Italian Audit on Therapy of Hypertension in Chronic Kidney Disease: The TABLE-CKD Study Luca De Nicola,* Roberto Minutolo,* Pasquale Zamboli,* Raffaele Cestaro,† Luigi Marzano,† Paolo Giannattasio,† Claudio Cristofano,‡ Stefano Chimienti,‡ Vincenzo Savica,§ Guido Bellinghieri,§ Francesco Rapisarda,¶ Pasquale Fatuzzo,¶ and Giuseppe Conte,* for the Investigators of TArget Blood Pressure LEvels in Chronic Kidney Disease (TABLE in CKD) Study Groupʈ A large body of evidence supports the validity of decreasing blood pressure to target levels in patients with essential hypertension to prevent cardiovascular disease. This issue becomes even more critical in chronic kidney disease because of the remarkably greater risk for cardiovascular fatal and nonfatal events. Indeed, renal patients should maintain blood pressure levels less than those suggested for the general population. Paradoxically, management of hypertension in this high-risk patient population is far from optimal and certainly worse with respect to essential hypertension. The Target Blood Pressure Levels in Chronic Kidney Disease (TABLE-CKD) study, performed in Italian patients with mild to advanced chronic kidney disease regularly followed-up by nephrologists, has shown that the prevalence of patients at target blood pressure is less than 20%. The assessment of antihypertensive strategy in these patients, however, suggests that there is room for improvement; in particular, a more aggressive treatment of volume expansion may amelio- rate hypertension control in this population characterized by a high salt sensitivity of blood pressure. Semin Nephrol 25:425-430 © 2005 Elsevier Inc. All rights reserved. KEYWORDS renal insufficiency, hypertension, cardiovascular disease, guidelines, low-salt diet, diuretic t is well established that the burden of cardiovascular (CV) Similarly, a recent large trial that evaluated the relationship Irisk is considerable across the entire spectrum of chronic between renal dysfunction and CV outcome after myocardial kidney disease (CKD) stages.1,2 A recent observational pro- infarction found that each reduction of estimated GFR by 10 spective study in a large community-based population has units below 81 mL/min/1.73 mo2 is coupled with a 10% shown that, at an estimated glomerular filtration rate (GFR) increment in the risk for death and nonfatal CV events.4 of less than 60 mL/min/1.73 mo2, a graded and strong asso- Finally, other recent studies in patients with CKD of various ciation between GFR decrease and risk for CV fatal and non- origin and degree have shown that over 5 to 6 years of fol- fatal events becomes evident, with the risk reaching a value low-up evaluation, the prevalence of CV events or death is 2 approximately 5 to 6 times greater in patients with predialytic to 20 times greater than that of renal events, such as doubling CKD as compared with patients with normal renal function.3 of serum creatinine level or initiation of a replacement ther- apy.4-7 Indeed, the high mortality of CKD patients provides a reasonable explanation to the “paradox of missing dialysis *Division of Nephrology, Second University of Naples, Naples, Italy. ¶Division of Nephrology, University of Catania, Catania, Italy. patients,” that is, the major disproportion between the size of †Division of Nephrology, Community Hospital in Sapri, Sapri, Italy. the nondialytic and dialytic CKD population, with a ratio of ‡Division of Nephrology, Community Hospital in Galatina, Galatina, Italy. about 50:1, currently observed in the United States.8 §Division of Nephrology, University of Messina, Messina, Italy. In this scenario, maintenance of low blood pressure (BP) ʈ See appendix for the complete list of authors. values likely becomes an essential intervention in CKD pa- Supported in part by a government grant from the Ministero della Istruzione, Università, e Ricerca, Rome, Italy (L.D.N.) in 2003. tients because they have more frequent, severe, and longer Address reprints requests to Professor Luca De Nicola, Via S.A. Capodi- exposure to hypertension than patients without renal dis- monte, 46, 80131 Napoli, Italy. E-mail: [email protected] ease.1,2 Moreover, in CKD the BP levels strictly correlate with 0270-9295/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. 