Association between Aortic Calcification, Cardiovascular Events, and Mortality in Kidney and Pancreas-Kidney Transplant Recipients

Abstract

word count: 246 16 Word count: 3110 Abstract 34 Background: Cardiovascular (CV) disease is the leading cause of death in kidney and 35 simultaneous pancreas-kidney (SPK) transplant recipients. Assessing abdominal aortic 36 calcification (AAC), using lateral spine x-rays and the Kaupilla 24-point AAC (0-24) score, 37 may identify transplant recipients at higher CV risk. 38 Methods: Between the years 2000-2015, 413 kidney and 213 SPK first transplant recipients 39 were scored for AAC at time of transplant and then followed for CV events (coronary heart, 40 cerebrovascular or peripheral vascular disease), graft-loss and all-cause mortality. 41 Results: The mean age was 44 ± 12 years (SD) with 275 (44%) having AAC (26% moderate: 42 1-7 and 18% high: ≥8). After a median of 65 months (IQR 29-107 months), 46 recipient's 43 experienced CV events, 59 died and 80 suffered graft loss. For each point increase in AAC, 44the unadjusted hazard ratios (HR) for CV events and mortality were 1.11 (95% CI 1.07-1.15) 45 and 1.11 (1.08-1.15). These were similar after adjusting for age, gender, smoking, transplant 46 type, dialysis vintage and diabetes: aHR 1.07 (95% CI 1.02-1.12) and 1.09 (1.04-1.13). For 47 recipients with high versus no AAC, the unadjusted and fully-adjusted HR for CV events 48 were 5.90 (2.90-12.02) and 3.51 (1.54-8.00), for deaths 5.39 (3.00-9.68) and 3.38 (1.71-6.70), 49 and for graft loss 1.30 (0.75-2.28) and 1.94 (1.04-3.27) in age and smoking history-adjusted 50 analyses. 51 Conclusion: Kidney and SPK transplant recipients with high AAC have 3-fold higher CV 52 and mortality risk and poorer graft outcomes than recipients without AAC. AAC scoring may 53 be useful in assessing and targeted risk-lowering strategies. 54 55 56 KEY WORDS; vascular calcification, cardiovascular disease, kidney transplant, 57 simultaneous pancreas-kidney transplant, mortality.

Aorto-Iliac Artery Calcification Prior to Kidney Transplantation

“…The literature on abdominal aorta calcification (AAC) assessment by plain pelvic X-ray or dual X-ray absorptiometry, using visual grading scales, is more extensive [13]. Studies evaluating this method showed results similar to our findings, with significant associations of a high-AAC with all-cause mortality and cardiovascular events in multivariable Cox regression analyses [12,20,21]. Timing of the imaging procedure in previous studies is an important difference compared with the current study, as imaging procedures were performed after transplantation and at the physician's discretion, instead of CT procedures during the screening prior to transplantation.…”

“…CAC, expressed as Agatston score by non-contrast enhanced cardiac computed tomography (CT), demonstrated progression within four years in prevalent kidney transplant recipients and is associated with myocardial infarction and mortality [14][15][16][17][18]. Aorto-iliac calcification, by plain pelvic X-ray, dual X-ray absorptiometry, or semi-quantitative CT assessment, was associated with inferior overall patient survival [12,[19][20][21][22][23][24].…”

Myocardial perfusion reserve of kidney transplant patients is well preserved

“…Increasing AAC score, especially score values greater than 8-15, has been associated with severely increased risk for CV events in dialysis patients [29][30][31]. AAC score 8 has been used as a cut-off value for high calcification in transplant patients [32,33]. Lewis et al showed, that there is a continuous 7-8% increase in risk of CV events for each 1 point increase in AAC score without an exact cut-off point [33].…”

“…AAC score 8 has been used as a cut-off value for high calcification in transplant patients [32,33]. Lewis et al showed, that there is a continuous 7-8% increase in risk of CV events for each 1 point increase in AAC score without an exact cut-off point [33]. Based on these previous studies, AAC-score 0 in 13/17 patients and the highest AAC score 8/24 in our study should indicate mild to moderate CV risk.…”

Loss of PKCα increases arterial medial calcification in a uremic mouse model of chronic kidney disease

“…These cardiovascular complications are the main causes of mortality in patients with CKD. Vascular calcification is also associated with a higher mortality risk in CKD patients following kidney transplantation, and may be a predictor of poor graft outcomes 7 . As existing treatments for vascular calcification in CKD patients are limited, there is an urgent need to identify new therapeutic targets for this disease.…”