Blood pressure is very important for the large numbers of people who are now thought to have CKD—around 13% of the US population from the latest National Health and Nutrition Examination Survey report,1 with attendant cardiovascular risk becoming observable after quite small reductions in GFR.2 In nephrology, we do therefore appreciate that renal and cardiovascular risk are heavily intertwined and share several copromoting mechanisms (eg, elevated BP, proteinuria, and dyslipidemia); discovering and properly addressing these matters is a health care priority. Patients with CKD die of cardiovascular disease as much as, or more often than, their disease progresses to requiring dialysis; the “survivors” then reach dialysis, where again it is cardiovascular disease that primarily causes their demise.3 The evidence that treating BP helps to reduce renal progression and attendant cardiovascular disease is strong, although far too much uncertainty remains about what target BP value to aim for, what interventions work best, and whether the known abnormalities in diurnal BP rhythm in CKD are of any prognostic importance.4 This uncertainty has been partially obscured by surprisingly robust guideline recommendations. Given the importance of detecting BP elevation and of dealing with it efficiently and promptly, it is both exciting and challenging to see a report like the one by Minutolo and colleagues5 from Naples in which a large cohort of 436 hypertensive patients with CKD, who were studied between 2003 and 2006 in 4 Italian renal units, had ABPM with follow-up until they reached a prespecified renal or cardiovascular end point or until September 30, 2010. Importantly, patients were seen by the same nephrologists, who adhered to the therapeutic goals recommended by the Kidney Disease Outcomes Quality Initiative (BP <130/80 mm Hg). All patients were instructed to restrict dietary salt (<6 g/d of sodium chloride) and protein (≤0.8 g/kg of body weight per day). All prescribed antihypertensive medications were commercially available and totally reimbursed.5 These conditions are tough to emulate in many clinical settings, and yet aspiration to achieve such clinical excellence is fundamental to overall success. The important findings from this prospective cohort study include the demonstration that ABPM facilitates better risk profiling of an unselected CKD population typically seen in a nephrology clinic. In other words, the authors demonstrate that ABPM predicts renal and cardiovascular risk better than office BP values do. In fact, office BP values were not helpful except for substantially elevated systolic BP. Most patients with CKD in a clinic would not demonstrate such high BP values. Only 2 studies6,7 have previously compared the prognostic role of ABPM and office BP measurement in patients with CKD; this third study—with a much larger, more heterogeneous population—is important as proof of concept. In addition, and in contrast to those previous investigations, this new study clearly shows that the predictive value of ABPM was independent of other risk factors, such as diabetes mellitus, history of cardiovascular disease, proteinuria, anemia, and GFR.5 So, which of the many ambulatory BP averages and data proved the most rewarding to measure or derive? Nighttime SBP was a stronger predictor than daytime SBP for both adverse renal and cardiovascular end points, with an increased risk occurring for daytime SBP higher than 135 mm Hg and nighttime SBP higher than 124 mm Hg, respectively. In contrast, DBP had a different association with renal and cardiovascular end points; whereas daytime values allowed a better definition of renal prognosis, nocturnal DBP better predicted the risk of fatal/nonfatal cardiovascular events. Two hundred thirty-nine patients (54.8%) achieved only the daytime BP target (<135/85 mm Hg) and 189 patients (43.3%) only the nighttime target (<120/70 mm Hg), while 166 patients (38.1%) achieved both targets and 174 patients (39.9%) achieved neither target. Patients who did not achieve either target had the greatest risk of cardiovascular (HR, 1.99) and renal (HR, 2.65) end points. Another interesting study outcome was the demonstration that white coat hypertension was common (43.3%) in patients with CKD. This means that about half the patients had misrepresented daytime BP values. At the same time, about half the patients had unmeasured BP-related risk by being nondippers or nighttime BP risers. Reproducibility of these classifications has been