic (Multivitamins + Iron), Pizotifen, and Vitamin B-complex.
Dosage and frequency of intake of the maintenance medications were unrecalled.
The patient has no history of blood transfusion and no known food and drug
allergies.

V. Family History

The patient has no family history of hypertension, diabetes, thyroid problems,

asthma, cancer, and kidney disease. His father died of murder while mother passed
away due to old age.

VI. Personal and Social History

The patient is a high school graduate. He is currently unemployed, but he was a

former reseller of cars. He is a non-smoker, non-alcoholic beverage drinker and non-
illicit drug user. He had a total of 5 sexual partners, all females. He has no history of
contracting sexually transmitted infections.

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 REVIEW OF SYSTEMS

General Mouth Peripheral

(-) night sweats (-) toothache Vascular
(-) malaise (-) sore throat (-) leg cramps
(-) anorexia (-) bleeding gums (-) past clots
(-) bleeding
Skin Throat manifestations
(-) sores (-) hoarseness of voice
(+) pruritus (-) thyroid condition Genitourinary
(-) dryness (-) neck pain (-) polyuria
(-) stiffness (-) nocturia
(-) urgency
HEENT Respiratory (-) dysuria
Head (-) chest pain (-) hematuria
(-) headache (-) hemoptysis (-) infections
(-) dizziness (-) wheezing (-) flank pain
(-) alopecia (-) incontinence
Cardiovascular (-) hesitancy
Eye (-) orthopnea
(-) visual difficulties (-) easy fatigability Musculoskeletal
(-) blurring of vision (-) fainting spells (-) muscle or
(-) double vision (-) palpitations joint pain
(-) flashing lights (-) chest pain/discomfort (-) stiffness
(-) edema; bipedal (-) arthritis
Ear (-) gout
(-) hearing difficulties Gastrointestinal (-) backache
(-) tinnitus (-) dysphagia (-) swelling
(-) vertigo (-) rectal bleeding (-) redness
(-) pain in ear (-) pain upon defecation (-) stiffness in joints
(-) aural discharges (-) hemorrhoids (-) weakness or
(-) belching limitation of
Nose (-) flatulence motion/activity
(-) nasal discharges (-) change in bowel (-) any history of
(-) epistaxis movements trauma
(-) pain in nasal area (-) neck pain
(-) low back pain

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Psychiatric
(-) nervousness
(-) mood, including depression
(-) memory change
(-) suicide attempt

Neurologic
(-) changes in attention, or speech
(-) changes in orientation, memory, insight or judgement
(-) fainting
(-) blackout
(-) weakness, paralysis, numbness or loss of separation
(-) tingling, or “pins and needles”
(-) tremors or other involuntary movements

Hematologic
(-) easy bruising or bleeding
(-) previous history of transfusions

Endocrine
(-) heat or cold intolerance
(-) excessive sweating
(-) excessive thirst
(-) excessive hunger
(-) sleeping problems
(-) polyuria

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 PHYSICAL EXAMINATION

General Survey
The patient was examined conscious, coherent, ambulatory, and not in
respiratory distress.

Vital Signs
Blood Pressure: 120/80 mmHg Weight: 85 kg
Heart Rate: 72 bpm Height: 170 cm
Respiratory Rate: 20 cpm BMI: 29.4 (Obese Class 1)
Temperature: 36.1 degrees Celsius
O2 Sat: 98%

SKIN
The patient has brown skin tone with no lesions noted, warm to touch, moist, with
good skin turgor. A BCG vaccination scar was noted.

HEENT
Eyes: Anicteric sclerae, pink palpebral conjunctiva. Pupils were equally reactive
to light and accommodation.
Ears: No discharges. Weber test no lateralization. Rinne’s test; air conduction
greater than bone conduction bilaterally.
Nose: Nasal mucosa pink, no sinus tenderness.
Throat: Oral mucosa pink, good dentition, with no pharyngeal lesions. Tonsils not
inflamed.
Neck: Trachea midline, neck supple, with no thyroid enlargement. No
lymphadenopathy.

Chest and Lungs

Thorax was symmetric with good chest expansion. Both lungs were resonant,
with clear breath sounds.

Cardiovascular System
Adynamic precordium, distinct heart sounds, regular rate and rhythm, without
murmurs.

