Commentary on: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy/Authors' reply: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy

Abstract

The test is widely used in any clinical setting and the main indication for measuring blood albumin level is to determine the hypoalbuminemia, which can contribute to edema.2 In medical practice, the common conditions that can result in hypoalbuminemia include liver disease, glumerulopathy and protein malnutrition.2 The use of albumin as a biomarker for other conditions is very interesting issue in laboratory medicine. [...]the hypoalbuminemia can be seen in several conditions that have the problem of protein malnutrition. Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy Gerardo Alvarez-Uria*, Manoranjan Midde, Raghavakalyan Pakam, Praveen Kumar Naik Department of Infectious Diseases, Rural Development Trust Hospital, Bathalapalli, AP, India Received: 4 Dec. 2013, Revised: 10 Dec. 2013, Accepted: 14 Dec. 2013, ePublished: 16 Dec. 2013 Corresponding author:

Viroj Wiwanitkit1,2,3*

1Hainan Medical University, China

2Faculty of Medicine, University of Nis, Serbia

3Joseph Ayobabalola University, Nigeria

Received: 30 Oct. 2013, Revised: 05 Nov. 2013, Accepted: 26 Nov. 2013, ePublished: 02 Dec. 2013

Corresponding author: Viroj Wiwanitkit, Email: w viroj{at}yahoo.com

The recent publication entitled "serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy"1 is very interesting. Alvarez-Uria et al. mentioned that "serum albumin can be a useful low-cost diagnostic marker for tuberculosis in HIV infected patients eligible for ART."1 In fact, this conclusion has to be carefully considered. Albumin is a basic biochemistry parameter in clinical practice. The test is widely used in any clinical setting and the main indication for measuring blood albumin level is to determine the hypoalbuminemia, which can contribute to edema.2 In medical practice, the common conditions that can result in hypoalbuminemia include liver disease, glumerulopathy and protein malnutrition.2

The use of albumin as a biomarker for other conditions is very interesting issue in laboratory medicine. Focusing on infection, the aberration of blood albumin level can be observed.3 Of several infections, tuberculosis is widely discussed about its interrelationship with alteration of blood albumin. Extremely low blood albumin level is a common finding in the death cases of tuberculosis.4 Horita et al. recently proposed blood albumin as an important determinant for prognostic scoring of tuberculosis.5 It was found that low blood albumin could effectively predict a poor outcome.4 However, the use of blood albumin determination in the cases with concurrent morbidity is not well understood and the study in this topic is interesting. Of several clinical problems, the important problematic concurrent infection in the patients with tuberculosis is HIV infection. Due to the deterioration of immunity in the HIV infected patients, the emerging of tuberculosis can be expected. The clinical use of blood albumin determination in the cases with HIV infection is a challenging topic. Alvarez-Uria et al. performed a Cohort Study on this topic in India.1 They focused their interest on the feasibility of using blood albumin determination as biomarker to predict tuberculosis in the HIV infected patients.1 Alvarez-Uria et al. found that "the diagnostic accuracy of serum albumin, measured by the area under the receiver operating characteristic curve, to predict tuberculosis was 0.81."1 As Alvarez-Uria et al. reported, the diagnostic property of the albumin was only fair and it could not be used for ruling out tuberculosis. In fact, the hypoalbuminemia can be seen in several conditions that have the problem of protein malnutrition. Both tuberculosis and HIV infection can contribute to the problem of hypoalbuminemia. Focusing on laboratory parameters, hypoalbuminemia is very common in the HIV infected patients.6,7 Graham et al. mentioned that "each 1 g/liter decrease in albumin with HIV-1 acquisition was associated with a 13% increase (p = 0. 01) in the risk of progressing to a CD4 count <200 cells/ mul."6 Altice et al. also mentioned that low blood albumin level suggested "increased risk for HIV, particularly in settings where HIV testing resources are scarce."8

It is no doubt that Alvarez-Uria et al. could not be able to discriminate between the cases with and without tuberculosis. Focusing on the observation that hypoalbuminemia was relating to the poor outcome, it has ever been reported in previous studies. Sudfeld et al. found that this relationship is dependent to CD4+ count; hence, this reflects the nutritional not the immunological problem.9 Dao also found a similar observation that hypoalbuminemia could help predict mortality in HIV infected cases, especially for the first year of initiating ART.10

Conclusively, with or without tuberculosis, hypoalbuminemia could be a good biomarker for predicting poor outcome of HIV infection. On the other hand, with or without HIV infection, hypoalbuminemia could be a good biomarker for predicting poor outcome of tuberculosis. However, the conclusion on the concurrent HIV and tuberculosis infection, the value of hypoalbuminemia in predicting requires further systematic investigation to clarify.

