Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

BACKGROUND & AIMS: Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. METHODS: 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. RESULTS: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. CONCLUSIONS: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. TRIAL REGISTRATION: www.pactr.org ID number: PACTR201106000300631.

Testing independence of bivariate interval-censored data using modified Kendall's tau statistic.

In this paper, we study a nonparametric procedure to test independence of bivariate interval censored data; for both current status data (case 1 interval-censored data) and case 2 interval-censored data. To do it, we propose a score-based modification of the Kendall's tau statistic for bivariate interval-censored data. Our modification defines the Kendall's tau statistic with expected numbers of concordant and disconcordant pairs of data. The performance of the modified approach is illustrated by simulation studies and application to the AIDS study. We compare our method to alternative approaches such as the two-stage estimation method by Sun et al. (Scandinavian Journal of Statistics, 2006) and the multiple imputation method by Betensky and Finkelstein (Statistics in Medicine, 1999b).

The use of biomarkers for assessing HAART-associated renal toxicity in HIV-infected patients.

Renal toxicity has become an important issue in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Several biomarkers are available for monitoring renal function, although no consensus exists on how best to apply these tools in HIV infection. The best biomarker is the glomerular filtration rate (GFR), and several creatinine-based estimates equations of GFR are widely used in HIV infection, with clinical advantages for the equation developed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Although serum cystatin C has been proposed as a more sensitive marker of renal dysfunction in HIV infection, it may be affected by ongoing inflammation. Tubular dysfunction can be simple or complex, depending on whether the tubular transport of one or more substances is affected. Multiple renal tubular dysfunction or Fanconi syndrome is characterized by alterations in the reabsorption of glucose, amino acids, phosphate and often also bicarbonate. Therefore, Fanconi syndrome would be the tip of the iceberg, and the most unusual and severe manifestation. In the last years, several low molecular weight proteins as markers of tubular alteration, including retinol-binding protein, b2-microglobulin, and neutrophil gelatinase associated lipocalin have become available. Different studies have shown differences in urine concentrations of these proteins in patients receiving tenofovir, but again, no consistent data have shown their clinical usefulness in predicting the clinical consequences of tubular alteration. Thus, we review findings from recent studies performed in this area to describe the performance of new biomarkers for renal damage in HIV-infected patients.

Simultaneous measurement of urinary albumin and total protein may facilitate decision-making in HIV-infected patients with proteinuria.

OBJECTIVE: We recently showed that a urine albumin/total protein ratio (uAPR) <0.4 identifies tubular pathology in proteinuric patients. In tubular disorders, proteinuria is usually of low molecular weight and contains relatively little albumin. We tested the hypothesis that uAPR is useful in identifying tubular pathology related to antiretroviral use in HIV-infected patients. METHODS: We retrospectively identified urine protein/creatinine ratios (uPCRs) in HIV-infected patients. A subset of samples had uPCR and urine albumin/creatinie ratio (uACR) measured simultaneously. We classified proteinuric patients (uPCR >30 mg/mmol) into two groups: those with predominantly 'tubular' proteinuria (TP) (uAPR <0.4) and those with predominantly 'glomerular' proteinuria (GP) (uAPR ≥ 0.4). RESULTS: A total of 618 of 5244 samples from 1378 patients had uPCR ≥ 30 mg/mmol. uAPRs were available in 144 patients: 46 patients (32%) had TP and 21 (15%) GP; the remainder had uPCR <30 mg/mmol. The TP group had a higher fractional excretion of phosphate compared with the GP group (mean 27% vs. 16%, respectively; P<0.01). Patients with TP were more likely to be on tenofovir and/or a boosted protease inhibitor compared with those with GP. In 18 patients with heavy proteinuria (uPCR >100 mg/mmol), a renal assessment was made; eight had a kidney biopsy. In all cases, the uAPR results correlated with the nephrological diagnosis. CONCLUSIONS: In HIV-infected patients, measuring uAPR may help to identify patients in whom a renal biopsy is indicated, and those in whom tubular dysfunction might be an important cause of proteinuria and which may be related to antiretroviral toxicity. We suggest that this would be useful as a routine screening procedure in patients with proteinuria.

