Skip to main content
Top
Published in: Infection 5/2016

01-10-2016 | Original Paper

Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate

Authors: A. J. Zeder, R. Hilge, S. Schrader, J. R. Bogner, U. Seybold

Published in: Infection | Issue 5/2016

Login to get access

Abstract

Objectives

The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100–500 mg/g creatinine) among HIV-positive adults.

Methods

Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed.

Results

Among 411 patients, 18 (4.4 %) presented albuminuria >300 mg/g creatinine and/or proteinuria >500 mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1 %) had no significant proteinuria or albuminuria (<100 and <30 mg/g creatinine, respectively), 60 (15.3 %) had moderate albuminuria, while 152 (38.7 %) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir <500/µl, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR).

Conclusions

We detected significant proteinuria in 230 (56.0 %) of 411 HIV-positive patients. Among this group, 152 (66.1 %) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed.
Literature
1.
go back to reference Wada N, Jacobson LP, Cohen M, French A, Phair J, Munoz A. Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed simultaneously in long-term cohort studies, 1984–2008. Am J Epidemiol. 2013;177:116–25.CrossRefPubMedPubMedCentral Wada N, Jacobson LP, Cohen M, French A, Phair J, Munoz A. Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed simultaneously in long-term cohort studies, 1984–2008. Am J Epidemiol. 2013;177:116–25.CrossRefPubMedPubMedCentral
2.
go back to reference Selik RM, Byers RH Jr, Dworkin MS. Trends in diseases reported on US death certificates that mentioned HIV infection, 1987–1999. J Acquir Immune Defic Syndr. 2002;29:378–87.CrossRefPubMed Selik RM, Byers RH Jr, Dworkin MS. Trends in diseases reported on US death certificates that mentioned HIV infection, 1987–1999. J Acquir Immune Defic Syndr. 2002;29:378–87.CrossRefPubMed
4.
go back to reference Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. J Infect Dis. 2008;197:1548–57.CrossRefPubMedPubMedCentral Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. J Infect Dis. 2008;197:1548–57.CrossRefPubMedPubMedCentral
5.
go back to reference Shahinian V, Rajaraman S, Borucki M, Grady J, Hollander WM, Ahuja TS. Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients. Am J Kidney Dis. 2000;35:884–8.CrossRefPubMed Shahinian V, Rajaraman S, Borucki M, Grady J, Hollander WM, Ahuja TS. Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients. Am J Kidney Dis. 2000;35:884–8.CrossRefPubMed
6.
go back to reference Jao J, Wyatt CM. Antiretroviral medications: adverse effects on the kidney. Adv Chronic Kidney Dis. 2010;17:72–82.CrossRefPubMed Jao J, Wyatt CM. Antiretroviral medications: adverse effects on the kidney. Adv Chronic Kidney Dis. 2010;17:72–82.CrossRefPubMed
7.
go back to reference Anderson PL, Lichtenstein KA, Gerig NE, Kiser JJ, Bushman LR. Atazanavir-containing renal calculi in an HIV-infected patient. AIDS. 2007;21:1060–2.CrossRefPubMed Anderson PL, Lichtenstein KA, Gerig NE, Kiser JJ, Bushman LR. Atazanavir-containing renal calculi in an HIV-infected patient. AIDS. 2007;21:1060–2.CrossRefPubMed
8.
go back to reference Green ST, McKendrick MW, Schmid ML, Mohsen AH, Prakasam SF. Renal calculi developing de novo in a patient taking saquinavir. Int J STD AIDS. 1998;9:555.CrossRefPubMed Green ST, McKendrick MW, Schmid ML, Mohsen AH, Prakasam SF. Renal calculi developing de novo in a patient taking saquinavir. Int J STD AIDS. 1998;9:555.CrossRefPubMed
9.
go back to reference Roling J, Schmid H, Fischereder M, Draenert R, Goebel FD. HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy. Clin Infect Dis. 2006;42:1488–95.CrossRefPubMed Roling J, Schmid H, Fischereder M, Draenert R, Goebel FD. HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy. Clin Infect Dis. 2006;42:1488–95.CrossRefPubMed
