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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 (Panova = 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.

Background/aims: The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients., Methods: 24 patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150-300 mg/d or HCTZ 12.5 - 25 mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8. BOLD-MRI was also performed before and after an i.v. injection of 20 mg furosemide at week 0 and at week 8. BOLD-MRI data were analyzed by measuring the oxygenation in 12 computed layers of the kidney enabling to asses renal oxygenation according to the depth within the kidney and by the classical method of regions of interest (ROI)., Results: The classical ROI analysis of the data showed no difference between the groups at week 8. The analysis of renal oxygenation according to the 12 layers method shows no significant difference between aliskiren and HCTZ at week 8 before administration of furosemide. However, within group analyses show that aliskiren slightly but not significantly increased oxygenation in the cortex and decreased medullary oxygenation whereas HCTZ induced a significant overall decrease in renal tissue oxygenation. With the same method of analysis we observed that the response to furosemide was unchanged in the HCTZ group at week 8 but was characterized by an increase in both cortical and medullary oxygenation in aliskiren-treated patients. Patients responding to aliskiren and HCTZ by a fall in systolic blood pressure of >10 mmHg improved their renal tissue oxygenation when compared to non-responders., Conclusion: With the classical method of evaluation using regions no difference were found between aliskiren and HCTZ on renal tissue oxygenation after 8 weeks. In contrast, with our new method that takes into account the entire kidney, within group analyses show that aliskiren slightly increases cortical and medullary renal tissue oxygenation in hypertensive patients whereas HCTZ decreases significantly renal oxygenation at trough., (© 2015 S. Karger AG, Basel.)

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the reninangiotensin system) or alterations in sodiumintake in these patient groups, underlining the important role of renal sodiumhandling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans. [ABSTRACT FROM AUTHOR]