Ethical issues

There is none to be declared.

Competing interests

The authors declare no conflict of interests.

References

1. Alvarez-Uria G, Midde M, Pakam R, Naik PK. Diagnostic and prognostic value of serum albumin for tuberculosis in HIV infected patients eligible for antiretroviral therapy: Datafrom an HIV cohort study in India. Bioimpacts 2013;3:123-8.

2. Makino H. Biochemical profiling. Rinsho Byori 1971;19:599-606.

3. Tominaga K, Toda T, Kudo S, Toda K, Suzuki K. Infectious diseases and serum proteins. Saishin Igaku 1968;23:1701-8.

4. Davis CE Jr, Carpenter JL, McAllister CK, Matthews J, Bush BA, Ognibene AJ. Tuberculosis. Cause of death in antibiotic era. Chest 1985;88:726-9.

5. Horita N, Miyazawa N, Yoshiyama T, Ishigatsubo Y. Prognosis of patients with tuberculosis. Kekkaku 2013;88:565-70.

6. Graham SM, Baeten JM, Richardson BA, Wener MH, Lavreys L, Mandaliya K, et al. A decrease in albumin in early HIV type 1 infection predicts subsequent disease progression. AIDS Res Hum Retroviruses 2007;23:1197- 200.

7. Kaur A, Babu PG, Jacob M, Narasimhan C, Ganesh A, Saraswathi NK, et al. Clinical and laboratory profile of AIDS in India. J Acquir Immune Defic Syndr 1992;5:883-9.

8. Altice FL, Mostashari F, Selwyn PA, Checko PJ, Singh R, Tanguay S, et al. Predictors of HIV infection among newly sentenced male prisoners. J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:444-53.

9. Sudfeld CR, Isanaka S, Aboud S, Mugusi FM, Wang M, Chalamilla GE, et al. Association of serum albumin concentration with mortality, morbidity, CD4 T-cell reconstitution among tanzanians initiating antiretroviral therapy. J Infect Dis 2013;207:1370-8.

10. Dao CN, Peters PJ, Kiarie JN, Zulu I, Muiruri P, Ong'ech J, et al. Hyponatremia, hypochloremia, and hypoalbuminemia predict an increased risk of mortality during the first year of antiretroviral therapy among HIV-infected Zambian and Kenyan women. AIDS Res Hum Retroviruses 2011;27:1149-55.

Authors' reply: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy

Gerardo Alvarez-Uria*, Manoranjan Midde, Raghavakalyan Pakam, Praveen Kumar Naik

Department of Infectious Diseases, Rural Development Trust Hospital, Bathalapalli, AP, India

Received: 4 Dec. 2013, Revised: 10 Dec. 2013, Accepted: 14 Dec. 2013, ePublished: 16 Dec. 2013

Corresponding author: Gerardo Alvarez-Uria, Email: gerardouria{at}gmail.com

We thank Professor Wiwanitkit for highlighting important aspects of hypoalbuminemia in HIV infected patients.1 Hypoalbuminaemia can be the result of inadequate protein intake, malabsorption, reduced production in the liver, increased catabolic state or increased excretion of proteins through the kidneys. In patients with chronic diseases such as cancer, tuberculosis or end stage renal disease, hypoalbuminemia can be explained by a reduced protein intake due to anorexia and by an increased catabolic state due to inflammation. However, recent evidence shows that hypoalbuminemia is more likely to be a marker of inflammation than a marker of malnutrition, and nutritional supplementation is unlikely to raise serum albumin levels.2

HIV infection produces chronic inflammation. Hence, HIV could be a cause of hypoalbuminemia and one could expect a correlation between serum albumin concentrations and CD4 cell counts. However, Sudfeld et al did not observe an association between serum albumin levels and changes in the CD4 cell counts, and the CD4 cell counts did not affect the value of serum albumin for predicting mortality.3 It is possible that hypoalbuminemia could be a marker of inflammation in HIV infected patients and could be used as a predictor of mortality independent of the CD4 cell count.4 Whether the inflammation is produced by HIV itself or by co-infections such as tuberculosis is a matter that deserves further research.

