title: Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients.
abstract: BACKGROUND
  Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients.
  
  
  METHODS
  In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI).
  
  
  RESULTS
  Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR.
  
  
  CONCLUSIONS
  In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.
authors.affiliation: Academic Department of Renal Sciences, King's College London, London, United Kingdom.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Campbell
authors.forename: Tracy
authors.initials: T
authors.lastname: Dew
authors.forename: Rashim
authors.initials: R
authors.lastname: Salota
authors.forename: Emily
authors.initials: E
authors.lastname: Cheserem
authors.forename: Lisa
authors.initials: L
authors.lastname: Hamzah
authors.forename: Fowzia
authors.initials: F
authors.lastname: Ibrahim
authors.forename: Pantelis A
authors.initials: PA
authors.lastname: Sarafidis
authors.forename: Caje F
authors.initials: CF
authors.lastname: Moniz
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Hendry
authors.forename: Mary
authors.initials: M
authors.lastname: Poulton
authors.forename: Roy A
authors.initials: RA
authors.lastname: Sherwood
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000652:urine; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000652:urine*; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000652:urine*; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D011507:Proteinuria / Q000175:diagnosis / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000652:urine*; D054840:Retinol-Binding Proteins, Cellular / Q000652:urine*; D012709:Serum Albumin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D054840:Retinol-Binding Proteins, Cellular; D012709:Serum Albumin