Associations between eGFR and albuminuria with right ventricular measures: the MESA-Right Ventricle study

Abstract

Background: Chronic kidney disease (CKD) is associated with an increased risk of pulmonary hypertension, which may lead to right ventricular (RV) pressure overload and RV dysfunction. However, the presence of subclinical changes in RV structure or function in early CKD and the influence of these changes on mortality are not well studied. We hypothesized that early CKD, as indicated by elevated albuminuria or mild reductions in estimated glomerular filtration rate (eGFR), is associated with greater RV dilation and RV mass.

Methods: We included 4063 participants (age 45-84 years) without baseline clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis. The associations of baseline creatinine-cystatin C-based eGFR and albuminuria with cardiac magnetic resonance-derived RV measures (2000-02) were examined cross-sectionally with linear regression models. Cox regression models were used to examine whether RV parameters modified the associations of eGFR and albuminuria with all-cause mortality.

Results: Participants with reductions in eGFR primarily within the 60-89 mL/min/1.73 m² category had smaller RV end-diastolic and end-systolic volumes and stroke volume (all adjusted P-trends <.001) than those with eGFR ≥90 mL/min/1.73 m², an association that was predominantly seen in participants with albuminuria below 30 mg/g creatinine. Albuminuria was more strongly associated with death among those with lower RV volumes (P-values for interaction <.03).

Conclusions: Among community-dwelling adults, reductions in eGFR primarily within the normal range were associated with smaller RV volumes and the association of albuminuria with worse survival was stronger among those with smaller RV volumes. Further studies are needed to elucidate the underlying mechanistic pathways that link kidney measures and RV morphology.

Keywords: cardiac magnetic resonance; cardiorenal syndromes; chronic kidney disease; kidney function; pulmonary hypertension.

Graphical Abstract

Figure 1:

Forest plots showing the associations of eGFR and albuminuria in KDIGO CKD categories G1–2/A1–3 with RV measures. Boxes represent effect estimates and horizontal lines represent 95% CI. Analysis includes 3763 MESA participants with a eGFR ≥60 mL/min/1.73 m². The omnibus statistics were calculated using a joint hypothesis F-test for the two contrasts of interest. The corresponding F-statistics for the omnibus tests are: 1.50 (RVEDM), 7.34 (RVEDV), 6.61 (RVESV), 9.88 (RVSV) and 1.47 (RVEF). REF = reference group (eGFR ≥90 mL/min/1.73 m² and albuminuria <30 mg/g creatinine). Model 1 is adjusted for age. Model 2 is adjusted for age, sex, ethnicity, education level, weight, height, waist circumference, diabetes, triglycerides, hypertension, angiotensin receptor blockers, ACE inhibitors, smoking (history and pack-years), total cholesterol, HDL levels, CRP, diuretic medication use, Agatston calcium score, total intentional exercise and study site. Model 3 includes all covariates used in Model 2 and is also adjusted for the analogous LV measure. RVSV was not adjusted for LV stroke volume, considering the significant inter-dependence of these measures. RV measures are non-indexed. ACE, angiotensin-converting enzyme; HDL, high-density lipoprotein.

Figure 2:

Kaplan–Meier survival curves according to albuminuria categories and non-indexed RV volumes tertiles. Kaplan–Meier survival curves show the associations of albuminuria (<30 mg/g versus ≥30 mg/g creatinine) by (A) RVEDV tertiles (log-rank P < .001), (B) RVESV tertiles (log-rank P < .001) and (C) RVSV tertiles (log-rank P < .001). RV measures are non-indexed.