Pulmonary hypertension in patients with chronic kidney disease: invasive hemodynamic etiology and outcomes

Jared M O'Leary, Tufik R Assad, Meng Xu, Kelly A Birdwell, Eric Farber-Eger, Quinn S Wells, Anna R Hemnes, Evan L Brittain, Jared M O'Leary, Tufik R Assad, Meng Xu, Kelly A Birdwell, Eric Farber-Eger, Quinn S Wells, Anna R Hemnes, Evan L Brittain

Abstract

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) and associated with increased mortality but the hemodynamic profiles, clinical risk factors, and outcomes have not been well characterized. Our objective was to define the hemodynamic profile and related risk factors for PH in CKD patients. We extracted clinical and hemodynamic data from Vanderbilt's de-identified electronic medical record on all patients undergoing right heart catheterization during 1998-2014. CKD (stages III-V) was defined by estimated glomerular filtration rate thresholds. PH was defined as mean pulmonary pressure ≥ 25 mmHg and categorized into pre-capillary and post-capillary according to consensus recommendations. In total, 4635 patients underwent catheterization: 1873 (40%) had CKD; 1518 (33%) stage 3, 230 (5%) stage 4, and 125 (3%) stage 5. PH was present in 1267 (68%) of these patients. Post-capillary (n = 965, 76%) was the predominant PH phenotype among CKD patients versus 302 (24%) for pre-capillary ( P < 0.001). CKD was independently associated with pulmonary hypertension (odds ratio = 1.4, 95% confidence interval = 1.18-1.65). Mortality among CKD patients rose with worsening stage and was significantly increased by PH status. PH is common and independently associated with mortality among CKD patients referred for right heart catheterization. Post-capillary was the most common etiology of PH. These data suggest that PH is an important prognostic co-morbidity among CKD patients and that CKD itself may have a role in the development of pulmonary vascular disease in some patients.

Keywords: chronic renal insufficiency; hemodynamics; pulmonary hypertension; survival.

Figures

Fig. 1.
Fig. 1.
Flow-diagram of study population. PH, pulmonary hypertension; CKD, chronic kidney disease; RHC, right heart catheterization.
Fig. 2.
Fig. 2.
Prevalence of pulmonary hypertension by CKD stage. Bar height represents PH prevalence by CKD stage with blue bars representing pre-capillary PH (Pre-PH), orange bars representing post-capillary PH (Post-PH), and gray bars representing the total PH prevalence. The prevalence of PH increases with worsening CKD stage and the proportion of PH attributable to post-capillary PH also increases. CKD, chronic kidney disease; PH, pulmonary hypertension.
Fig. 3.
Fig. 3.
Association of clinical features with PH. Multivariate logistic regression analysis of all patients undergoing RHC. ORs for the presence of PH for all covariates. ORs and 95% CIs shown to the right. For continuous variables, effects comparing 25th and 75th percentiles were calculated. CKD and African American status were independently associated with PH, along with known PH risk factors congestive heart failure, Scleroderma, COPD, RAP, and BNP.
Fig. 4.
Fig. 4.
Survival according to CKD and PH status. (a) Kaplan–Meyer curves of unadjusted mortality in years based on the presence or absence of PH and any degree of CKD. The number at risk is displayed beneath the curves. (b) Kaplan–Meyer curves of unadjusted mortality in years among PH patients based on the presence or absence of CKD III or CKD IV/V. The number at risk is displayed beneath the curves. Adjusted HRs and 95% CIs for CKD stages III–V are shown in the box. Full multivariate analysis with all covariates displayed in Fig. 5.
Fig. 5.
Fig. 5.
Adjusted HRs for mortality. Multivariate regression analysis of all patients undergoing RHC. HRs for mortality for all covariates in the multivariate regression. HR and 95% CIs shown to the right. For continuous variables, effects comparing 25th and 75th percentiles were calculated. After adjustment for clinical values, CKD stage has a strong association with increased mortality, along with age, male sex, COPD, interstitial lung disease, and mPAP.
Fig. 6.
Fig. 6.
Survival by pre-capillary or post-capillary PH status among CKD patients. Kaplan–Meyer curves of unadjusted mortality in years among CKD patients based on pre-capillary vs. post-capillary PH status. There was no difference in mortality between groups. Pre-PH, pre-capillary PH; Post-PH, post-capillary PH.

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