Serum reference intervals of micronutrients, vitamins, and interleukins among healthy adults in South-Western Nigeria.

Objectives: Clinical decision making depends mostly on appropriate application of numerical pathology reports from laboratory results, interpreted by comparison with reference intervals. We determined serum reference intervals of micronutrients, vitamins, and detectable interleukins among healthy adults in South-Western Nigeria. Design and methods: This prospective study used a priori selection approach in blood-donors. They were screened for conditions that could elicit cytokine production.Serum micronutrients were assayed using Atomic Absorption Spectrophotometry; interleukins and vitamins by high Performance Liquid Chromatography. The reference intervals (RIs) were estimated at 2.5th percentile and 97.5th percentile. Results: One hundred and eighteen (118) apparently healthy subjects, aged 18-56 years; 113 (95.8%) being 18-44years, and 5 (4.2%): 45-56 years; mostly males, 13 (11.02%) females, all Africans of Yoruba ethnicity.Estimated reference limits were: Zinc: 9.49-20.54 µmol/L, Selenium: 0.50-1.11 µmol/L, Copper: 13.86-27.97 µmol/L, Iron: 14.19-32.07 µmol/L, Manganese: 6.24-16.37 nmol/L; Magnesium: 0.78-1.62 mmol/L.Vitamins: A-1.08-2.39 µmol/L; D: 59.89-164.42 µmol/L; E: 7.13-19.45 µmol/L; K: 0.16-0.42 nmol/L; B1: 74.09-201.56 nmol/L; B6: 0.12-0.29 nmol/L; B12: 155.55-407.96 pmol/L; C: 47.74-112.99 µmol/L.Detected interleukins (IL-1 to IL-18): IL-1: 0.58-1.24 ng/L, IL-2: 0.09-0.18 ng/L, IL-3: 0.39-0.89 ng/L, IL-4: 0.27-0.58 ng/L, ….to IL-18: 0.74-1.56 ng/L. Conclusions: The RI derived from this study for serum micronutrient, vitamin and interleukin concentrations are the first published for our population. They are in general agreement with those published from other geographical climes but there are differences at the lower and upper limits of the RI. The study reinforces the importance of deriving RI for the population that a clinical laboratory will serve.

Serum Interleukin-6 and Weight Loss in Antiretroviral-naïve and Antiretroviral-treated Patients with HIV/AIDS: Relationships and Predictors.

BACKGROUND: Cachexia is usually associated with elevated serum interleukin-6 (IL.6) as it stimulates the breakdown of muscle proteins and promotes wasting. OBJECTIVE: A case-control study to evaluate the relationship between weight loss, facial fat loss, and IL-6 in antiretroviral-naïve and treated participants living with HIV/AIDS. METHODS: IL-6 was assayed by High performance liquid chromatography (HPLC) in 97 in consecutive newly diagnosed antiretroviral-naive (ART-naïve) people living with HIV/AIDS (age ≥18 years); and 118 consecutive, age-matched participants currently on Highly Active Antiretroviral Therapy (HAART), using age as a criterion. In the treated group, 78 (66.7%) subjects were on zidovudine, lamivudine with nevirapine (Z+L+N); 27(23.1%) on tenofovir, lamivudine with emtricitabine (T+L+E); 5(4.3%) on zidovudine, lamivudine with emtricitabine (Z+L+E); 4(3.4%) on zidovudine, lamivudine with tenofovir (Z+L+T); 2(1.7%) on lamivudine, tenofovir with nevirapine (L+T+N); 1(0.9%) on tenofovir, zidovudine, emtricitabine (Z+T+E). RESULTS: A total of 215 participants: 97 ART-naive and 118 HAART-treated, age-matched subjects (40.3±9.6 versus 42.7±10.20years, p=0.08). The mean IL-6 was significantly higher in naïve than treated (0.69±0.04 versus 0.66±0.04 pg/ml, p =0.002). In all, 73 subjects experienced weight loss, 56(76.7%) naive, 17(23.3%) treated, p <0.0001, with significantly higher IL-6 in those with weight loss (0.69±0.05 versus 0.67±0.05pg/ml, p= 0.047). Fifty-eight (27.0%) subjects experienced facial fat loss, 49 (84.5%) naïve, and 9 (15.5%) treated, p <0.0001, with significantly higher IL-6 in those with facial fat loss (0.7 ± 0.05 versus 0.67±0.05pg/ml, p= 0.0001). Negative correlation exists between IL-6 and CD4+ count (r=-0.141, p=0.041). In logistic regression, independent predictors of weight loss include: IL-6 (Adjusted Odds Ratio, aOR 1.3, 95%CI 0·1-2·6, p=0.047); HIV duration (aOR 11.6, p <0.0001); AIDS-defining illness (aOR 3.5, p <0.0001); CD4+ count (aOR 3.2, p=0.004); HAART status (aOR 2.7, p<0.0001). CONCLUSION: HIV infection is associated with elevation of serum interleukin-6, which likely contributes to weight and facial fat loss among the treatment-naïve participants; while HAART is associated with suppressed IL-6 levels, thereby ameliorating weight and facial fat loss. Inverse relationship exists between serum IL-6 and CD4+ count; serum IL-6 could differentiate between mild- to moderate and severe immunosuppressive states.

