Plasma apolipoprotein L1 levels do not correlate with CKD

Leslie A. Bruggeman, John F. O'Toole, Michael D. Ross, Sethu M. Madhavan, Marlene Smurzynski, Kunling Wu, Ronald J. Bosch, Samir Gupta, Martin R. Pollak, John R. Sedor, Robert C. Kalayjian

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Abstract

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73m 2 (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.

Original languageEnglish
Pages (from-to)634-644
Number of pages11
JournalJournal of the American Society of Nephrology
Volume25
Issue number3
DOIs
StatePublished - Mar 2014

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Apolipoproteins
Proteinuria
Genotype
HIV
Cytokines
African Americans
Kidney
Kidney Diseases
Dyslipidemias
LDL Cholesterol
Observational Studies
Case-Control Studies
Fasting
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Bruggeman, L. A., O'Toole, J. F., Ross, M. D., Madhavan, S. M., Smurzynski, M., Wu, K., ... Kalayjian, R. C. (2014). Plasma apolipoprotein L1 levels do not correlate with CKD. Journal of the American Society of Nephrology, 25(3), 634-644. https://doi.org/10.1681/ASN.2013070700

Plasma apolipoprotein L1 levels do not correlate with CKD. / Bruggeman, Leslie A.; O'Toole, John F.; Ross, Michael D.; Madhavan, Sethu M.; Smurzynski, Marlene; Wu, Kunling; Bosch, Ronald J.; Gupta, Samir; Pollak, Martin R.; Sedor, John R.; Kalayjian, Robert C.

In: Journal of the American Society of Nephrology, Vol. 25, No. 3, 03.2014, p. 634-644.

Research output: Contribution to journalArticle

Bruggeman, LA, O'Toole, JF, Ross, MD, Madhavan, SM, Smurzynski, M, Wu, K, Bosch, RJ, Gupta, S, Pollak, MR, Sedor, JR & Kalayjian, RC 2014, 'Plasma apolipoprotein L1 levels do not correlate with CKD', Journal of the American Society of Nephrology, vol. 25, no. 3, pp. 634-644. https://doi.org/10.1681/ASN.2013070700
Bruggeman LA, O'Toole JF, Ross MD, Madhavan SM, Smurzynski M, Wu K et al. Plasma apolipoprotein L1 levels do not correlate with CKD. Journal of the American Society of Nephrology. 2014 Mar;25(3):634-644. https://doi.org/10.1681/ASN.2013070700
Bruggeman, Leslie A. ; O'Toole, John F. ; Ross, Michael D. ; Madhavan, Sethu M. ; Smurzynski, Marlene ; Wu, Kunling ; Bosch, Ronald J. ; Gupta, Samir ; Pollak, Martin R. ; Sedor, John R. ; Kalayjian, Robert C. / Plasma apolipoprotein L1 levels do not correlate with CKD. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 3. pp. 634-644.
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