This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension.
AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan.
Carriers of high-risk APOL1 variants (n = 1370; 12.3%) had higher prevalence of hypertension, use of cholesterol-lowering medications, and reduced estimated glomerular filtration rate (eGFR).
APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV.
Associations of race and APOL1 genotypes with blood pressure change, separately, using linear mixed-effects and multinomial logistic regression models, adjusting for demographic, socioeconomic, and traditional hypertension risk factors, anti-hypertensive medication use, and kidney function were evaluated.
APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [p<sub>com</sub>] = 1.9 × 10<sup>-5</sup>).
The major focus of this commentary on providing understanding about the <i>apolipoprotein 1</i> (<i>APOL1</i>) gene, the protein encoded by this gene (apoL1) and the mechanistic details regarding the role of apoL1 in the lysis of <i>Trypanosoma brucei</i> Information about <i>APOL1</i> genetic variants, <i>APOL1G1</i> and <i>APOL1G2</i>, is provided along with the association of these variants with hypertension-attributed end-stage renal disease (ESRD) and focal segmental glomerulosclerosis (FSGS).
Case and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use.
Our study was a longitudinal observational study of 622 participants in the African American Study of Kidney Disease and Hypertension with APOL1 genotyping and sufficient follow-up for estimating GFR trajectories.
Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility.
In conclusion, GSTM1 null and APOL1 high-risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high-risk genotypes had highest risk of adverse renal outcomes.
We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality).
In 221 patients with sickle cell disease at the University of Illinois at Chicago, we replicated the finding of an association of APOL1 G1/G2 with proteinuria, specifically with urine albumin concentration (β=1.1, P=0.003), observed an even stronger association with hemoglobinuria (OR=2.5, P=4.3×10(-6)), and also replicated the finding of an association with hemoglobinuria in 487 patients from the Walk-Treatment of Pulmonary Hypertension and Sickle cell Disease with Sildenafil Therapy study (OR=2.6, P=0.003).
The effects of nephropathy risk variants in the apolipoprotein L1 gene (APOL1) on renal histopathology in African Americans with arterionephrosclerosis or putative 'hypertension-associated' nephropathy are unknown.
Forty of the 61 cases (66 %) with a family history of kidney disease had two APOL1 risk variants, significantly higher than the prevalence in controls and the general African American population (p < 0.001); 24 of 29 patients with hypertension-attributed kidney disease had two APOL1 risk variants, while none of nine hypertensive patients without kidney disease had more than one risk allele.
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).
Associations between mass scores and APOL1 were assessed adjusting for age, gender, African ancestry, body mass index (BMI), hemoglobin A1c, smoking, hypertension, use of statins and angiotensin-converting enzyme inhibitors, albuminuria, and eGFR.
The findings mandate urgency in clarifying mechanisms whereby APOL1 region risk variants interact with environmental triggers to cause progressive kidney disease accompanied by dangerous hypertension.
The definition of APOL1 nephropathy also confirms the long-held assumption by many clinicians that kidney disease attributed to hypertension in African populations represents an underlying glomerulopathy.
Nevertheless, not all African Americans with hypertension who progress to end-stage kidney disease have two APOL1 risk variants, and individuals of European and Asian descent also manifest arterionephrosclerosis.
To better understand this, coding variants in the apolipoprotein L1 (APOL1) and the nonmuscle myosin heavy chain 9 (MYH9) genes were evaluated for an association with hypertension-attributed nephropathy and clinical outcomes in a case-control study.
The world's highest frequencies of APOL1 risk alleles have been reported in West African nations, overlapping regions with a high incidence of CKD and hypertension.