Evaluation of arsenic, cadmium, lead, nickel, and zinc in biological samples (scalp hair, blood, and urine) of tuberculosis and diarrhea male human immunodeficiency virus patients.

BACKGROUND: The consequence of a deficiency in trace elements has been associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) disease progression and mortality. This study examined the association between high scalp hair and blood arsenic, cadmium, lead, and nickel concentrations and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). METHODS: The study was performed on sixty two male HIV+ patients (HIV-1) from different cities of Pakistan. The patients were divided in two groups according to secondary infections (tuberculosis, diarrhea, and high fever). The biological samples (scalp hair, blood, and urine) were collected from AIDS patients, and for comparative study 120 healthy subjects (males) of same age group (31 - 45 years), socio-economic status, localities, and dietary habits were also included. The elements in the biological samples were analyzed by electrothermal atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked using certified reference materials (CRMs) and with values obtained by conventional wet acid digestion method on same CRMs. RESULTS: The results indicated significantly higher levels of As, Cd, Ni, and Pb in the biological samples (scalp hair, blood, and urine) of male HIV-1 patients, compared with control subjects. It was observed that the high levels of these toxic elements may be predictors for secondary infections in HIV-1 patients. There was a significant increase in mean values of As, Cd, Ni, and Pb in whole blood, scalp hair, and urine samples of three groups of AIDS patients as compared to a controlled healthy male group (p < 0.001). CONCLUSIONS: These data present guidance to clinicians and other professionals investigating toxicity of As, Cd, Ni, and Pb in biological samples of AIDS patients.

Increased urinary free immunoglobulin light chain excretion in patients with multiple sclerosis.

BACKGROUND: Plasma and B cells are implicated in multiple sclerosis (MS) and produce free light chains (FLC) that are excreted in urine. OBJECTIVE: To confirm that demyelinating diseases (DD) cause increased urinary FLCs. METHOD: Urinary FLC in 50 patients with DD were compared to 20 patients with posterior uveitis (PU), 19 with AIDS, 34 with rheumatoid arthritis (RA) and 19 normal controls (NC). RESULT: Subjects with DD, PU, RA and AIDS have higher urinary FLCs than NC (p<0.01). Urinary FLCs did not correlate with gadolinium-enhancing lesions on MRI. CONCLUSIONS: Urinary FLCs are raised in DD. Further studies are required to see if they correlate with disease activity.

Detection of Histoplasma capsulatum antigen in Panamanian patients with disseminated histoplasmosis and AIDS.

Histoplasmosis is a common endemic mycosis in the Americas, often causing severe disease in patients with AIDS. Antigen detection has become an important method for rapid diagnosis of histoplasmosis in the United States but not in Central or South America. Isolates from patients in the United States are predominantly found to be class 2 isolates when typed using the nuclear gene YPS3, while isolates from Latin America are predominantly typed as class 5 or class 6. Whether infection with these Latin American genotypes produces positive results in the Histoplasma antigen assay has not been reported. In this study, we have compared the sensitivity of antigen detection for AIDS patients from Panama who had progressive disseminated histoplasmosis to that for those in the United States. Antigenuria was detected in the MVista Histoplasma antigen enzyme immunoassay (EIA) in 95.2% of Panamanian cases versus 100% of U.S. cases. Antigenemia was detected in 94.7% of the Panamanian cases versus 92% of the U.S. cases. Two clinical isolates from Panama were typed using YPS3 and were found to be restriction fragment length polymorphism class 6. We conclude that the MVista Histoplasma antigen EIA is a sensitive method for diagnosis of histoplasmosis in Panama.

Thyroid hormone: a "prime suspect" in human immunodeficiency virus (HIV/AIDS) patients?

