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

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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.

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References

  1. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. Medapalli RK, He JC, Klotman PE. HIV-associated nephropathy: pathogenesis. Curr Opin Nephrol Hypertens. 2011;20:306–11.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Jao J, Wyatt CM. Antiretroviral medications: adverse effects on the kidney. Adv Chronic Kidney Dis. 2010;17:72–82.

    Article  PubMed  Google Scholar 

  7. Anderson PL, Lichtenstein KA, Gerig NE, Kiser JJ, Bushman LR. Atazanavir-containing renal calculi in an HIV-infected patient. AIDS. 2007;21:1060–2.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. Nangaku M. Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med. 2004;43:9–17.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. European AIDS Clinical Society. EACS Guidelines—Version 8.0. European AIDS Clinical Society. 2015. http://www.eacsociety.org/files/2015_eacsguidelines_8.0-english_revised-20151104.pdf. Accessed 22 Nov 2015.

  16. 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. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hosmer DW, Jovanovic B, Lemeshow S. Best subsets logistic regression. Biometrics. 1989;45:1265–70.

    Article  Google Scholar 

  19. 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. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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. Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010;9:545–59.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kelly MD, Gibson A, Bartlett H, Rowling D, Patten J. Tenofovir associated proteinuria. AIDS. 2012.

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. Szczech LA, Grunfeld C, Scherzer R, Canchola JA, van der Horst C, Sidney S, et al. Microalbuminuria in HIV infection. AIDS. 2007;21:1003–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. Wyatt CM, Rosenstiel PE, Klotman PE. HIV-associated nephropathy. Contrib Nephrol. 2008;159:151–61.

    Article  CAS  PubMed  Google Scholar 

  34. Insight start study group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015.

  35. 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.

    Article  PubMed  Google Scholar 

  36. 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.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank all the physicians and staff of our outpatient clinic for their help in data collection and support of the study. Data management for this study was supported by Deutsches Zentrum für Infektionsforschung (DZIF) Grant Number TI 02.001.

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Correspondence to A. J. Zeder.

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Conflict of interest

Robert Hilge and Svenja Schrader declare no conflicts of interest. Andreas J. Zeder has received a travel grant and congress sponsoring from Janssen. Johannes R. Bogner has reveived honoraria for lectures from AbbVie, Boehringer Ingelheim, Gilead, MSD, Janssen and ViiV. Ulrich Seybold has received travel and conference support from Boehringer Ingelheim, Gilead and ViiV and has received honoraria for lectures and educational material from Gilead and Janssen and has carried out advisory board and speakers’ bureau activity for Gilead, MSD and ViiV.

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Zeder, A.J., Hilge, R., Schrader, S. et al. Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate. Infection 44, 641–649 (2016). https://doi.org/10.1007/s15010-016-0911-1

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  • DOI: https://doi.org/10.1007/s15010-016-0911-1

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