Abstract P331: Association of Extraosseous Calcification With Pulmonary Hypertension in Patients Evaluated for Kidney Transplantation
Authors: Caughey Melissa C , Puri Aditi , Detwiler Randal K , Kshirsagar Abhijit V , Ford Hubert J , Rose-Jones Lisa J , Hinderliter Alan L 
Published: July 2021

Background:
Pulmonary hypertension (PH) is commonly reported in patients with end-stage renal disease (ESRD), and is associated with early graft failure and death in kidney transplant recipients. Calcifications of the lung, pulmonary vessels, heart, and kidney are frequently observed with ESRD, the consequence of secondary hyperparathyroidism. It follows that pulmonary artery vasculopathy, notably from extraosseous calcification, may contribute to PH. A popular, but unestablished, theory is that the stiffened pulmonary artery is unable to accommodate elevations in right ventricular stroke volume caused by arteriovenous (AV) hemodialysis shunts. We hypothesized that extraosseous calcification is related to PH in patients evaluated for kidney transplantation, and that the association is largely driven by AV shunts.

Methods:
Established in 2006, the UNC Cardiorenal Registry offers ongoing enrollment to all patients with stage 4 or 5 chronic kidney disease (CKD) referred for pretransplant cardiac evaluation. Pulmonary artery systolic pressure (PASP) was derived from routine echocardiograms within 6 months of the registry visit. All echocardiograms followed a standardized protocol, and were interpreted by the same cardiologist. PH was defined by a tricuspid regurgitant jet velocity >2.8 m/s, corresponding to a PASP >40 mmHg. Classification of grade 2 diastolic dysfunction (impaired left ventricular relaxation with elevated left atrial pressure) required a transmitral E/A ratio ≥ 0.8, and a transmitral to myocardial relaxation E/e’ ratio ≥ 15. Mitral annular calcification (MAC) was visually assessed, and considered evidence of extraosseous calcification. Associations between MAC and PH were analyzed with logistic regression, adjusted for age, sex, BMI, diastolic dysfunction, mitral regurgitation, left atrial dilation, and hematocrit.

Results:
From 2006-2013, 795 registry patients were screened preoperatively by echocardiography. Most were male (56%) and black (61%) with a mean age of 56 years. The majority (74%) received dialysis (13% peritoneal, 61% hemodialysis), for an average 2.8 years prior to the registry visit. PH, MAC, and AV shunts were present in 17%, 28%, and 62%; respectively. Relative to patients without MAC, those with MAC had higher odds of PH (OR
adj
=1.80; 95% CI: 1.17 – 2.78), which was not impacted by adjustment for AV shunts (OR
adj
= 1.78; 95% CI: 1.15 – 2.76). Further adjustment for years of dialysis modestly attenuated the association (OR
adj
= 1.55; 95% CI: 0.99 – 2.43).

Conclusion:
MAC is associated with higher odds of PH in severe CKD, irrespective of factors associated with PASP in the general population (age, sex, BMI), sources of pulmonary congestion (diastolic dysfunction, mitral regurgitation, and left atrial dilation), and causes of hyperdynamic circulation (hematocrit). The association is independent of hemodialysis shunts and dialysis vintage.