Abdomen
Abdomen was flat with normoactive bowel sounds. It was soft and nontender,
with no palpable masses or hepatosplenomegaly.

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Genitourinary System
No discharges, non-erythematous, with no costovertebral tenderness.

Musculoskeletal System
Full range of motion in all joints of the upper and lower extremities. No signs of
swelling, deformities, or weakness.

Nervous System
Mental Status: Alert, relaxed, and cooperative, oriented to person, place, and
time.
Cranial Nerves: CN I - intact olfaction
CN II - good visual acuity
CN III, IV, VI - intact extraocular movement
CN V - able to masticate, intact facial sensory
CN VII - able to smile, able to raise eyebrows, intact corneal
reflex
CN VIII - good sense of balance, BC > AC on the right
CN IX, X - able to swallow, intact gag reflex
CN XI - able to raise shoulders
CN XII - able to protrude tongue
Cerebellum: Normal gait.
Motor: Good muscle bulk and tone, strength 5/5 throughout.
Sensory: Intact.
Reflexes: 2+ and symmetric with plantar reflex down going.

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 PRIMARY IMPRESSION

Bacteriologically-confirmed Pulmonary Tuberculosis, New case, Ongoing Treatment.

Salient Features

History Physical examination Laboratory findings

 Chronic  Obese  CXR: Suggestive of Pulmonary

productive cough  Equal chest Tuberculosis
for 11 months expansion, clear  CT scan result:
 Fever and chills breath sounds 1. Reticulonodular densities in
 Dyspnea  No abdominal both lungs are primarily
 Weight loss of tenderness, no considered to represent
16kgs in 1 year hepatosplenomeg infectious process such as
 Chronic Kidney aly tuberculosis. The left upper
Disease  No palpable lymph lobe consolidation may be
 Diabetes Mellitus nodes part of the considered
Type 2, with tuberculosis or may represent
maintenance concomitant pneumonia.
medications 2. Cavitary lesion in the right
 Hypertension, upper lobe and the pulmonary
with nodules in the left upper lobes
maintenance are likely part of infectious
medications process.
 Multiple sexual 3. Parenchymal fibrosis, both
partners upper lobe.
 Gene-Xpert: MTB detected low;
Rif resistance no detected

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Differential Diagnosis

Differential Rule In Rule Out

Community-  History of chronic productive  (-) crackles/rales

Acquired cough with whitish sputum,  (-) myalgia
Pneumonia fever  (-) reduced chest
 CT scan result suggests expansion
concomitant TB and  previously diagnosed
pneumonia as PTB

Cannot totally rule out

Lung Carcinoma  Age 58 years old, male  No family history of

 Chronic productive cough
 Weight loss, dyspnea
 CT scan: pulmonary
nodules in the left upper and
left lower lobe
malignancy
 (-) hemoptysis
 (-) chest pain
Cannot totally rule out

Bronchial Asthma  History of chronic productive  No family history of

cough bronchial asthma
 Dyspnea  No personal history of
bronchial asthma
 No history of allergies
 PE: clear breath
sounds

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 PERTINENT DIAGNOSTICS

1. Chest CT Scan (May 21,2019)

 2.7 x 3.9 cm ovoid soft tissue density in the perihepatic region adjacent to
segment II
 Atrophic left kidney
 Reticulonodular densities in both lungs are primarily considered to represent an
infectious process such as TB.
 Left upper lobe consolidation
 Cavitary lesion in right upper lobe
 Pulmonary nodules in left upper and lower lobes
 Parenchymal fibrosis, both upper lobes

2. Xpert MTB-RIF Assay (June 7, 2019)

 MTB detected, low
 Rif resistance not detected

Baseline Diagnostics

1. Blood Chemistry

May 5, 2019:

Parameter Result Reference Value

Uric Acid 3.7 mg/dL 2.6-7.2 mg/dL

ALT (SGPT) 20 IU/L 10-40 IU/L

June 12, 2019:

