scholarly journals Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial

2016 ◽  
Vol 27 (10) ◽  
pp. 3140-3152 ◽  
Author(s):  
Gabor Bodonyi-Kovacs ◽  
Jennie Z. Ma ◽  
Jamison Chang ◽  
Michael S. Lipkowitz ◽  
Jeffrey B. Kopp ◽  
...  
Keyword(s):  
African American ◽  
Kidney Disease ◽  
Null Allele ◽  
African American Study ◽  
Combined Effects ◽  
American Study ◽  
Ckd Progression ◽  
Risk Alleles

scholarly journals Loss of GSTM1, a NRF2 target, is associated with accelerated progression of hypertensive kidney disease in the African American Study of Kidney Disease (AASK)

2013 ◽  
Vol 304 (4) ◽  
pp. F348-F355 ◽  
Author(s):  
Jamison Chang ◽  
Jennie Z. Ma ◽  
Qing Zeng ◽  
Sylvia Cechova ◽  
Adam Gantz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
African American ◽  
Kidney Disease ◽  
Disease Progression ◽  
Genetic Variants ◽  
Null Allele ◽  
African American Study ◽  
Null Alleles ◽  
American Study ◽  
Kidney Disease Progression

Oxidative stress is acknowledged to play a role in kidney disease progression. Genetic variants that affect the capacity to handle oxidative stress may therefore influence the outcome of kidney disease. We examined whether genetic variants of the GSTM1 gene, a member of a superfamily of glutathione S-transferases, influence the course of kidney disease progression in participants of the African American Study of Kidney Disease (AASK) trial. Groups with and without the common GSTM1 null allele, GSTM1(0), differed significantly in the time to a glomerular filtration rate (GFR) event or dialysis ( P = 0.04) and in the time to GFR event, dialysis, or death ( P = 0.02). The hazard ratios (HR) for the time to a GFR event or dialysis in those with two or one null allele relative to those possessing none were 1.88 [95% confidence interval (CI), 1.07 to 3.30, P = 0.03] and 1.68 (95% CI, 1.00 to 2.84, P < 0.05), respectively. For the time to GFR event, dialysis, or death, the HR for two null alleles was 2.06 (95% CI, 1.20 to 3.55, P = 0.01) and for one null allele 1.70 (95% CI, 1.02 to 2.81, P = 0.04). We demonstrated that GSTM1 directly regulates intracellular levels of 4-hydroxynonenal (4-HNE) in vascular smooth muscle cells. Furthermore, we showed that renal 4-HNE levels and GSTM1 are both increased after reduction of renal mass (RRM) in the mouse. We conclude that GSTM1 is normally upregulated in chronic kidney disease (CKD) in a protective response to increased oxidative stress. A genetic variant that results in loss of GSTM1 activity may be deleterious in CKD.

Recruitment experience in the African American Study of Kidney disease and hypertension (AASK) pilot study

1996 ◽  
Vol 17 (4) ◽  
pp. S17-S33 ◽  
Author(s):  
Paul K. Whelton ◽  
Jeannette Y. Lee ◽  
John W. Kusek ◽  
Jeanne Charleston ◽  
Jennifer DeBruge ◽  
...  
Keyword(s):  
African American ◽  
Pilot Study ◽  
Kidney Disease ◽  
African American Study ◽  
American Study

scholarly journals Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression

2018 ◽  
Vol 29 (7) ◽  
pp. 1939-1947 ◽  
Author(s):  
Adrienne Tin ◽  
Girish Nadkarni ◽  
Anne M. Evans ◽  
Cheryl A. Winkler ◽  
Erwin Bottinger ◽  
...  
Keyword(s):  
African American ◽  
Risk Factor ◽  
Genetic Variants ◽  
Clinical Characteristics ◽  
Molecular Signature ◽  
American Study ◽  
Ckd Progression ◽  
Significance Threshold ◽  
Risk Alleles ◽  
Untargeted Profiling

Background Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles—genetic variants associated with CKD risk commonly present in persons of African descent—may reveal novel markers of CKD progression relevant to other populations.Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) (n=588; Bonferroni significance threshold P<6.5×10−5) and replicated findings in 678 black participants with CKD in BioMe, an electronic medical record–linked biobank. We tested the metabolite association with CKD progression in AASK, BioMe, and the Modification of Diet in Renal Disease (MDRD) Study.Results One metabolite, 6-bromotryptophan, was significant in AASK (P=4.7×10−5) and replicated in BioMe (P=5.7×10−3) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and BioMe participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; BioMe, 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers.Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression.

18A Reasons for joining and barriers to participation in the African-American study of kidney disease and hypertension (AASK) pilot study

1995 ◽  
Vol 16 (3) ◽  
pp. 42S ◽  
Author(s):  
John Kusek ◽  
Jeannette Lee ◽  
Jeanne Charleston ◽  
Marquetta Faulkner ◽  
Betty Levell ◽  
...  
Keyword(s):  
African American ◽  
Pilot Study ◽  
Kidney Disease ◽  
African American Study ◽  
American Study ◽  
Barriers To Participation

scholarly journals Factors associated with enrollment of African Americans into a clinical trial: Results from the African American study of kidney disease and hypertension

2008 ◽  
Vol 29 (6) ◽  
pp. 837-842 ◽  
Author(s):  
Crystal A. Gadegbeku ◽  
Phyllis Kreger Stillman ◽  
Mark D. Huffman ◽  
James S. Jackson ◽  
John W. Kusek ◽  
...  
Keyword(s):  
Clinical Trial ◽  
African American ◽  
African Americans ◽  
Kidney Disease ◽  
African American Study ◽  
American Study ◽  
Factors Associated ◽  
Clinical Trial Results
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