10.
go back to reference Wyatt CM, Hoover DR, Shi Q, Seaberg E, Wei C, Tien PC, et al. Microalbuminuria is associated with all-cause and AIDS mortality in women with HIV infection. J Acquir Immune Defic Syndr. 2010;55:73–7.CrossRefPubMedPubMedCentral Wyatt CM, Hoover DR, Shi Q, Seaberg E, Wei C, Tien PC, et al. Microalbuminuria is associated with all-cause and AIDS mortality in women with HIV infection. J Acquir Immune Defic Syndr. 2010;55:73–7.CrossRefPubMedPubMedCentral
11.
go back to reference Szczech LA, Hoover DR, Feldman JG, Cohen MH, Gange SJ, Gooze L, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis. 2004;39:1199–206.CrossRefPubMed Szczech LA, Hoover DR, Feldman JG, Cohen MH, Gange SJ, Gooze L, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis. 2004;39:1199–206.CrossRefPubMed
12.
go back to reference Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med. 2004;43:9–17.CrossRefPubMed Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med. 2004;43:9–17.CrossRefPubMed
13.
go back to reference Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation. 2010;121:651–8.CrossRefPubMedPubMedCentral Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation. 2010;121:651–8.CrossRefPubMedPubMedCentral
14.
go back to reference Hadigan C, Edwards E, Rosenberg A, Purdy JB, Fleischman E, Howard L, et al. Microalbuminuria in HIV disease. Am J Nephrol. 2013;37:443–51.CrossRefPubMed Hadigan C, Edwards E, Rosenberg A, Purdy JB, Fleischman E, Howard L, et al. Microalbuminuria in HIV disease. Am J Nephrol. 2013;37:443–51.CrossRefPubMed
16.
go back to reference National Kidney Foundation Kidney Disease Outcomes Quality Initiative. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3.
17.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentral
18.
go back to reference Hosmer DW, Jovanovic B, Lemeshow S. Best subsets logistic regression. Biometrics. 1989;45:1265–70.CrossRef Hosmer DW, Jovanovic B, Lemeshow S. Best subsets logistic regression. Biometrics. 1989;45:1265–70.CrossRef
19.
go back to reference Gupta SK, Kitch D, Tierney C, Melbourne K, Ha B, McComsey GA. Markers of renal disease and function are associated with systemic inflammation in HIV infection. HIV Med. 2015. Gupta SK, Kitch D, Tierney C, Melbourne K, Ha B, McComsey GA. Markers of renal disease and function are associated with systemic inflammation in HIV infection. HIV Med. 2015.
20.
go back to reference Estrella MM, Parekh RS, Astor BC, Bolan R, Evans RW, Palella FJ Jr, et al. Chronic kidney disease and estimates of kidney function in HIV infection: a cross-sectional study in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr. 2011;57:380–6.CrossRefPubMedPubMedCentral Estrella MM, Parekh RS, Astor BC, Bolan R, Evans RW, Palella FJ Jr, et al. Chronic kidney disease and estimates of kidney function in HIV infection: a cross-sectional study in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr. 2011;57:380–6.CrossRefPubMedPubMedCentral
21.
go back to reference Reynes J, Cournil A, Peyriere H, Psomas C, Guiller E, Chatron M, et al. Tubular and glomerular proteinuria in HIV-infected adults with estimated glomerular filtration rate >/= 60 ml/min per 1.73 m2. AIDS. 2013;27:1295–302.CrossRefPubMed Reynes J, Cournil A, Peyriere H, Psomas C, Guiller E, Chatron M, et al. Tubular and glomerular proteinuria in HIV-infected adults with estimated glomerular filtration rate >/= 60 ml/min per 1.73 m2. AIDS. 2013;27:1295–302.CrossRefPubMed
22.
go back to reference Gravemann S, Brinkkoetter PT, Vehreschild JJ, Franke B, Ehren K, Bunemann E et al. Low-grade proteinuria is highly prevalent in HIV-positive patients on antiretroviral treatment. AIDS. 2014. Gravemann S, Brinkkoetter PT, Vehreschild JJ, Franke B, Ehren K, Bunemann E et al. Low-grade proteinuria is highly prevalent in HIV-positive patients on antiretroviral treatment. AIDS. 2014.
23.
