Vascular Calcification Slows But Does Not Regress After Kidney Transplantation.

INTRODUCTION: Medial arterial calcification is a common and progressive lesion in end-stage renal disease that is associated with poor cardiovascular outcomes. Whether this lesion can be arrested or reversed is unknown, and was examined retrospectively by measuring progression of breast arterial calcification before and after kidney transplantation. METHODS: Arterial calcification was measured on serial mammograms from patients with previous kidney transplantation and compared to measurements performed before transplantation or in patients on the active waitlist. Serum creatinine >2.0 mg/dl after transplantation or warfarin use were exclusions. RESULTS: Median (interquartile range) progression of arterial calcification was 12.9 mm/breast per year (5.9 to 32.6) in 34 patients before or awaiting transplantation compared to just 1.2 mm/breast per year (-0.54 to 5.1) in 34 patients after transplantation (P < 0.001). Slowing of progression was also seen in longitudinal analyses of patients with mammograms performed both before and after transplantation. Duration of end-stage renal disease before transplantation but not age, diabetes, baseline calcification, or serum chemistries correlated with progression after transplantation. Significant regression was not observed in any patient. CONCLUSION: In this first quantitative study of the effect of kidney transplantation, medial arterial calcification appeared to slow to rates seen in patients with normal renal function, indicating that the effect of renal failure may be completely abrogated. Overall, however, there was no significant regression, suggesting that calcification is irreversible and emphasizing the importance of prevention. Duration of pretransplant end-stage renal disease but not baseline calcification was a determinant of progression, consistent with cumulative, permanent changes to arteries that promote calcification.

Warfarin Accelerates Medial Arterial Calcification in Humans.

OBJECTIVE: Warfarin is associated with medial arterial calcification in humans, but the magnitude and specificity of this effect and the role of other risk factors are unknown. Using serial mammograms, progression of arterial calcification was compared in women receiving no anticoagulants, warfarin, or other anticoagulants, and before, during, and after warfarin use. Approach and Results: Warfarin users with mammograms were identified by computerized searches of medical records that included renal function and diabetes mellitus. Lengths of calcified arterial segments were measured, with progression expressed as millimeters per breast per year and presented as medians and interquartile range (IQR). In women with normal renal function (estimated glomerular filtration rate >60 mL/minute per 1.73 m2), progression was 3.9-fold greater in warfarin users: 9.9 (3.8-16) versus 2.5 (0.7-6.7) in controls, P=0.0003, but not increased in users of other anticoagulants. In longitudinal analyses, progression increased from 2.1 (IQR, 0.3-3.9) to 13.8 (IQR, 7.8-38.7; P=0.011) after starting warfarin (n=11) and decreased from 8.8 (IQR, 1.1-10) to 1.9 (IQR, -10 to 6.7; P=0.024) after discontinuation of warfarin (n=13). Progression of calcification was similar in warfarin users with chronic kidney disease (7.3 [IQR, 3.6-17], n=29) but markedly accelerated in warfarin users with end-stage renal disease (47 [IQR, 31-183], n=11; P=0.0002). Progression was similar in diabetic and nondiabetic warfarin users (10.1 [IQR, 3.8-24] versus 7.8 [IQR, 3.6-15]) and did not correlate with age (r=0.09) or duration of warfarin therapy (r=0.12). CONCLUSIONS: Warfarin significantly accelerates medial arterial calcification in humans. This effect is markedly augmented in end-stage renal disease.

Progression of Medial Arterial Calcification in CKD.

INTRODUCTION: Medial arterial calcification is common in chronic kidney disease (CKD) and portends poor clinical outcomes, but its progression relative to the severity of CKD and the role of other risk factors is unknown because of the lack of reliable quantification. METHODS: Calcification of breast arteries detected by mammography, which is exclusively medial and correlates with medial calcification in peripheral arteries and with cardiovascular outcomes, was used to measure the progression of medial arterial calcification in women with CKD and end-stage renal disease (ESRD). Measurements showed intra- and interobserver correlations of 0.98, an interstudy variability of 8% to 11%, and a correlation with computed tomographic measurements of 0.92. RESULTS: Progression of calcification was measured in 60 control subjects (estimated glomerular filtration rate (eGFR) ≥ 90 ml/min per 1.73 m2) and 137 subjects with CKD (eGFR < 90 ml/min per 1.73 m2). Progression in control subjects was linear over time and independent of age. The rate of progression was increased in CKD but only at eGFR < 40 ml/min per 1.73 m2 (median, 8.1 vs. 3.9 mm/breast/yr in controls; P = 0.006). Progression accelerated markedly in subjects with ESRD (median, 20 mm/breast/yr; n = 36), but did not differ from controls after kidney transplantation (n = 25). Diabetes significantly augmented progression in subjects with CKD and ESRD but not in controls. CONCLUSION: Mammography is a convenient and reliable method to measure the progression of medial arterial calcification. Progression does not increase until advanced stages of CKD, accelerates markedly in ESRD, and returns to control rates after kidney transplantation. Diabetes significantly increases progression in CKD and ESRD.