Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease.

BACKGROUND: The role of antioxidant status on microvascular blood flow and glomerular filtration (eGFR) in patients with type 2 diabetes and hypertension whose risk of progressive renal disease varies by ethnicity is unknown. METHODS: Adult, non-Caucasian (n = 101) and Caucasian (n = 69) patients with type 2 diabetes, hypertension and/or microalbuminuria and an eGFR > 45 mL/min/1.73 m2 were randomised to receive 400 IU vitamin E and/or 20 µg selenium daily or matching placebo. eGFR (CKD-EPI) was measured at baseline, 3,6 and 12 months and renal blood flow by contrast-enhanced ultrasonography in a sub-group (n = 9) at baseline and 3 months by assessing the area under the time intensity curve (TIC). Circulating glutathione peroxidase 3 (GPx-3) activity was measured as a biomarker of oxidative defence status. RESULTS: The time to change in eGFR was shortest with combined vitamin E and selenium than usual care (5.6 [4.0-7.0] vs 8.9 [6.8-10.9 months]; p = 0.006). Area under the TIC was reduced compared to baseline (38.52 [22.41-90.49] vs 123 [86.98-367.03]dB.s; P ≤ 0.05 and 347 [175.88-654.92] vs 928.03 [448.45-1683]dB.s; P ≤ 0.05, respectively] at 3 months suggesting an increase in rate of perfusion. The proportional change in eGFR at 12 months was greater in the group whose GPx-3 activity was above, compared with those below the cohort median (360 U/L) in the non-Caucasian and the Caucasian groups (19.1(12.5-25.7] % vs 6.5[-3.5 to 16.5] % and 12.8 [0.7 to 24] % vs 0.2 [-6.1 to 6.5] %). CONCLUSION: In these patients with type 2 diabetes and early CKD, antioxidant treatment derepresses renal blood flow and a rise in eGFR correlated directly with GPx-3 activity. SIGNIFICANCE: Diabetes mellitus is the world's leading cause of end-stage renal disease which has a predilection for black and minor ethnic groups compared with Caucasians. The differences in risk despite the benefits of conventional care may be related to oxidative stress. We found that glomerular filtration and renal blood flow is suppressed when renal function is preserved in high-risk patients with type 2 diabetes. Conventional care supplemented with selenium - the co-factor for glutathione peroxidase-3 (GPx-3) - improves renal perfusion and increase glomerular filtration according to host antioxidant defence determined by GPx-3 activity. Circulating GPx-3 activity warrants further investigation as a novel biomarker of reversible haemodynamic changes in early diabetic kidney disease to better enable targeting of renoprotective strategies.

Telemonitoring: use in the management of hypertension.

Hypertension is a major modifiable risk factor for cardiovascular, retinal, and kidney disease. In the past decade, attainment rates of treatment targets for blood pressure control in the UK and US have increased; however, <11% of adult men and women have achieved adequate blood pressure control. Technological advances in blood pressure measurement and data transmission may improve the capture of information but also alter the relationship between the patient and the provider of care. Telemonitoring systems can be used to manage patients with hypertension, and have the ability to enable best-practice decisions more consistently. The improvement in choice for patients as to where and who manages their hypertension, as well as better adherence to treatment, are potential benefits. An evidence base is growing that shows that telemonitoring can be more effective than usual care in improving attainment rates of goal blood pressure in the short-to-medium term. In addition, studies are in progress to assess whether this technology could be a part of the solution to address the health care needs of an aging population and improve access for those suffering health inequalities. The variation in methods and systems used in these studies make generalizability to the general hypertension population difficult. Concerns over the reliability of technology, impact on patient quality of life, longer-term utility and cost-benefit analyses all need to be investigated further if wider adoption is to occur.