go back to reference Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010;9:545–59.CrossRefPubMed Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010;9:545–59.CrossRefPubMed
24.
go back to reference Purswani M, Patel K, Kopp JB, Seage GR 3rd, Chernoff MC, Hazra R, et al. Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection. Pediatr Infect Dis J. 2013;32:495–500.CrossRefPubMedPubMedCentral Purswani M, Patel K, Kopp JB, Seage GR 3rd, Chernoff MC, Hazra R, et al. Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection. Pediatr Infect Dis J. 2013;32:495–500.CrossRefPubMedPubMedCentral
25.
go back to reference Scherzer R, Estrella M, Li Y, Choi AI, Deeks SG, Grunfeld C, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012;26:867–75.CrossRefPubMedPubMedCentral Scherzer R, Estrella M, Li Y, Choi AI, Deeks SG, Grunfeld C, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012;26:867–75.CrossRefPubMedPubMedCentral
26.
go back to reference Kelly MD, Gibson A, Bartlett H, Rowling D, Patten J. Tenofovir associated proteinuria. AIDS. 2012. Kelly MD, Gibson A, Bartlett H, Rowling D, Patten J. Tenofovir associated proteinuria. AIDS. 2012.
27.
go back to reference Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773–80.CrossRefPubMed Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773–80.CrossRefPubMed
28.
go back to reference Bickel M, Khaykin P, Stephan C, Schmidt K, Buettner M, Amann K, et al. Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration. HIV Med. 2013;14:633–8.CrossRefPubMed Bickel M, Khaykin P, Stephan C, Schmidt K, Buettner M, Amann K, et al. Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration. HIV Med. 2013;14:633–8.CrossRefPubMed
29.
go back to reference Woodward CL, Hall AM, Williams IG, Madge S, Copas A, Nair D, et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009;10:482–7.CrossRefPubMed Woodward CL, Hall AM, Williams IG, Madge S, Copas A, Nair D, et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009;10:482–7.CrossRefPubMed
30.
31.
go back to reference Szczech LA, Menezes P, Byrd Quinlivan E, van der Horst C, Bartlett JA, Svetkey LP. Microalbuminuria predicts overt proteinuria among patients with HIV infection. HIV Med. 2010;11:419–26.PubMedPubMedCentral Szczech LA, Menezes P, Byrd Quinlivan E, van der Horst C, Bartlett JA, Svetkey LP. Microalbuminuria predicts overt proteinuria among patients with HIV infection. HIV Med. 2010;11:419–26.PubMedPubMedCentral
32.
go back to reference Franceschini N, Napravnik S, Eron JJ Jr, Szczech LA, Finn WF. Incidence and etiology of acute renal failure among ambulatory HIV-infected patients. Kidney Int. 2005;67:1526–31.CrossRefPubMed Franceschini N, Napravnik S, Eron JJ Jr, Szczech LA, Finn WF. Incidence and etiology of acute renal failure among ambulatory HIV-infected patients. Kidney Int. 2005;67:1526–31.CrossRefPubMed
33.
go back to reference Wyatt CM, Rosenstiel PE, Klotman PE. HIV-associated nephropathy. Contrib Nephrol. 2008;159:151–61.CrossRefPubMed Wyatt CM, Rosenstiel PE, Klotman PE. HIV-associated nephropathy. Contrib Nephrol. 2008;159:151–61.CrossRefPubMed
34.
go back to reference Insight start study group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015. Insight start study group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015.
35.
go back to reference Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–52.CrossRefPubMed Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–52.CrossRefPubMed
36.
go back to reference Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72.CrossRefPubMed Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72.CrossRefPubMed
Metadata
Title
Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate
Authors
A. J. Zeder
R. Hilge
S. Schrader
J. R. Bogner
U. Seybold
Publication date
01-10-2016
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 5/2016
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-016-0911-1

Other articles of this Issue 5/2016

Infection 5/2016 Go to the issue