Renal Hypoxia: An Important Prognostic Marker in Patients with Chronic Kidney Disease

Abstract

Background: Blood oxygen level-dependent (BOLD)-MRI is a novel and noninvasive tool that can assess renal oxygenation. The R2* value is a parameter of tissue deoxyhemoglobin concentration detected by BOLD-MRI. The purpose of the current study was to determine the relationships between renal R2* values and clinical parameters and to determine whether renal R2* values were associated with the risk for progression of chronic kidney disease (CKD). Methods: Sixty patients with CKD were enrolled in this prospective observational study in China from March 2013 to August 2014. A region of interest-based BOLD-MRI was performed to obtain cortical and medullary R2* (CR2* and MR2*) values. Data on demographics and clinical characteristics were collected. The primary end point (CKD progression) was defined as an absolute 30% decline in the estimated glomerular filtration rates (eGFR; CKD-Epidemiology Collaboration equations) or initiation of dialysis during follow-up. Results: The CR2* and MR2* values in patients with CKD were significantly higher compared with those of healthy controls. The CR2* levels were positively associated with 24-h urinary protein excretion, blood urea nitrogen, creatinine, and uric acid but negatively associated with baseline eGFR, 24-h creatinine clearance, eGFR slope, serum albumin, and the use of angiotensin II type 1 receptor blockade. The CR2* levels had the highest areas under the curve during follow-up compared with the MR2* levels and medullary cortical ratios. The Kaplan-Meier survival analysis showed that patients with CKD in the lowest tertile of the CR2* levels had the best prognosis compared with the other 2 tertiles. Moreover, baseline eGFR and CR2* tertiles were associated with the progression of CKD in Cox proportional hazard regression models. Only CR2* tertiles correlated negatively with the eGFR slope. Conclusion: We have demonstrated that the clinical feasibility of BOLD-MRI to evaluate renal oxygenation and cortex hypoxia aggravates with the decline of renal function, and cortex hypoxia was a prognostic marker in the progression of CKD.

Cortical Perfusion and Tubular Function as Evaluated by Magnetic Resonance Imaging Correlates with Annual Loss in Renal Function in Moderate Chronic Kidney Disease

“…It is not yet clear if such modest change is due to the inherently lower sensitivity of BOLD MRI in evaluating cortical oxygenation [31] or whether the kidney compensates for the lower perfusion and maintains the oxygenation status. Unlike previous studies [26,27] reporting a significant association of cortical R2* with eGFR and eGFR_slope, we did not observe similar associations. We suspect this may be partly related to the moderate CKD in our study, limited range of eGFR values and the smaller number of subjects.…”

“…Only R2*_MC ratio showed significant differences between the CKD and control groups. The modest increase in cortical R2* is consistent with prior studies [26,27]. It is not yet clear if such modest change is due to the inherently lower sensitivity of BOLD MRI in evaluating cortical oxygenation [31] or whether the kidney compensates for the lower perfusion and maintains the oxygenation status.…”

“…Recent studies have reported that the cortical oxygenation as evaluated by BOLD MRI can predict future loss of renal function [26,27]. Another recent study evaluated BOLD and diffusion MRI in a large multicenter study in subjects with advanced CKD (mean eGFR 33.4 ± 7.2 mL/min/1.73 m 2 ) and demonstrated reduced renal cortical oxygenation and presence of renal fibrosis consistent with the chronic hypoxia hypothesis [28].…”

Impacts of Diabetes and an SGLT2 Inhibitor on the Glomerular Number and Volume in db/db Mice, as Estimated by Synchrotron Radiation Micro-CT at SPring-8

“…Chronic hypoxia induces tubulotinterstitial fibrosis, which in turn could decrease the GFR [ 54 ]. In this regard, cortical hypoxia predicts a progressive decrease in renal function in patients with chronic kidney disease [ 55 , 56 ]. In contrast, SGLT2 inhibitors induced hypoxia in the outer stripe of the outer medulla (OSOM), but not in the cortex.…”

The role of renal hypoxia in the pathogenesis of diabetic kidney disease: a promising target for newer renoprotective agents including SGLT2 inhibitors?

“…76 Moreover, various studies showed that cortical oxygenation independently predicts the progression of CKD by annual estimated glomerular filtration rate (eGFR) loss. [76][77][78] In addition, BOLD-MRI measurement has been combined with arterial spin labeling to quantify renal perfusion in patients with diabetes and stage 3 CKD. 79 The results indicated that cortical oxygenation in patients with mild to moderate CKD was reduced, although the measurement did not reach statistical significance.…”