The objective of our study was not to explain the causes of hypoalbuminemia in HIV infected patients, but to explore the usefulness of hypoalbuminemia as a predictor of tuberculosis.5 The vast majority of HIV infected patients with tuberculosis are living in low- and middle-income countries, where the smear microscopy of sputum is most of the time the only available highly specific diagnostic test.6 In our setting, three-quarters of patients diagnosed with tuberculosis had smear negative sputum.7 Even in settings where the Xpert RIF/MTB assay is available, empirical treatment is the rule.8,9 Our study suggested that serum albumin could be useful for clinicians working in resource-poor settings when facing smear-negative HIV infected patients with clinical suspicion of tuberculosis. Patients with hypoalbuminemia will be more likely to have tuberculosis. Patients with higher albumin concentrations are less likely to have tuberculosis and, if they have tuberculosis, they have a better prognosis. The final decision on whether to start anti-tuberculous therapy empirically should not be based solely on the concentration of serum albumin, and other information such as compatible symptoms, physical examination and chest radiography should be taken into account. In Figure 1 we present the hazard ratio and 95% confidence intervals for tuberculosis by serum albumin concentrations using restricted cubic splines (seven knots) and Cox regression. The low cost of the assay and the general availability in health care facilities in resource-poor settings make serum albumin very interesting from a public health point of view. In particular, it could be useful to improve the sensitivity and specificity of the four-symptom screening strategy recommended by the World Health Organization for intensified case finding and isoniazid preventive therapy. However, we agree with Professor Wiwanitkit in that our study has important limitations. It is a retrospective study using routinely collected data in a setting without tuberculosis culture. Only patients who had the serum albumin measured at the time of antiretroviral therapy eligibility were included. Forty-three percent of patients did not have a measurement of the serum albumin and were excluded. Prospective studies are needed to confirm our findings.

Ethical issues

There is none to be declared.

Competing interests

The authors declare no conflict of interests.

References

1. Wiwanitkit V. Commentary: SerumAlbumin for tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy. Bioimpacts 2013;3: 199-200.

2. Friedman AN, Fadem SZ. Reassessment of albumin as a nutritional marker in kidney disease. J Am Soc Nephrol JASN 2010;21:223-230.

3. Sudfeld CR, Isanaka S, Aboud S, Mugusi FM, Wang M, Chalamilla GE, et al. Association of serum albumin concentration with mortality, morbidity, CD4 T-cell reconstitution among tanzanians initiating antiretroviral therapy. J Infect Dis 2013;207:1370-1378.

4. Lang J, Scherzer R, Weekley CC, Tien PC, Grunfeld C, Shlipak MG. Serum albumin and short-term risk for mortality and cardiovascular disease among HIV-infected veterans. AIDS Lond Engl 2013;27:1339-1343.

5. Alvarez-Uria G, Midde M, Pakam R, Naik PK. Diagnostic and prognostic value of Serum Albumin for tuberculosis in HIV infected patients eligible for antiretroviral therapy: Data from an HIV cohort study in India. BioImpacts 2013;3:123-128.

6 Alvarez-Uria G, Azcona JM, Midde M, Naik PK, Reddy S, Reddy R. Rapid Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in HIV-Infected Patients. Comparison of LED Fluorescent Microscopy and the GeneXpert MTB/RIF Assay in a District Hospital in India. Tuberc Res Treat 2012;2012:932862.

7. Alvarez-Uria G, Naik PK, Pakam R, Bachu L, Midde M. Natural history and factors associated with early and delayed mortality in HIV infected patients treated of tuberculosis under directly observed treatment short course (DOTS) strategy: a prospective cohort study in India. Interdiscip Perspect Infect Dis 2012;2012:502012.

8. Yoon C, Cattamanchi A, Davis JL, Worodria W, den Boon S, Kalema N, et al. Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda. PLoS ONE 2012;7:e48599.

9. Hanrahan CF, Selibas K, Deery CB, Dansey H, Clouse K, Bassett J, et al. Time to Treatment and Patient Outcomes among TB Suspects Screened by a Single Point-of-Care Xpert MTB/RIF at a Primary Care Clinic in Johannesburg, South Africa. PLoS ONE 2013;8:e65421.