Parameter Result Reference Value

Creatinine 6.80 mg/dL 0.51-1.17 mg/dL

ALT (SGPT) 12.5 U/L 10-50 U/L

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 TREATMENT PLAN

A. Pre-treatment Clinical Evaluation

1. History
2. Physical Examination
i. Baseline Visual Acuity (using Snellen and color perception
charts)

B. Diagnostics
1. Baseline Laboratory
i. CBC
ii. SGPT, SGOT
iii. Serum creatinine
iv. BUN

C. Therapeutics
1. Category I Treatment Regimen - 2 HRZE/ 4HR
i. Combination tablets for 2 months as Intensive Phase
- Isoniazid (H)
- Rifampicin (R)
- Pyrazinamide (Z)
- Etambutol (E)
ii. Two (2) combination tablets for 4 months as Continuation
Phase
- Isoniazid (H)
- Rifampicin (R)
iii. Dosage and dosage schedule
- Mondays, Wednesdays, Fridays
o Isoniazid 10mg/kg
o Rifampicin 15mg/kg
o Pyrazinamide 30mg/kg
o Ethambutol 20mg/kg
- Tuesdays, Thursdays, Saturdays, Sundays
o Isoniazid 10mg/kg
o Rifampicin 15mg/kg

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 Drug Change in Recommended Dose and Frequency for patients
frequency? with creatinine clearance <30mL/min or for
patients receiving hemodialysis

Isoniazid No change 300 mg once daily; or 900 mg three times per week

Rifampicin No change 600 mg once daily; or 600 mg three times per week

Pyrazinamide Yes 25-35 mg/kg per dose three times per week (not
daily)

Ethambutol Yes 15-25 mg/kg per dose three times per week (not
daily)

2. Monitoring
i. Baseline Complete blood count (CBC)
ii. Baseline and monthly SGPT, SGOT, Creatinine, BUN,
Serum Potassium
iii. Direct Sputum Smear Microscopy for 2nd, 5th or 6th month
of treatment
iv. Monitor for advance drug reaction

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 CASE DISCUSSION

Epidemiology
Tuberculosis (TB) is one of the oldest diseases known to affect humans and is said
to have emerged around 70,000 years ago. It is caused by the bacteria Mycobacterium
tuberculosis complex, a rod-shaped, non-spore forming, acid fast bacillus. About 95% of
the cases of Tuberculosis is in developing countries and is estimated in 2014 that the
epidemiological burden of TB in the Philippines. The estimated epidemiological burden
of tuberculosis in the Philippines has a prevalence rate of 438 (385–495) per 100,000
population (Kasper, et al., 2018).
Standard treatment of active tuberculosis consists of Isoniazid (INH), Rifampin
(RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in
treating active TB, it is associated with many adverse drug reactions (ADRs) and poses
a significant challenge to completion of treatment. Incidence of ADRs due to DOTS
therapy was 69.01%. Majority of cases suffered from GI symptoms (Marra, et al., 2007)

Etiology and Transmission

Mycobacterium tuberculosis is a rod-shaped, non-spore-forming, thin aerobic
bacterium measuring 0.5 μm by 3 μm. Mycobacteria, including M. tuberculosis, are
often neutral on Gram’s staining. However, once stained, the bacilli cannot be
decolorized by acid alcohol; this characteristic justifies their classification as acid-fast
bacilli. Humans and guinea pigs are highly susceptible to M tuberculosis infection, but
fowl and cattle are resistant (Geo, et al., 2007).
TB is transmitted through coughing, sneezing, or speaking, as droplets are
suspended in the air, and inhaled. Crowding in poorly ventilated rooms is one of the
most important factors in the transmission of tubercle bacilli. TB infection starts int the
alveolar air sacs in the lungs. They are taken up by macrophages via phagocytosis but
are not killed off due to its mycolic acid capsule. TB is a granulomatous infection, and
Macrophages, T lymphocytes, B lymphocytes, and fibroblasts aggregate to
form granulomas, with lymphocytes surrounding the infected macrophages. When other
macrophages attack the infected macrophage, they fuse together to form a giant
multinucleated cell in the alveolar lumen. This results in the neutralization of the bacilli
and the prevention of its further spread. There is necrotic material seen in the center of
the granuloma, which resembles soft cheese, which is also termed as caseous necrosis
(Kasper, et al., 2018).

