BACKGROUND AND OBJECTIVES: Common apolipoprotein L1 (APOL1) variants are associated with increased risk of progressive CKD; however, not all individuals with high-risk APOL1 variants experience CKD progression. Identification of factors contributing to heterogeneity has important scientific and clinical implications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable Cox models, we analyzed data from 693 participants in the African American Study of Kidney Disease and Hypertension to identify factors that modify the association between APOL1 genotypes and CKD progression (doubling of serum creatinine or incident ESRD). RESULTS:Participant mean age was 54 years old, median GFR was 49 ml/min per 1.73 m(2), and 23% had the APOL1 high-risk genotype (two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288 (42%) participants experienced CKD progression. As previously reported, the high-risk genotype was associated with higher risk of CKD progression compared with the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI], 1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI, 1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index ≥ 30 versus <30 kg/m(2); P interaction =0.04) and increased urinary excretion of urea nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30 for urine urea nitrogen ≥ 8 versus <8 g/d; P interaction =0.04) were associated with lower APOL1-associated risk for CKD progression, these findings were not robust in sensitivity analyses with alternative cut points. No other sociodemographic (e.g., education and income), clinical (e.g., systolic BP and smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or fibroblast growth factor 23) variables modified the association between APOL1 and CKD progression (P interaction >0.05 for each). CONCLUSIONS: Sociodemographic factors and common risk factors for CKD progression do not seem to alter APOL1-related CKD progression. Additional investigation is needed to identify nontraditional factors that may affect the association between APOL1 and progressive CKD.
RCT Entities:
BACKGROUND AND OBJECTIVES: Common apolipoprotein L1 (APOL1) variants are associated with increased risk of progressive CKD; however, not all individuals with high-risk APOL1 variants experience CKD progression. Identification of factors contributing to heterogeneity has important scientific and clinical implications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable Cox models, we analyzed data from 693 participants in the African American Study of Kidney Disease and Hypertension to identify factors that modify the association between APOL1 genotypes and CKD progression (doubling of serum creatinine or incident ESRD). RESULTS:Participant mean age was 54 years old, median GFR was 49 ml/min per 1.73 m(2), and 23% had the APOL1 high-risk genotype (two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288 (42%) participants experienced CKD progression. As previously reported, the high-risk genotype was associated with higher risk of CKD progression compared with the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI], 1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI, 1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index ≥ 30 versus <30 kg/m(2); P interaction =0.04) and increased urinary excretion of urea nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30 for urine urea nitrogen ≥ 8 versus <8 g/d; P interaction =0.04) were associated with lower APOL1-associated risk for CKD progression, these findings were not robust in sensitivity analyses with alternative cut points. No other sociodemographic (e.g., education and income), clinical (e.g., systolic BP and smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or fibroblast growth factor 23) variables modified the association between APOL1 and CKD progression (P interaction >0.05 for each). CONCLUSIONS: Sociodemographic factors and common risk factors for CKD progression do not seem to alter APOL1-related CKD progression. Additional investigation is needed to identify nontraditional factors that may affect the association between APOL1 and progressive CKD.
Authors: J Kosacka; M Kern; N Klöting; S Paeschke; A Rudich; Y Haim; M Gericke; H Serke; M Stumvoll; I Bechmann; M Nowicki; M Blüher Journal: Mol Cell Endocrinol Date: 2015-03-26 Impact factor: 4.102
Authors: Barry I Freedman; Jeffrey B Kopp; Carl D Langefeld; Giulio Genovese; David J Friedman; George W Nelson; Cheryl A Winkler; Donald W Bowden; Martin R Pollak Journal: J Am Soc Nephrol Date: 2010-08-05 Impact factor: 10.121
Authors: Robert C Kalayjian; Bryan Lau; Rhoderick N Mechekano; Heidi M Crane; Benigno Rodriguez; Robert A Salata; Zipporah Krishnasami; James H Willig; Jeffrey N Martin; Richard D Moore; Joseph J Eron; Mari M Kitahata Journal: AIDS Date: 2012-09-24 Impact factor: 4.177
Authors: Adrienne Tin; Morgan E Grams; Nisa M Maruthur; Brad C Astor; David Couper; Thomas H Mosley; Myriam Fornage; Rulan S Parekh; Josef Coresh; Wen Hong Linda Kao Journal: Clin J Am Soc Nephrol Date: 2015-04-17 Impact factor: 8.237
Authors: Jeffrey B Kopp; George W Nelson; Karmini Sampath; Randall C Johnson; Giulio Genovese; Ping An; David Friedman; William Briggs; Richard Dart; Stephen Korbet; Michele H Mokrzycki; Paul L Kimmel; Sophie Limou; Tejinder S Ahuja; Jeffrey S Berns; Justyna Fryc; Eric E Simon; Michael C Smith; Howard Trachtman; Donna M Michel; Jeffrey R Schelling; David Vlahov; Martin Pollak; Cheryl A Winkler Journal: J Am Soc Nephrol Date: 2011-10-13 Impact factor: 10.121
Authors: Michelle M Estrella; Man Li; Adrienne Tin; Alison G Abraham; Michael G Shlipak; Sudhir Penugonda; Shehnaz K Hussain; Frank J Palella; Steven M Wolinsky; Jeremy J Martinson; Rulan S Parekh; W H Linda Kao Journal: Clin Infect Dis Date: 2014-10-03 Impact factor: 9.079
Authors: Hanghang Wang; Patrick H Pun; Lydia Kwee; Damian Craig; Carol Haynes; Megan Chryst-Ladd; Laura P Svetkey; Uptal D Patel; Elizabeth R Hauser; Martin R Pollak; William E Kraus; Svati H Shah Journal: Cardiorenal Med Date: 2016-12-29 Impact factor: 2.041
Authors: Elaine Ku; Michael S Lipkowitz; Lawrence J Appel; Afshin Parsa; Jennifer Gassman; David V Glidden; Miroslaw Smogorzewski; Chi-Yuan Hsu Journal: Kidney Int Date: 2016-12-04 Impact factor: 10.612
Authors: Deidra C Crews; Tanushree Banerjee; Donald E Wesson; Hal Morgenstern; Rajiv Saran; Nilka Ríos Burrows; Desmond E Williams; Neil R Powe Journal: Am J Nephrol Date: 2018-03-09 Impact factor: 3.754
Authors: Adrienne Tin; Morgan E Grams; Michelle Estrella; Michael Lipkowitz; Tom H Greene; Wen Hong Linda Kao; Liang Li; Lawrence J Appel Journal: Clin J Am Soc Nephrol Date: 2016-05-26 Impact factor: 8.237
Authors: Robert E Olivo; Clemontina A Davenport; Clarissa J Diamantidis; Nrupen A Bhavsar; Crystal C Tyson; Rasheeda Hall; Aurelian Bidulescu; Bessie Young; Stanford E Mwasongwe; Jane Pendergast; L Ebony Boulware; Julia J Scialla Journal: Nephrol Dial Transplant Date: 2018-06-01 Impact factor: 5.992
Authors: Teresa K Chen; Adrienne Tin; Carmen A Peralta; Lawrence J Appel; Michael J Choi; Michael S Lipkowitz; Cheryl A Winkler; Michelle M Estrella Journal: Clin J Am Soc Nephrol Date: 2017-10-19 Impact factor: 8.237
Authors: Jenny Wei; Kirsten L Johansen; Charles E McCulloch; Michael Lipkowitz; Matthew Weir; Feng Lin; Vito M Campese; Miroslaw Smogorzewski; Elaine Ku Journal: Am J Kidney Dis Date: 2019-12-16 Impact factor: 8.860