The Utility of Kidney Injury Molecule-1 As an Early Biomarker of Kidney Injury in People Living with HIV

Overview

Journal Int J STD AIDS

Specialty Infectious Diseases

Date 2020 Sep 21

PMID 32951563

Authors

Mohammed I Danjuma

Shaikha Al Shokri

Nadia Bakhsh

Mohammed A Alamin

Mohamed Gh Mohamedali

Igbiks Tamuno

Affiliations

Soon will be listed here.

Abstract

There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve ( =104) or treatment experienced ( =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68-0.98, P = 0.02; odds ratio 8.9, CI 1.6-48.6, p = 0.01; and odds ratio 0.05, CI 0.03-0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.

References

Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A . Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009; 54(6):1012-24. DOI: 10.1053/j.ajkd.2009.07.020. View

Pushpakom S, Liptrott N, Rodriguez-Novoa S, Labarga P, Soriano V, Albalater M . Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011; 204(1):145-53. PMC: 3105036. DOI: 10.1093/infdis/jir215. View

Szczech L, Grunfeld C, Scherzer R, Canchola J, van der Horst C, Sidney S . Microalbuminuria in HIV infection. AIDS. 2007; 21(8):1003-9. PMC: 3189480. DOI: 10.1097/QAD.0b013e3280d3587f. View

Peralta C, Scherzer R, Grunfeld C, ABraham A, Tien P, Devarajan P . Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). HIV Med. 2013; 15(5):291-300. PMC: 3975680. DOI: 10.1111/hiv.12113. View

Chaturvedi S, Farmer T, Kapke G . Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci. 2009; 5(2):128-34. PMC: 2631222. DOI: 10.7150/ijbs.5.128. View

Gallant J, DeJesus E, Arribas J, Pozniak A, Gazzard B, Campo R . Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006; 354(3):251-60. DOI: 10.1056/NEJMoa051871. View

Burton J, Goldsmith D, Ruddock N, Shroff R, Wan M . Renal association commentary on the KDIGO (2017) clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD. BMC Nephrol. 2018; 19(1):240. PMC: 6149202. DOI: 10.1186/s12882-018-1037-8. View

Han W, Bailly V, Abichandani R, Thadhani R, Bonventre J . Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002; 62(1):237-44. DOI: 10.1046/j.1523-1755.2002.00433.x. View

Winston J, Bruggeman L, Ross M, Jacobson J, Ross L, DAgati V . Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med. 2001; 344(26):1979-84. DOI: 10.1056/NEJM200106283442604. View

10.

Post F, Moyle G, Stellbrink H, Domingo P, Podzamczer D, Fisher M . Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010; 55(1):49-57. DOI: 10.1097/QAI.0b013e3181dd911e. View

11.

Kjeldsen L, Johnsen A, Sengelov H, Borregaard N . Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993; 268(14):10425-32. View

12.

Izzedine H, Hulot J, Villard E, Goyenvalle C, Dominguez S, Ghosn J . Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J Infect Dis. 2006; 194(11):1481-91. DOI: 10.1086/508546. View

13.

Chazot R, Botelho-Nevers E, Fresard A, Maillard N, Mariat C, Lucht F . Diagnostic challenges of kidney diseases in HIV-infected patients. Expert Rev Anti Infect Ther. 2017; 15(10):903-915. DOI: 10.1080/14787210.2017.1379395. View

14.

Ryom L, Mocroft A, Kirk O, Worm S, Kamara D, Reiss P . Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis. 2013; 207(9):1359-69. PMC: 3610424. DOI: 10.1093/infdis/jit043. View

15.

Kamijo-Ikemori A, Sugaya T, Yasuda T, Kawata T, Ota A, Tatsunami S . Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients. Diabetes Care. 2011; 34(3):691-6. PMC: 3041209. DOI: 10.2337/dc10-1392. View

16.

Wagener G, Jan M, Kim M, Mori K, Barasch J, Sladen R . Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006; 105(3):485-91. DOI: 10.1097/00000542-200609000-00011. View

17.

Bruggeman L, Ross M, Tanji N, Cara A, Dikman S, Gordon R . Renal epithelium is a previously unrecognized site of HIV-1 infection. J Am Soc Nephrol. 2000; 11(11):2079-2087. DOI: 10.1681/ASN.V11112079. View

18.

Jotwani V, Scherzer R, Abraham A, Estrella M, Bennett M, Cohen M . Association of urine α1-microglobulin with kidney function decline and mortality in HIV-infected women. Clin J Am Soc Nephrol. 2014; 10(1):63-73. PMC: 4284407. DOI: 10.2215/CJN.03220314. View

19.

Ascher S, Scherzer R, Estrella M, Shlipak M, Ng D, Palella F . Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men. Am J Nephrol. 2019; 50(5):401-410. PMC: 6856405. DOI: 10.1159/000502898. View

20.

Jose S, Nelson M, Phillips A, Chadwick D, Trevelion R, Jones R . Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir. AIDS. 2017; 31(4):485-492. PMC: 5278893. DOI: 10.1097/QAD.0000000000001353. View