Renal Phosphate Handling in Antiretroviral-naive HIV-Infected Patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. OBJECTIVES: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). METHODS: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ARTnaive, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). RESULTS: eGFR showed significant difference between patients' and controls' medians (47.89ml/ min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 - 2.2) versus 1.1 mmol/L (IQR: 0.3 - 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 - 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96% (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). CONCLUSION: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naive HIV patients.

Effects of Highly Active Antiretroviral Therapy on Albuminuria in HIVinfected Persons.

BACKGROUND: Highly active antiretroviral therapy (HAART), especially tenofovir DFcontaining regimens, has been implicated in albuminuria. OBJECTIVE: We prospectively evaluated the effects of HAART on albumin-to-creatinine ratios (ACRs) in antiretroviral-naïve HIV-infected individuals. METHODS: One hundred and two (102) newly diagnosed, antiretroviral-naïve, human immunodeficiency virus (HIV)-infected persons were treated with Tenofovir disoproxil fumarate/ Emtricitabine/Efavirenz (TDF/FTC/EFV), n=33; Zidovudine/Lamivudine/Nevirapine (ZDV/3TC/NVP), n=53; and Zidovudine/Lamivudine/Efavirenz (ZDV/3TC/EFV), n=16. Diabetes mellitus and hypertension were excluded. ACRs and glomerular filtration rates (eGFR) were estimated at baseline, and at 1, 3, 6 and 9 months post-therapy; the prevalence of albuminuria (ACR ≥ 300mg/g), and microalbuminuria (ACR 30-300mg/g) were similarly estimated. HAART effects on normal ACR (0-30mg/g) were also monitored. RESULTS: At baseline, one patient (0.9%) had nephrotic-range albuminuria with ACR of 2450mg/g. Overall, 8 (7.8%) patients had albuminuria; 53 (51.9%) had microalbuminuria; while 41 (40.2%) had normal ACRs, 28 (27.5% of 102) of which had nonalbuminuric renal insufficiency. eGFR and ACRs improved concurrently on HAART (ACR, Wilks' lambda 0.439, power 0.763, p=0.032); albuminuria improved significantly on all the 3 regimens at 9 months (p=0.006, 0.012 and <0.001 respectively). Microalbuminuria resolved earlier (1 month) with ZDV/3TC/NVP than with TDF/FTC/EFV and ZDV/3TC/EFV (24.31mg/g versus 76.51mg/g and 63.59mg/g; p=0.028, 0.016 respectively). Microalbuminuria relapsed on TDF/FTC/EFV and ZDV/3TC/EFV at 6 months but resolved again at 9 months (66.7 versus 29 mg/g, p=0.006; and 51.2 versus 9.5mg/g, p=0.001 respectively); no relapse on ZDV/3TC/NVP. At 9 months, ZDV/3TC/EFV caused the greatest resolution of microalbuminuria (85.7% decline in ACR from baseline) compared with ZDV/3TC/NVP (72.5% decline) and TDF/FTC/EFV (63.9% decline). In multivariate analyses, predictors of ACR include older age (Odds ratio OR 2.8, p= 0.025); female gender (OR, 3.4, p =0.014); CD4+ (OR 0.99, p=0.002). CONCLUSION: HIV induces renal impairment. Thus, albuminuria, microalbuminuria and nonalbuminuric renal insufficiency are highly prevalent in antiretroviral-naïve HIV-infected persons but nephrotic-range albuminuria is uncommon. Albuminuria and/microalbuminuria and eGFR improve concurrently on HAART (with/without tenofovir DF). Zidovudine-based HAART (ZDV/3TC/NVP) resolves microalbuminuria earlier, and without relapse, unlike Tenovofir-based regimen and zidovudine with efavirenz (ZDV/3TC/EFV).