Khan, Laibah Arshad

Background: Chronic kidney disease (CKD) has been linked to elevated inflammatory biomarkers, yet few studies have evaluated these associations using iothalamate-based measures of kidney function, highlighting the need for further research. Research question: Is CKD associated with elevated inflammatory markers when defined by measured glomerular filtration rate (mGFR) and urinary albumin-to-creatinine ratio (UACR)? Methods: Participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort were included if they had data available for at least one inflammatory marker at visit 2. 17 inflammatory markers were assessed, including C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), serum amyloid A, intercellular and vascular adhesion molecules (ICAM, VCAM), E-selectin, P-selectin, monocyte chemoattractant protein (MCP), myeloperoxidase (MPO), receptor for advanced glycation end products (RAGE), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2). Kindey function was assessed using the urinary clearance of iothalamate. CKD was defined as mGFR < 60 mL/min/1.73 m 2 or UACR ≥ 30 mg/g. To further assess whether associations persisted without albuminuria, we also defined CKD solely by mGFR < 60 mL/min/1.73 m 2 . Generalized estimating equations (GEE) were used to assess associations between CKD status and inflammatory markers, accounting for familial clustering. Exponentiated beta coefficients from GEE models were used to present geometric mean (GM) ratios of each biomarker by CKD status, adjusted for demographics, lifestyle factors, cardiovascular risk factors, and medication use. Results: Among 1,010 participants (mean age 61 ± 10 years; 67% women; 48% Black adults), 207 were classified as having CKD. After adjusting for potential confounders, individuals with CKD had significantly higher levels of hsCRP, VCAM, TNFR1, and TNFR2 compared to those without CKD (GM ratios > 1; p < 0.05), while the remaining inflammatory markers showed no significant differences ( Figure 1 ). Importantly, these elevations remained significant when CKD was defined by mGFR alone ( Figure 2 ). Conclusion: Our findings suggest that CKD, defined by mGFR, is associated with specific inflammatory biomarkers, underscoring the need for mechanistic studies to investigate these associations.

Background: Hypertension and systemic inflammation are independently associated with adverse cardiovascular outcomes. While hypertension is a known risk factor for left ventricular (LV) hypertrophy, the role of inflammation in LV structural changes remains unclear. It is also uncertain whether concomitant inflammation and hypertension ("inflammatory hypertension") exacerbate LV hypertrophy. Research Question: Is inflammatory hypertension associated with increased LV mass index (LVMI) compared to hypertension without inflammation? Methods: We analyzed baseline data from Black adults enrolled in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort in Jackson, Mississippi. Inflammation was defined by high sensitivity C-reactive protein (hsCRP) >3 mg/L, and hypertension as systolic blood pressure (SBP) >130 mmHg. Participants were classified into four groups: noninflammatory-normotensive (reference group), noninflammatory-hypertensive, inflammatory-normotensive, and inflammatory-hypertensive. The primary outcome was LVMI, assessed by echocardiography. Associations between groups and LVMI were evaluated using generalized estimating equations to account for familial clustering and adjusted for covariates including age, sex, education, smoking status, body mass index, number of antihypertensive medications, statin use, cholesterol, and diabetes. Results: Among 1,027 participants (mean age 64 ± 8.5 years; 71% women), baseline LVMI differed by inflammation-hypertension status. Compared with the LVMI in noninflammatory-normotensive cohort (n=108; 74.5 g/m 2 [70.4–78.6]), significantly higher LVMI was observed in noninflammatory-hypertensive (n=343; 83.6 g/m 2 [81.3–85.9], p<0.001) and inflammatory-hypertensive groups (n=497; 84.7 g/m 2 [82.8–86.7], p<0.001). There was no statistically significant difference between inflammatory-hypertensive and noninflammatory-hypertensive groups (84.7 vs 83.6 g/m 2 )(p=0.460). The inflammatory-normotensive cohort also did not differ from the reference group (74.9 g/m 2 [70.2–79.5], p=0.901). Secondary analyses using elevated IL-6 to define inflammation yielded similar findings ( Figure 1 ). Conclusion: In individuals with inflammatory hypertension, hypertension appears to be the primary driver of LV hypertrophy. Further studies in larger, diverse populations are needed to definitively evaluate the potential additive effect of inflammatory hypertension on LV remodeling.