Acquired Immunodeficiency Syndrome (AIDS) is the final and most serious stage of the disease caused by human immunodeficiency virus. The Immune system is the target of AIDS. We investigate presently any possible involvement of thyroid hormone, the deficiency of which gives rise to oedema and susceptibility to nonspecific infections; with a view to finding the primary factor seeding the disease. It has been reported that circumcision reduced the incidence of HIV/AIDS infection. Beyond circumcision however there might be some constitutional factor that comprises HIV infection to clinical AIDS. It is against this background that our research team turned to possible dyshormonopoisis and to thyroid hormone as a prime suspect among other possible factors that cause clinical AIDS. Moreover the hormone has been reported to be crucial for optimum immune function. A population of 200 seropositive AIDS patients were investigated against a control of 50 subjects made up of 25 healthy circumcised males and 25 healthy females; all of who were seronegative for the disease. The parameters investigated include thyrotropin (TSH), Thyroxine (T4), Total protein (TP), Albumin (Alb), Globulin (Glob), Immune complex (IC3) and Bence Jones proteins (BJP) levels in serum or urine. All seropositive clinically HIV/AIDS patients were hypothyroid. Seronegatives had significantly higher T4, TP, and Alb levels at P < 0.001 and P < 0.05 for Glob than seropositives. Seropositive females exhibited significant (P < 0.001) higher levels of IC3 than seronegative males. The globulin levels of all HIV patients were significantly (P < 0.05) higher than control. BJP was also isolated in the urine of patients. The findings suggest that thyroid hormone deficiency is a primary culprit for the other inert or dormant factors to be activated.

Niacin metabolite excretion in alcoholic pellagra and AIDS patients with and without diarrhea.

OBJECTIVE: Malnourished patients with the acquired immunodeficiency syndrome (AIDS) can develop pellagra-like manifestations such as dermatitis, diarrhea, and dementia; therefore, we tested the hypothesis that patients with AIDS and diarrhea would have niacin depletion. This study compared 24-h urine excretion of N1-methyl-nicotinamide (N1MN) among patients with pellagra and patients with AIDS who did and did not have diarrhea. METHODS: Three groups were studied: G1 (patients with AIDS and diarrhea, n = 5); G2 (patients with AIDS and no diarrhea, n = 7), and G3 (patients with alcoholic pellagra and without the human immunodeficiency virus, n = 8). Diarrhea was defined as the production of at least three liquid stools per day over 3 to 5 d. Studies included mucosal intestinal biopsy, malabsorption tests, detection of parasites in stool, and serum albumin measurements. Semiquantitative food-frequency questionnaire, anthropometry, and daily urinary N1MN excretion were also determined. Groups were matched in relation to age, sex, presence of parasites in stool, and intestinal absorption results. RESULTS: G1 had normal intestinal examination by light microscopy and no parasites in stools. G2 group showed lower levels of serum albumin (2.6 +/- 0.3 g/dL) when compared with G1 (3.4 +/- 0.3 g/dL) and G3 (3.1 +/- 0.7 g/dL). Except for patients with pellagra, groups met their energy requirements. Patients in G3 (0.013, 0.01-0.081 mg/dL) and G1 (0.062, 0.001-0.33 mg/dL) excreted smaller amounts of N1MN in urine than did those in G2 (0.63, 0.02-2.9 mg/dL). CONCLUSIONS: Patients with AIDS and diarrhea excreted less N1MN in urine than did those without diarrhea. These patients may have an impaired niacin nutritional status, possibly associated with increased metabolic needs.

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults.

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW it immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease.

Nitric oxide (NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of.NO in the development of progressive disease we measured the NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit : creat. urine) and neopterin (neopt : creat.urine) to creatinine ratios compared to NC subjects. (Median[25th - 75th%] nit : creat.urine: NC=1183[962 - 1365] vs DD=1245[875 - 2403], AIDS=1686[1231 - 2531], and RA=1950[1214 - 2726] mumol/mol, P<0.001 and median[25th - 75th%] neopt : creat.urine: NC=99[76 - 151] vs DD=163[119 - 266], AIDS=972[653 - 1456], and RA=389[257 - 623] mu mol/mol, P<0.001). Patients with early DD and RR MS had significantly elevated nit : creat.urine compared to patients with progressive MS (nit : creat. urine: 1612[1020 - 2733] vs 1159[790 - 1641] mu mol/mol, P=0.006). The nit : creat.urine and neopt : creat.urine did not correlate with clinical relapse or MRI activity. Excretion of.NO metabolites is increased in patients with early or relapsing-remitting disease.NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

Azaftig, a urinary proteoglycan from a cachectic cancer patient, causes profound weight loss in mice.

