Serum calcification propensity is associated with renal tissue oxygenation and resistive index in patients with arterial hypertension or chronic kidney disease

Abstract

Background: 

Arterial calcifications increase arterial stiffness and are associated with a faster decline of kidney function in patients with arterial hypertension (AH) and/or chronic kidney disease (CKD). Yet the underlying mechanisms linking arterial calcifications, vascular stiffness and renal function decline are incompletely understood. A novel in-vitro blood test evaluates the propensity of patient's serum to prevent the formation of calcifications by measuring the maturation time of calciprotein particles (CPP) [transformation time of amorphous calcium phosphate-containing primary CPP to crystalline hydroxyapatite-containing secondary CPP (T₅₀)]. We hypothesized that a high arterial stiffness and a high propensity to calcify may be associated with high renal vascular resistance and low renal tissue oxygenation.

Methods: 

T₅₀ was measured in patients with AH and a preserved renal function, in CKD patients and in healthy controls, a lower T₅₀ indicating a higher risk of calcification. Pulse wave velocity (PWV) was assessed as a measure of arterial stiffness, and renal resistive index was measured by renal Doppler ultrasound. Renal tissue oxygenation was measured by blood oxygenation level-dependent MRI using the mean R2^* values of the cortex, the medulla and layers of renal parenchyma. A high R2^* value corresponds to a low tissue oxygenation.

Results: 

Mean T₅₀ was 246 ± 129 min in 58 CKD patients, 275 ± 111 min in 48 AH patients and 324 ± 96 min in 39 healthy controls (P_anova = 0.008). In multivariable adjusted linear regression analysis, serum T₅₀ correlated negatively with circulating calcium and phosphate levels, mean cortical and medullary R2^*, PWV, renal resistive index and being hypertensive. PWV was positively associated with R2^* levels of outer and inner layers of renal parenchyma.

Conclusion: 

The current study shows that hypertensive patients with preserved renal function as well as CKD patients have a higher risk of calcification than controls. High arterial stiffness and calcification propensity are linked to low renal tissue oxygenation and perfusion in hypertensive and CKD patients. These results provide new insights on the relationships among arterial stiffness, renal tissue oxygenation and the risk of developing CKD.