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Sivakumar Sridharan, MBBS, MRCP (UK), PhD, (@sayitmyway) is currently a nephrology fellow at Royal London Hospital, London as part of the North London Nephrology Training Program. Dr. Sridharan received his MBBS from Madras Medical College in Chennai, India and his PhD from the University of Herfordshire, UK. He is interested in understanding the relationship between physical activity and CKD. He is also interested in energy expenditure, dialysis dosing and physical activity in ESRD.
As we are entering the final week of NephMadness, the Hypertension Region has created a lot of discussion amongst the participants as much about the controversy of the region winner as the evidence behind the topic itself. #BlueRibbonFail generated so many responses on social media that the members of Blue Ribbon Panel felt compelled to provide an explanation. But, is choosing BP for kidney protection contrary to the practice of evidence-based medicine?
There was a time when high blood pressure (BP) with aging was considered essential for normal functioning of the heart (hence the term Essential Hypertension!). We have been disillusioned from this belief – thanks to the large body of evidence that have proved beyond doubt that hypertension is linked to cardiovascular disease (CVD). Over the last three decades, many studies have demonstrated various pathophysiological cardiovascular alterations due to hypertension – including, but not limited to, left ventricular hypertrophy, cardiovascular events (especially stroke), ventricular fibrosis, and endothelial dysfunction. Needless to say, treating hypertension prevents or, at the very least, reduces the risk of these ill effects. In fact, the volume of evidence for cardiovascular benefit is so large that a member of the Blue Ribbon Fail even commented that they find it boring! However, I see it as a tribute to the concept of hypertension and CVD due to the repeatability of the outcome effect time and time again.
The much talked about SPRINT study published last year showed reduction in all-cause mortality and cardiovascular events with intensive BP reduction. Though the ideal BP target is an area of ongoing debate, there is no denying the fact that optimal BP management is an important modifiable risk factor for CV benefit. But, how does this stack up against the evidence supporting hypertension treatment to reduce the risk of renal progression?
Sub-group and post-hoc analyses of some RCTs have suggested possible benefit of BP reduction in slowing the progression of renal disease. For example, the MDRD trial showed better outcomes with lower BP in patients with more than 1 g of proteinuria. However, the study data suggests that slowing down of GFR decline was related to proteinuria as depicted by better GFR in patients with similar mean arterial pressure and lower levels of proteinuria. Similarly, a post-hoc analysis of RENAAL study showed better renal outcomes in diabetic patients. Here again, the mean urine albumin-creatinine ratio of study participants was >1000 mg/g. Even a recently published systematic review and meta-analysis exploring renal outcomes with intensive BP control was left wanting for more evidence in CKD patients without proteinuria.
There are some points worth mentioning about the linkage between hypertension, CVD, and CKD progression. Firstly, the benefit of intensive BP control for kidney protection is not as universally applicable as it is for CVD prevention. There may be certain subgroups of patients who may benefit in terms of renal outcomes though we need more evidence adjusting for confounding factors in these subgroups. Secondly, the commonest cause of death in CKD patients is cardiovascular mortality (though not solely attributable to hypertension). They are more likely die with kidney disease than because of it. This highlights the vital role of BP control primarily for CVD protection than for renal outcomes.
The nephrologist in me would like to hold on to any sliver of hope that these studies provide in terms of renal protection. But, the simple clinician in me draws me back to the comprehensive (albeit boring!) demonstration of the benefit of BP control for cardiovascular benefit. The Cinderella of BP for kidney protection has had a really good run in the Big Dance of Nephrology until now but can it survive the challenge of stronger contenders for the title? Only time will tell.