Cachexia is a complex medical condition characterized by significant weight loss associated with decreased body fat and protein; the condition may present itself with or without anorexia. We have isolated and partially characterized a proteoglycan (azaftig) from the urine of cancer and AIDS patients experiencing weight loss. When given to mice, the purified azaftig resulted in a significant decrease in body weight and body fat without any effect on appetite. The results of these studies show that azaftig may be one of the many factors participating in the emergence of the cachectic state.

[Urinary excretion of vitamin A and thiobarbituric acid reactive substances in AIDS patients]. / Excreção urinária de vitamina A e substâncias reativas ao ácido tiobarbitúrico em pacientes com AIDS.

In the present investigation 28 serologically positive HIV-1 patients, 16 patients with AIDS (< 200/mm3 CD4+ T lymphocytes) and 12 with HIV-1 (200 to 500/mm3 CD4+ T lymphocytes) were studied. The Control Group consisted of 11 healthy individuals. The occurrence of alterations in the anthropometric parameters were higher in AIDS patients, compared to HIV-1 and controls patients, indicating a greater level of malnutrition. All individuals in present study showed normal plasma vitamin A levels. Contrasting, urinary excretion of vitamin A were higher in the AIDS Group (0.23 +/- 0.20 mumol/l) than in the HIV Group (0.19 +/- 0.12 mumol/l) and considerably higher than in the Control Group (0.06 +/- 0.05 mumol/l). Urinary excretion of TBARS also were higher in AIDS Group (3.34 +/- 2.65 mumol/l) compared to HIV (1.71 +/- 0.74 mumol/l) and Control Group (1.70 +/- 0.75 mumol/l). These results demonstrate a greater level of malnutrition and elevate excretion of vitamin A and SRATB in urine of AIDS patients. Therefore, monitoring of nutritional status, especially in relation to vitamin A is recommended for patients with HIV and AIDS.

JC virus remains latent in peripheral blood B lymphocytes but replicates actively in urine from AIDS patients.

JC virus (JCV) is thought to reach the central nervous system by a vascular route. To determine whether JCV is conveyed in peripheral blood as latent or reactivated virus, blood leukocytes, plasma, and urine from 50 AIDS patients and plasma and B lymphocytes from 60 AIDS patients were investigated. Peripheral blood from 88 human immunodeficiency virus-negative blood donors was studied. Nested polymerase chain reaction assays allowed the identification of JCV T DNA and VP1 mRNAs. The latter indicate viral replication. Blood harbored JCV DNA in 31.8% of AIDS patients (only 2.3% of blood donors; P > .001) and urine in 56%. VP1 mRNAs were detected in blood of 1 AIDS patient. Notably, 38% of DNA-positive urine samples and 10 cerebrospinal fluid samples (CSF) from AIDS patients with progressive multifocal leukoencephalopathy contained JCV mRNAs. Thus, JCV was significantly more frequent in blood from AIDS patients than from controls, but, in most instances, it was latent, whereas active replication was detected in urine and CSF.

Twenty-four-hour urinary free cortisol in patients with acquired immunodeficiency syndrome.