Clinical Manifestations
Pulmonary Tuberculosis often presents as a cough of at least 2 weeks,
associated with fever, hemoptysis, night sweats, anorexia, chest or back pain not
referrable to musculoskeletal disorders, malaise, shortness of breath and weight loss.

15
Diagnostics
1. DSSM
For the diagnostic evaluation of PTB, two (2) sputum specimens should be
obtained for DSSM. Same day (spot-spot) strategy using 2 consecutive
specimens collected 1 hour apart is recommended for direct Ziehl-Neelsen
microscopy.
A case of PTB is already considered bacteriologically confirmed if at least
one (1) sputum smear is positive for acid-fast bacilli.

2. TB culture
TB culture remains the gold standard for TB diagnosis. If available,
sputum TB culture can be requested in the diagnostic work-up of TB, specifically
in ruling out NTM. The long turnaround time of results, limited access and cost of
test limits its routine use. TB culture should be performed preferably in quality
assured culture centers recommended by the National TB Program. If culture-
positive for Mycobacterium tuberculosis (MTB), case is bacteriologically-
confirmed PTB.

3. Chest X-ray
Chest x-ray is a good screening test to identify presumptive PTB.
Together with a good clinical history, a good quality chest x-ray film is needed to
initially guide the clinician in the identification of presumptive PTB for further
bacteriologic confirmation.
It should be performed for all smear-negative presumptive PTB. If
available, Xpert MTB/Rif should be requested among sm rnegative presumptive
TB cases with radiologic findings suggestive of PTB with no risk for drug-
resistant TB or HIV-associated TB. Chest X-ray will reveal a characteristic Ghon
focus.
It is bacteriologically confirmed via Direct Sputum Smear Test, rapid
diagnostic modalities such as Xpert MTB/Rif, or Sputum Culture, which remains
as the gold standard for diagnosis (Philippine Coalition Against Tuberculosis,
2016)
.
4. Xpert MTB/RIF
If available, sputum Xpert MTB/Rif can be requested in the following
clinical situations:
• As initial diagnostic test in adults with presumptive TB
• As follow-on test to smear-negative patients with chest x-ray
findings suggestive of active PTB
• As initial diagnostic test for presumptive drug-resistant TB In comparison
with smear microscopy, Xpert MTB/Rif increased TB detection among
culture-confirmed cases by 23%

16
 5. Tuberculin Skin Test (TST)
TST cannot be used to diagnose active PTB.

Chronic Kidney Disease and TB

The link between active tuberculosis (TB) and chronic kidney disease (CKD) was
first reported in 1974 involving dialysis patients in New York Veterans Administration
Hospital showing an increased susceptibility of patients maintaining hemodialysis to
tuberculosis infection. CKD patients are in an immunodeficient state, owing to multiple
factors such as oxidative stress and inflammation, 5-hydroxyvitamin D deficiency, and
malnutrition, which ultimately leads to functional abnormalities in a variety of immune
cells including B and T cells, neutrophils, monocytes, and natural killer cells
(Romanowski, 2016). This results in an impaired cell-mediated immunity leaving them
susceptible to infectious complications. This vulnerability allows progression of active
TB infection after a recent exposure of Mycobacterium tuberculosis or a reactivation of a
latent TB infection from a distant exposure. In a study done by Cho, et al, (2019), data
showed that the risk of TB increases with the progression of the disease evidenced by
the inverse relationship of patient's risk and GFR suggesting a gradual impairment of
the host's ability to prevent an initial infection or reactivation of a latent infection.
On a different study, Park, et. al, (2019) defined the different risk factors for pre-
dialysis CKD patients which was old age, men, current smoker, low income, lower BMI,
Kidney Disease Improving Global Outcomes CKD Stage 1 or 4/5 without dialysis,
previous use of immunosuppressants, diabetes mellitus and chronic obstructive
pulmonary disease.
Tuberculosis in CKD patients have an increased extrapulmonary involvement,
atypical clinical presentation, and nonspecific symptoms which makes it difficult to
diagnose the patient (Vikrant, 2019). Patients may present symptoms which mimic
uremia such as fever, anorexia and weight loss (Romanowski et. al, 2016). This often
leads to a delay in diagnosis which could be detrimental to the patient.