425 doi:10.1016/j.semnephrol.2005.05.014 426 L. De Nicola et al. left ventricular growth,9 that is, a potent independent predic- tor of CV mortality/morbidity.10 On the other hand, a more intensive antihypertensive treatment in moderate CKD pre- vents the development of CV events during the predialytic phase,11,12 and, as suggested by a retrospective study,13 ame- liorates survival in the subsequent dialytic stage. Overall, these data indicate that hypertension plays a role in deter- mining the CV risk for CKD patients that certainly is not inferior, but probably is greater, as compared with the gen- eral population in whom it accounts for a population-attrib- utable risk for myocardial infarction of 18%.14 Figure 1 Percentage of patients with systolic and diastolic blood pressure values at goal. Values were considered at goal if less than 130/85 mm Hg in nonproteinuric patients and less than 125/75 mm BP Targets in CKD Hg in the presence of proteinuria greater than 1 g/d (s), or if less than 130/80 mm Hg, regardless of the degree of proteinuria (o). More than 6 years ago, the National Kidney Foundation (NKF) and the Joint National Committee (JNC VI) recom- mended maintenance of BP values at less than 130/85 mm Hg to proposed BP targets for CKD patients in the real world of in nonproteinuric CKD patients and less than 125/75 mm Hg clinical practice and to identify barriers to implementation of in the presence of proteinuria greater than 1 g/d.15,16 These guidelines on BP control. The survey has been performed in recommendations have been emphasized further in the sev- 19 Nephrology Units situated in Italian universities or com- enth report of JNC that identifies the value of less than munity hospitals. The sample of studied patients was derived 130/80 mm Hg as the BP target in patients with CKD, regard- from the population of nondialyzed and nontransplanted less of the degree of proteinuria.17 Similarly, the latest version CKD patients with a GFR estimated by the Cockcroft-Gault of the European guidelines for the management of hyperten- equation (eGFR) to be 70 mL/min/1.73 mo2 or less who sion have stated that in CKD patients it is advisable to reduce regularly received outpatient care in the involved nephrology BP intensively to the lowest tolerated level.18 clinics. To best analyze the management of hypertension by The necessity of low BP values in CKD is derived mainly nephrologists, we excluded patients with follow-up evalua- from the evidence of better CV protection by means of opti- tion in the nephrology clinic of less than 6 months. Patients mal BP control in the general population, and especially in with identified or suspected acute renal failure also were high-risk patients.17,19 Furthermore, interventional trials excluded. Therefore, we selected 713 patients for the study. aimed at the nephroprotective effects of tight BP control have Data were collected from September 2002 to March 2003. shown that intensive hypertension control is practicable in For a patient’s BP to be considered at goal, the BP had to be CKD patients.20-24 Nevertheless, prospective studies are re- less than the targets indicated by the NKF and JNC VI and quired to quantify the impact of entity of BP control on the published before the beginning of the study,15,16 that is, less degree of CV protection in the CKD population. than 130/85 mm Hg in nonproteinuric patients and less than Despite the critical role of antihypertensive treatment, 125/75 mm Hg in the presence of proteinuria greater than 1 management of hypertension persistently has been unsatis- g/d. Patients therefore were divided into 2 groups, reaching factory in CKD patients, with most of them showing BP levels the target (Target group, n ϭ 119) and not reaching the target higher than the proposed target values.2,23,25-27 In particular, (No Target group, n ϭ 594) on the basis of both the systolic in the 1988 to 1994 National Health and Nutrition Exami- BP (SBP) and diastolic BP (DBP) values at the study visit. nation Survey (which was the previous largest survey on this On average, BP was 116 Ϯ 9/71 Ϯ 7 mm Hg in the Target issue performed in almost 500 CKD patients from a total group and 143 Ϯ 15/83 Ϯ 9 mm Hg in the No Target group population of 17,000 patients), only 11% of CKD hyperten- (P Ͻ .0001). Most patients showed BP values above the levels sive patients had their BP levels reduced to less than 130/85 recommended by guidelines at the time of the study (Fig 1). mm Hg.28 In all these previous studies, however, information Specifically, only 17% of patients had both SBP and DBP at not only was outdated, but also generally was limited to the target, with the systolic goal being reached less frequently entity of BP control with no data provided on antihyperten- with respect to the diastolic target. Adequacy of antihyper- sive treatment. tensive intervention was even worse (13%) when considering the targets more recently proposed by JNC 7, that is, less than 130/80 mm Hg independently from the degree of proteinuria Target BP Levels in (Fig 1). Furthermore, only 40% of patients had their BP re- CKD (TABLE-CKD) Study duced to less than 140/90 mm Hg, that is, the treatment goal for individuals with hypertension and no compelling indica- We performed a comprehensive audit, the TABLE-CKD tions. study, on hypertension management in a large sample of The main clinical and laboratory differences between the Italian patients regularly followed-up by outpatient nephrol- Target and No Target patients are shown in Table 1.