Many patients with acquired immune deficiency syndrome (AIDS) have symptoms consistent with adrenal insufficiency, but only a small subset of these patients meet criteria for adrenal insufficiency during a short corticotropin (ACTH) stimulation test. We hypothesized that patients with AIDS and symptoms of adrenal insufficiency who produce normal amounts of cortisol in response to administration of 0.25 mg cosyntropin may nevertheless produce lower amounts of cortisol in a course of 24 hours than comparably sick AIDS patients without symptoms of adrenal insufficiency or comparably sick patients without AIDS. We studied four groups of male patients: AIDS patients with symptoms suggestive of adrenal insufficiency but with a normal response to cosyntropin (group I), AIDS patients without symptoms suggestive of adrenal insufficiency (group II), human immunodeficiency virus (HIV)-negative patients with serious acute or chronic illness (group III), and healthy subjects (group IV). The following variables were examined: age, CD4 cell count, Acute Physiologic and Chronic Health Evaluation (APACHE) score, serum cortisol and plasma ACTH at baseline; serum cortisol at 30 and 60 minutes after intravenous administration of 0.25 mg cosyntropin; and 24-hour urinary free cortisol. The four groups had a similar mean age and baseline plasma ACTH and serum cortisol levels. However, a change in cortisol from baseline to 30 and 60 minutes after administration of cosyntropin was significantly smaller in both groups of AIDS patients than in the sick patients without AIDS and normal subjects. There were also differences noted between the two groups of AIDS patients: both baseline and stimulated levels of cortisol tended to correlate directly with ACTH levels in patients without symptoms of adrenal insufficiency, while this relationship appeared to be inverse in patients with symptoms suggestive of adrenal insufficiency (r = -.57 to -.7, P < .05 to .14). The 24-hour urinary free cortisol levels were similar among all groups, but correlated strongly with baseline and stimulated serum cortisol levels only in patients with AIDS and symptoms of adrenal insufficiency (r = .8 to .9, P < .002 to .015). We conclude that (1) AIDS patients with and without symptoms of adrenal insufficiency may have either normal adrenal function or somewhat suboptimal adrenal reserve as demonstrated by a blunted cortisol response during the short ACTH stimulation test in comparison to HIV-negative comparably sick patients or healthy subjects; and (2) 24-hour urinary free cortisol is not a useful test for detection of subtle abnormalities of adrenal function in patients with AIDS.

[Chronic HIV- and chronic HBV infection with hematuria and proteinuria]. / Chronische HIV- und chronische HBV-Infektion mit Erythrozyturie und Proteinurie.

HISTORY AND CLINICAL FINDINGS: A medical examination, undertaken in an apparently healthy 30-year-old man because of his occupational exposure to chemicals, revealed haematuria and proteinuria. Physical examination was unremarkable except for oral hair-leukoplakia and swelling of the cervical, supraclavicular, axillary and inguinal lymph nodes. INVESTIGATIONS: Examination of the urine demonstrated selective glomerular proteins (1.5 g/24 h) and dysmorphic erythrocytes. SGOT and SGPT activities were raised (73 and 129 IU/l, respectively). Active hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) infections were demonstrated virologically. The CD4+ count in blood was reduced to 200 cells/microliter. Renal biopsy showed an IgA nephropathy. TREATMENT AND COURSE: Antiretroviral treatment with zidovudine and lamivudine were started. SGOT and SGPT activities and HIV load fell steadily, while CD4+ cell count rose markedly. Renal functions have remained stable during the past 6 months. CONCLUSION: Signs of glomerular damage are not unusual in systemic diseases, tumors or infections (Hepatitis B and HIV in this case) and they may be the first manifestations of the underlying disease.

Excreçäo urinaria de vitamina A e substancias reativas ao acido tiobarbiturico em pacientes com AIDS / Urinary excretion of vitamin A and thiobarbituric acid reactive substances in AIDS patients

Foram estudados 28 pacientes com sorologia positiva para HIV-1, sendo 16 classificados como aideticos (linfocitos-T CD4+ < 200/mm3) e 12 portadores do HIV-1 (linfocitos-T CD4+ entre 200 e 500/mm3), o grupo controle foi composto por 11 individuos saudaveis. A ocorrencia de alteracoes de parametros antropometricos foi alta nos pacientes com AIDS, quando comparados com pacientes com HIV-1 e controles, indicando um grau acentuado de desnutricao nestes pacientes. Todos os individuos estudados apresentaram niveis normais de vitamina A plasmatica. Verificou-se uma maior excrecao urinaria no grupo com AIDS (0,23 + ou - 0,20 umol/l) em relacao ao grupo HIV (0,19 + ou - 0,12 umol/l) e muito maior que o controle (0,06 + ou - 0,05 umol/l)...