assessed in other renal populations.8,9 A missed opportunity in this study would have been to examine all patients—including the “normotensive” ones—to determine whether there is any evidence of a J-shaped relationship between low BP and adverse cardiovascular outcomes (the so-called “reverse epidemiology” reported so frequently in nephrology10). Overtreatment of hypertension, especially in older patients with CKD (in whom organ [renal, cerebral, etc] perfusion is more likely to be adversely affected), has been disclosed by the use of ABPM and may be another important reason to use ABPM more precisely to characterize BP profiles.11 Of course, there will be those who will question the time, effort, and expense of running an ambulatory BP service. Naturally, it is all of those things, just as providing echocardiography is more demanding of time, effort, and money than is reliance on simple 12-lead electrocardiography for patients with congestive heart failure. Therefore, we still need a prospective study in which patients with CKD are randomized to BP therapy and BP levels derived from daytime home BP measurement or full ABPM. A specific aim could be to investigate the prospective impact of restoring a more physiological diurnal BP profile. Ambulatory BP monitoring is currently recommended by most authorities and guideline groups only for patients with symptomatic or unpredictable BP, and home BP measurement is acknowledged as another valid approach.12 We believe that there are selected cohorts of patients in whom the additional time, effort, and expense of doing ABPM is justified, and this new study by Minutolo and colleagues5 makes that case stronger for our patients with CKD. It is now harder to defend reliance on clinic BP measurement alone if we nephrologists are serious about targeted BP intervention. Correspondence: Dr Covic, Clinic of Nephrology, C. I. Parhon University Hospital, Gr T Blvd, Carol First No. 50, Iasi, 6600 Romania (email@example.com). Financial Disclosure: None reported. References 1. Foley RN Temporal trends in the burden of chronic kidney disease in the United States. Curr Opin Nephrol Hypertens 2010;19 (3) 273- 277PubMedGoogle Scholar 2. Matsushita Kvan der Velde MAstor BC et al. Chronic Kidney Disease Prognosis Consortium, Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375 (9731) 2073- 2081PubMedGoogle Scholar 3. Chertow GMLevin NWBeck GJ et al. FHN Trial Group, In-center hemodialysis six times per week versus three times per week [published correction appears in N Engl J Med. 2011;364(1):93]. N Engl J Med 2010;363 (24) 2287- 2300PubMedGoogle Scholar 4. Agarwal R Blood pressure goal in chronic kidney disease: what is the evidence [published online February 23, 2011]? Curr Opin Nephrol Hypertens PubMed10.1097/MNH.0b013e3283454332Google Scholar 5. Minutolo RAgarwal RBorrelli S et al. Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease. Arch Intern Med 2011;171 (12) 1090- 1098Google Scholar 6. Tripepi GFagugli RMDattolo P et al. Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular events-free hemodialysis patients. Kidney Int 2005;68 (3) 1294- 1302PubMedGoogle Scholar 7. Agarwal RAndersen MJ Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease. Kidney Int 2006;69 (7) 1175- 1180PubMedGoogle Scholar 8. Covic AMititiuc IGusbeth-Tatomir PGoldsmith DJ The reproducibility of the circadian BP rhythm in treated hypertensive patients with polycystic kidney disease and mild chronic renal impairment—a prospective ABPM study. J Nephrol 2002;15 (5) 497- 506PubMedGoogle Scholar 9. Haydar AACovic AAgharazii MJayawardene STaylor JGoldsmith DJ Systolic blood pressure diurnal variation is not a predictor of renal target organ damage in kidney transplant recipients. Am J Transplant 2004;4 (2) 244- 247PubMedGoogle Scholar 10. Covic AGusbeth-Tatomir PGoldsmith D Negative outcome studies in end-stage renal disease: how dark are the storm clouds? Nephrol Dial Transplant 2008;23 (1) 56- 61PubMedGoogle Scholar 11. Tomlinson LAHolt SGLeslie ARRajkumar C Prevalence of ambulatory hypotension in elderly patients with CKD stages 3 and 4. Nephrol Dial Transplant 2009;24 (12) 3751- 3755PubMedGoogle Scholar 12. Pickering TGWhite WBGiles TD et al. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens 2010;4 (2) 56- 61PubMedGoogle Scholar
Archives of Internal Medicine – American Medical Association
Published: Jun 27, 2011
Keywords: kidney failure, chronic,blood pressure,blood pressure determination
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