suggest that cardiovascular and survival benefits are provided by an SBP target of 130 mm Hg or a DBP consistently >80 mm Hg be treated to maintain SBP 130/80 mm Hg for children ages 13 years and above.103 However, the cutoff age of 13 years in CKD patients was considered potentially problematic by conference participants because many pediatric patients with CKD have small stature and may have a lower BP than is typical for their age. The 2012 KDIGO BP guideline for pediatric CKD patients should be reconsidered in light of these new AAP normative data and other guidelines. Treatment targets Recommendation 6.2 in the 2012 KDIGO BP guideline suggests that SBP and DBP be lowered to values #50th percentile in children with CKD, particularly in those with proteinuria.1 This recommendation was based primarily on the Effect of Strict Blood Pressure Control and ACE-Inhibition on Progression of Chronic Renal Failure in Pediatric Patients (ESCAPE) trial, in which hypertensive pediatric CKD patients randomized to a mean arterial BP target of Hypertension in end-stage renal disease MANUEL MART´INEZ-MALDONADO Department of Medicine, Atlanta Veterans Administration Medical Center and Emory University School of Medicine, Atlanta, Georgia, USA Hypertension in end-stage renal disease. Patients with moderate to severe renal disease have a very high incidence of hypertension. In end-stage renal disease (ESRD) this is true regardless of the nature of the underlying renal disease. Nevertheless, patients with glomerular diseases and autosomal dominant polycyctic kidney disease are particularly vulnerable. Evidence is presented that ESRD hypertension is the result of extracellular volume expansion, increased or inappropriate response of the renin-angiotensin system and overactivity of the sympathetic system. In addition, the role of endothelin-1, nitiric oxide and other vasodilators, and abnormal ion channels in generating high blood pressure, is considered. Hypertension is a frequent complication of chronic renal failure (ESRD). Numerous studies have established that chronic parenchymal renal disease is the most common cause of secondary hypertension, accounting for approximately 5% of all patients with hypertension [1]. Hypertension is an independent risk factor for ESRD, particularly in African-Americans [2], but in many ESRD patients hypertension develops as a result of the intrinsic renal malady. For example, in chronic glomerular disease between 15% and 80% of patients have hypertension; the range is dependent on the underlying diagnosis, with the more severe glomerular diseases having higher incidence of hypertension [3, 4]. Virtually all patients with polycystic kidneys (ADPKD) develop hypertension by the time ESRD is present [5]. Tubulointerstitial disease is also associated with a high incidence of hypertension once ESRD is present [6]. PATHOPHYSIOLOGY The model of uninephrectomy and salt-loading hypertension in rats or other animals has been frequently used to study the hypertension of chronic renal disease [7]. Although this may be a valid paradigm of how expansion of extracellular volume can cause hypertension, the pathogenesis of elevated blood pressure in ESRD is more complex. Figure 1 shows factors that may influence blood pressure regulation at any given time, and that in the case of ESRD hypertension may be the result of multiple factors acting simultaneously or individually. Ultimately, changes in cardiac output or total peripheral resistance will determine blood pressure levels. I will discuss some of the evidence advanced to support a role of these factors in effecting changes in blood pressure regulation. SODIUM BALANCE The overwhelming evidence obtained so far favors an important role for extracellular volume and sodium balance in the hypertension of ESRD. Early in the course of ESRD plasma and extracellular fluid volumes are usually normal [8, 9]. Moreover, in 50% or more of ADPKD patients, hypertension is found at a time when changes in renal function cannot be detected [10]. Nevertheless, with few exceptions [11], most investigators [12, 13] have found expanded blood or extracellular fluid volumes in ESRD patients. Infusion of saline aggravates the hypertension of ESRD patients by preferentially distributing to the intravascular space, suggesting a similar fate for ingested salt [14]. Moreover, various studies have shown a correlation between exchangeable sodium and plasma volume, or between the former and extracellular fluid volume in mild to moderate renal insufficiency [9, 15] or in ESRD [12, 16, 17]. The precise mechanism by which volume expansion increases blood pressure is unknown, but the autoregulation theory of the pathogenesis of hypertension has been advanced as an explanation (Fig. 2). Some evidence for this sequence was initially obtained by Coleman, Granger and Guyton [18]; however, experiments by others revealed a more complex sequence of events in response to extracellular volume expansion in anephric subjects as well as in ESRD patients [19]. Kim and coworkers studied four anephric and six ESRD patients on maintenance hemodialysis [19]. The sequential study was carried out in the following five phases: (1) stable, dry control weight; (2) progressive volume expansion; (3) sustained volume expansion; (4) during volume depletion; and (5) again at dry control weight.