Severe Impairment of Solute-Free Water Clearance in Patients With HIV Infection

Study Overview
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Brief Summary
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The objective of the present study is to analyze the overall tubular function, and in particular that from the proximal tubule and the thick ascending loop of Henle (TALH) in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with seronegative controls, by applying a validated tubular physiological test known as Low sodium infusion test. Hypothesis is that patients with HIV infection and normal renal function will show subclinical tubular abnormalities compared with seronegative controls

Detailed Description
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Renal disease is a well recognized complication among patients with HIV infection. Either viral infection itself and the use of some antiretroviral drugs contribute to this serious non AIDS-defining condition that may affect both the glomeruli and the renal tubules. The thick ascending loop of Henle constitutes the main location for free-water clearance determining kidney´s ability to concentrate and dilute urine in a direct and indirect fashion, respectively.

Official Title
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Severe Impairment of Solute-Free Water Clearance in Patients With HIV Infection

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Low sodium water overload in HIV tenofovir, HIV no tenofovir and seronegative controls


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria are as follows: adult patients (≥18 years old) with confirmed chronic HIV-1 infection who agreed to provide written informed consent. Patients under antiretroviral treatment must had a stable regimen for over six months and undetectable (<50 copies/ml) viral load for at least three months. At study entry all selected patients were confirmed as having normal physical examination, routine clinical laboratory including urinalysis, as well as renal and cardiac ultrasound. Exclusion Criteria: Exclusion criteria include patients with acute HIV infection (< 6 months of disease), personal history of nephropathy, plasma creatinine ≥1.3 mg/dl, Glomerular filtration rate ≤60ml/min/1.73 m² (as determined by Modification of Diet in renal Disease formula), presence of glucosuria/proteinuria (measured in spot urine sample), prior heart failure, concurrent opportunistic infection, chronic active hepatitis B or C, and use of potentially nephrotoxic agents in the prior week before the test (e.g diuretics, angiotensin converting enzyme antagonists, Angiotensin II receptor antagonists or non-steroidal anti-inflammatory agents).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV Tenofovir<br> | Other: Low sodium water overload in HIV tenofovir, HIV no tenofovir and seronegative controls<br>* This test is based on the exploration of the tubular response to an acute fluid load. After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours. Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test. From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed. Since patient inclusion follow up period is one month<br>|
| HIV No tenofovir<br> | Other: Low sodium water overload in HIV tenofovir, HIV no tenofovir and seronegative controls<br>* This test is based on the exploration of the tubular response to an acute fluid load. After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours. Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test. From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed. Since patient inclusion follow up period is one month<br>|
| Seronegative controls<br> | Other: Low sodium water overload in HIV tenofovir, HIV no tenofovir and seronegative controls<br>* This test is based on the exploration of the tubular response to an acute fluid load. After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours. Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test. From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed. Since patient inclusion follow up period is one month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free Water Clearance | Low sodium water overload | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine osmolarity |  | one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Antiretroviral treatment, Renal disease, Renal tubular damage, Free-water clearance