Primary Management of TB and Chronic Kidney Disease

Renal failure is recognized as a risk factor for developing tuberculosis (TB).
Extrapulmonary TB is more common in patients with chronic renal disease when
compared to those with normal renal function. As a rule, patients with chronic renal
failure should not receive aminoglycosides and should receive ethambutol only if serum
drug levels can be monitored. Isoniazid, rifampin, and pyrazinamide may be given in the
usual doses in cases of mild to moderate renal failure, but the dosages of isoniazid and
pyrazinamide should be reduced for all patients with severe renal failure except those
undergoing hemodialysis.
In a study done by Melburn, et.al (2010), the pharmacological properties of
antituberculosis drugs determine how their levels are likely to be influenced by renal
failure, clearance during dialysis and also their interaction with immunosuppressive
drugs used in patients undergoing renal transplantation. Overall, in patients with CKD
the incidence of adverse effects attributable to their antituberculosis chemotherapy is
significantly higher than that reported in patients with normal renal function.4 In addition,

17
in a journal by Eastwood et.al (2001), it stated that care is required in the use of
streptomycin, other aminoglycosides, and ethambutol because these are wholly
excreted via the kidney. Ethambutol causes optic neuritis, which may be irreversible,
and reduced doses should be given according to the GFR. Streptomycin and other
aminoglycosides are ototoxic and nephrotoxic and should be avoided if possible in
patients with impairment of renal function, especially those on cyclosporin, because
they have a high risk of nephrotoxicity. Encephalopathy is an uncommon complication
of isoniazid therapy and usually is preventable by the prescription of pyridoxine (25 to
50 mg/d). A few patients on hemodialysis have developed isoniazid-induced
encephalopathy that did not respond to pyridoxine, but the condition resolved when
isoniazid was withdrawn. Rifampicin increases the rate of metabolism of a wide range of
drugs, including corticosteroids, cyclosporin, and tacrolimus, which often are given to
transplant patients. Regular measurement of blood concentrations of cyclosporine and
tacrolimus in such patients is recommended.5
In line with this, Isoniazid and Rifampicin are eliminated by biliary excretion--
these drugs, therefore, can be given in normal dosages to patients with renal failure.
Patients with severe renal failure should receive Isoniazid with Pyridoxine to prevent
peripheral neuropathy. Streptomycin, Ethambutol and metabolites of Pyrazinamide are
excreted by the kidney, and doses should be adjusted. If possible, Streptomycin should
be avoided in patients with renal failure. It would therefore be possible to give a 4-drug
FDC (HRZE) three times per week and then give a 2-drug FDC (HR) for the rest of the
week during the intensive phase. Continuation phase may proceed with 4HR.
Otherwise, another safe option is 2HRZ/4HR. It is recommended that anti-TB
medications be taken after hemodialysis.

Monitoring
Monitoring of response to treatment is done to assess the effectiveness of the
treatment as well as surveillance of the possible adverse effects brought about by the
medicines. In patients treated with first in line drugs, sputum smear microscopy is done
once at the end of intensive phase of the treatment. If smear microscopy is positive after
three months of treatment, XpertMTB/Rif, sputum culture and DST is done confirm the
possibility of drug resistance. Patients with positive DST result should be referred to a
PMDT center. All patients should be monitored clinically. Body weight is a useful
indicator that should also be monitored in order to adjust medication doses accordingly.

Prognosis
If properly treated, TB caused by drug-susceptible strains is curable in the vast
majority of cases. Active, drug-susceptible TB disease is treated with standard 6-month
course of 4 antimicrobial drugs that are provided with information, supervision and
support to the patient by health workers or trained volunteers. Without such support,
treatment adherence can be difficult, and the disease can spread. The vast majority of
TB cases can be cured when medicines are provided and taken properly. If untreated,
the disease may be fatal within 5 years in 50–65% of cases.

18
 Balancing side effects against effective tuberculosis (TB) treatment in Chronic
Kidney Disease (CKD) can be difficult leading to variations in management. Continuous
monitoring of kidney function and treatment of CKD by dialysis remains crucial to the
overall outcome of treatment. Careful monitoring of patients is essential as side effects
(mainly neuropsychiatric problems, hepatitis and optic neuropathy) are noted to occur at
higher levels in patients with renal failure and especially those on dialysis.

19
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