Plasma apolipoprotein L1 levels do not correlate with CKD.

TitlePlasma apolipoprotein L1 levels do not correlate with CKD.
Publication TypeJournal Article
Year of Publication2014
AuthorsBruggeman LA, O'Toole JF, Ross MD, Madhavan SM, Smurzynski M, Wu K, Bosch RJ, Gupta S, Pollak MR, Sedor JR, Kalayjian RC
JournalJ Am Soc Nephrol
Volume25
Issue3
Pagination634-44
Date Published2014 Mar
ISSN1533-3450
KeywordsAdult, African Americans, AIDS-Associated Nephropathy, Apolipoproteins, Case-Control Studies, Cytokines, Disease Progression, Dyslipidemias, Female, Genotype, Glomerular Filtration Rate, Humans, Lipoproteins, HDL, Longitudinal Studies, Male, Middle Aged, Phenotype, Randomized Controlled Trials as Topic, Renal Insufficiency, Chronic
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 1.73 m(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.

DOI10.1681/ASN.2013070700
Alternate JournalJ. Am. Soc. Nephrol.
PubMed ID24231663
PubMed Central IDPMC3935593
Grant ListAI036219 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
R01 MD007092 / MD / NIMHD NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
UL1 TR000439 / TR / NCATS NIH HHS / United States
UL1TR000439 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States