Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01138241
Recruitment Status : Completed
First Posted : June 7, 2010
Last Update Posted : August 10, 2017
Chulalongkorn University
Kirby Institute
Information provided by (Responsible Party):
The HIV Netherlands Australia Thailand Research Collaboration

June 4, 2010
June 7, 2010
August 10, 2017
March 2010
June 2017   (Final data collection date for primary outcome measure)
to validate eGFR Thai equation in HIV-infected adults [ Time Frame: Blood specimens were drawn to assess plasma radioactivity at 5, 10, 20, 30, 60, 90, 120, 180, and 240 minutes post 99mTc-DTPA injection ]
Test of diagnostic accuracy
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Complete list of historical versions of study NCT01138241 on Archive Site
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  • eGFR by C-G formula, MDRD, CKD-EPI [ Time Frame: June 2010 to May 2011 ]
    The eGFR values will be calculated by the re-expressed IDMS traceable MDRD, C-G, and CKD-EPI.
  • GFR by cystatin C [ Time Frame: June 2010 to May 2011 ]
    Serum for cystatin C levels will be collected at the time of serum creatinine collection. Cystatin C will be measured by quantitative sandwich enzyme immunoassay. GFR will be estimated from the cystatin C measurement using the following equation18: Cystatin C GFR=86.7/cystatin-4.2.
  • GFR by urine 24 hours [ Time Frame: June 2010 to May 2011 ]
    Urine will be collected over a 24-hour period. Verbal and written instructions for collecting urine at home will be given to the patients. Containers (5litres) will be provided for all patients. Creatinine clearance (CrCl) will be calculated using the following equation: CrCl= Urine Cr/Serum cr xQu ; where Qu is the urine volume divided by the time of the actual collection. CrCl estimates will be adjusted for BSA.
  • TDF plasma levels [ Time Frame: June 2010 to May 2011 ]
    TDF plasma concentrations are assessed by using a validated high-performance liquid chromatography (HPLC)-mass method. Blood will be collected in lithium-heparin or sodium-heparin tube at mid dose (10-12 hr post dose of TDF). The exact times of sampling will be recorded in the case report forms. Plasma will be stored at - 20 C until analysis and will be transferred to - 80 C for long term storage at HIV-NAT laboratory. Blood for pharmacokinetic study will be obtained at HIV-NAT. The TDF drug level will be determined by HPLC method at the HIV-NAT PK laboratory in Bangkok.
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Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation
Incidence and Predictor of TDF Associated Nephrotoxicity and Pharmacokinetic of TDF in HIV-1 Infected Thai Patients: A Sub-study of HIV-NAT 006 Long Term Cohort
To assess and validate equation eGFR in HIV-infected subjects and -uninfected Thai patients

With significant reductions in mortality and risk of progression to AIDS with antiretroviral therapy (ART), complications of long-standing HIV infection and treatment, including renal disease, have become increasingly important. Aging, concomitant metabolic diseases, and use of potentially nephrotoxic ART lead to higher risk for renal disease in HIV-infected persons.WHO encourage TDF as first line ARV regimen. The data on TDF related renal toxicity in Asian population is limited.

For this cohort, we plan to look at these topics:

  1. proximal tubular dysfunction between TDF and non-TDF user
  2. incidence and predictor of TDF related renal toxicity
  3. TDF plasma concentrations
  4. Pharmacokinetic of TDF when used with boosted DRV, boosted ATV, and boosted LPV in Thai population
  5. Bone density and vitamin D in patients with and without hypophosphatemia.
  6. Pharmacogenomic of TDF in Thai population
Observational Model: Cohort
Time Perspective: Cross-Sectional
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Retention:   Samples With DNA
PBMC collection
Non-Probability Sample

HIV-NAT 006 participants (TDF +non TDF)and ARV naive population

For TDF group, on TDF > 3 months HIV/HBV co-infected patients from COLD (Liver disease and HIV/HBV coinfection in the era of HAART) and TDF surveillance study

  • Renal Function
  • HIV Infection
Other: Tc99mDTPA renal clearance

Tc99mDTPA renal clearance only for 200 patients

  1. Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria
  2. serum creatinine prior and during TDF
  3. TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels
  4. stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT)
  5. serum for cystanin C ( stored sample prior taking ARV and present time)
  6. intensive 24 hours pharmacokinetic study of TDF in 20 patients
  • 1
    ARV experience (TDF based HAART)
    Intervention: Other: Tc99mDTPA renal clearance
  • 2
    ARV experience (non TDF based ART)
    Intervention: Other: Tc99mDTPA renal clearance
  • 3
    ARV Naive
    Intervention: Other: Tc99mDTPA renal clearance

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
June 2017
June 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. > 18 years old.
  2. HIV RNA < 50 copies/ml (For ART-experienced group only).

Exclusion Criteria:

  1. a history of Tc-99m DTPA allergy,
  2. malnutrition (BMI <18m2),
  3. amputation,
  4. bed-ridden,
  5. currently taking cotrimoxazole or cimetidine,
  6. acute deterioration of renal function within the last 3 months,
  7. serum creatinine > 1.5 mg/dl, or
  8. pregnant/lactating.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
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The HIV Netherlands Australia Thailand Research Collaboration
The HIV Netherlands Australia Thailand Research Collaboration
  • Chulalongkorn University
  • Kirby Institute
Principal Investigator: Praphan Phanuphak, MD, PhD HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
Principal Investigator: Kearkiat Praditpornsilpa, MD Renal division, Faculty of Medicine, Chulalongkorn University
The HIV Netherlands Australia Thailand Research Collaboration
August 2017