Blog entry by Meguid El Nahas
In this month KI, Eriksen and colleagues reports on a Norwegian longitudinal study of the general population examining the links between age related decline in GFR and Blood Pressure (at baseline) (BP).
The study did NOT show any association between baseline BP parameters and the rate of decline of measured GFR (mGFR) in an older general population with exclusion of those known to have cardiovascular disease or DM.
The study has a number of advantages and strengths:
1. It is a general population cohort study where over a period of 5.6 years of follow up the GFR was measured by iohexol clearance.
2. Measured GFR (mGFR) showed a decline of aroun 098-0.9ml/min/year consistent with previous observations that GFR is lost at a rate ~1ml/min/year after the age of 50.
3. The study Renal Iohexol Clearance Survey in Tromso 6 (RENIS-T6) also compared mGFR with eGFRCr and eGFRCys and find thme wanting as their values, compared to mGFR, in the general population with near normal renal function were confounded by non-renal variables such as inflammation:
4. mGFR was repeated over the 5.6 years observation period.
5. BP was measured in day and night time as well as ambulatory (ABPM) in this study: http://www.ncbi.nlm.nih.gov/pubmed/22278141
The study failed to show an association between baseline BP values and the subsequent rate of mGFR decline with time.
This observation agrees with older ones showing the impact of BP on the decline in GFR was primarily linked to bouts of accelerated hypertension jeopardising GFR in a stepwise fashion, whilst a steadily elevated BP was not associated with a faster rate of GFR decline. In fact, a meta-analysis of 10 RCTs back in 2002 failed to show a strong association between BP and incident CKD: http://www.ncbi.nlm.nih.gov/pubmed/11981255
This was supported by observations that non-accelerated, mild to moderate, hypertension was not associated with nephrosclerosis in the general population: http://www.ncbi.nlm.nih.gov/pubmed/?term=freedman+appel%2C+1995
A limitation of the current study is the emphasis on Baseline BP and subsequent mGFR decline.
More emphasis on changes in BP control with time would have been more informative; in fact, their unadjusted data suggest that those whose BP (MAP) increased with time had slower mGFR decline...
whilst those treated for hypertension had faster rate of decline (raising the possibility that antihyeprtensive agents, including RAAS inhibitors may have detrimental effects on GFR decline with time)...
In spite of its limitations this observation, with accurate GFR measurements and thorough BP recordings, draw attention to the fact that the links between mild to moderate BP elevation and age-related decline in GFR do not show a linear association.
Confounders, may impact on that association including genetic factors (APOL1 genotype), obesity and environmental factors such as smoking as well as susceptibility to hypertension induced atherosclerosis and its impact on renal perfusion and function.
The conclusion of this observation has to be:
There is more to the link between hypertension and CKD decline than elevated Blood Pressure; other confounders and comorbid factors have to be taken into consideration. This notion may lead to a more targeted and individualised approach to the management of hypertension in older people based on the presence or absence of other comorbid confounders. This has been emphasised by the JNC8 recommendations: