Sergio F. F. Santos

Pre- and Postdialysis Blood Pressures Are Imprecise Estimates of Interdialytic Ambulatory Blood Pressure

BP readings that are obtained in the dialysis unit are commonly used to make therapeutic decisions by clinicians and to predict morbidity and mortality by epidemiologists. Dialysis unit BP are also incorporated in the recent guidelines to target BP control. The magnitude of the difference, overestimation or underestimation, and agreement between dialysis unit BP and ambulatory BP (ABP) are unknown. Articles were selected from Medline to identify those that reported both ABP and dialysis unit BP in hemodialysis patients. Bias was calculated as the difference between dialysis unit and the corresponding ABP. Agreement limits between the BP measurement techniques were assessed by pooled SD of the difference using Bland-Altman methods. Predialysis systolic BP generally overestimated ABP by a variable amount. The heterogeneity between BP measurements did not allow for pooling of the estimates. The agreement limits between the two BP was 41.7 to -25.2 mmHg. Predialysis diastolic BP also generally overestimated the ABP with wide agreement limits (23.7 to -18.9 mmHg). In contrast, postdialysis BP underestimated average ABP with wide agreement limits for both postdialysis systolic BP (33.1 to -36.3 mmHg) and diastolic BP (19.3 to -23.9 mmHg). Dialysis unit BP measurements are imprecise estimates of ABP. Better methods are needed for the assessment of BP in hemodialysis patients for clinical decision making.

Out-of-office blood pressure monitoring in chronic kidney disease.

Blood pressure (BP) control is vital to the management of patients with chronic kidney disease (CKD) yet most treatment decisions use BPs obtained in the clinic. The purpose of this report is to review the importance of self-measured and automatic ambulatory BPs in the management of patients with CKD. Compared with clinic-obtained BPs, self-measured BP more accurately defines hypertension in CKD. Masked hypertension seems to be associated with higher risk of end-stage renal disease in CKD patients. Conversely, white-coat hypertension seems to be associated with better renal outcomes than those who have persistent hypertension. Ambulatory BP monitoring is the only tool to monitor BP during sleep, diagnose nondipping, and, as self-measured BPs, have greater prognostic power in CKD compared with clinic BP. In hemodialysis patients, self-measured BP, but not pre/post-dialysis BP, shares the combination of high sensitivity and high specificity of greater than 80% to make a diagnosis of hypertension with the reference standard of ambulatory BP monitoring. In addition, self-measured and ambulatory BPs seem to be better correlates of left-ventricular hypertrophy and mortality in hemodialysis patients compared with pre/post-dialysis BP. Emerging data suggest that out-of-office BP monitoring is superior to BP obtained in the clinic when predicting target-organ damage and prognosis. Out-of-office BP monitoring is recommended for the management of hypertension in all stages of CKD.

Long-term stability of serum sodium in hemodialysis patients.

Background: A direct relationship between dialysate-to-plasma sodium gradient, blood pressure and interdialytic weight gain exists in hemodialysis (HD) patients. The aim of this study was to delineate the long-term variability of serum sodium in HD patients. Methods: We performed a retrospective cohort analysis of serum sodium and other analytes routinely evaluated in 100 stable chronic HD patients observed for 12 months. Results: Individual levels across the cohort varied from 122 to 145 mM, but 12-month intraindividual coefficients of variation for sodium were low (pre-HD = 1.6%; post-HD = 1.8%) with overall variability similar to that related to laboratory assay variability especially when compared with other analytes (3.1–30.8%). Pre-HD serum sodium had a trend toward hyponatremia (mean 136 ± 0.8 mM). Conclusion: Serum sodium is stable over time in HD patients. Pre-HD serum sodium may be used as a parameter for individualizing dialysate sodium prescription.

Profile of interdialytic blood pressure in hemodialysis patients.

Background and Methods: Hypertension is a common problem in hemodialysis (HD). However, its behavior during the interdialytic period is not completely known and is infrequently monitored in clinical practice. Thus, for better understanding of interdialytic blood pressure (BP), we analyzed the interdialytic blood pressure profile using 44-hour ambulatory blood pressure monitoring (ABPM) data in 71 unselected, stable HD patients. Results: There was an increase in BP during the interdialytic period (awake day 1: 135/84 ± 23/14 mm Hg; awake day 2: 140/86 ± 22/15 mm Hg, p < 0.05; sleep day 1: 130/77 ± 24/15 mm Hg; sleep day 2: 136/80 ± 24/15 mm Hg, p < 0.05). The correlation between the average 44-hour BP and interdialytic weight gain (IDWG) was not significant (r = –0.07 for systolic BP and r = –0.09 for diastolic BP). The number of non-dipper patients was high, 77% on interdialytic day 1 and 83% on interdialytic day 2 for systolic BP. Uncontrolled hypertension (average 44 h BP ≧135/85 mm Hg) was diagnosed in 58 (55%) patients. Patients with uncontrolled hypertension had higher pre- and posthemodialysis BP, higher BP on each interdialytic day and night, and higher night/day diastolic BP ratio on the second interdialytic day. These patients were also taking a greater number of vasoactive medications (1.5 vs. 0.6 in those with controlled BP, p = 0.001). There were no significant differences related to kt/V, hematocrit, or weekly erythropoietin dose between patients with controlled or uncontrolled BP. Hemodialysis shift assignment (morning or afternoon) did not impact on BP levels or diurnal profile. Conclusion: In HD patients, interdialytic BP is often poorly controlled, there is a progressive rise in BP, and a trend toward loss of nocturnal decline in BP as the interdialytic period progresses. Further research is needed to determine whether treatment directed to interdialytic BP changes can alter outcomes in HD patients.

Sodium balance in maintenance hemodialysis.

Maintenance of extracellular fluid volume balance is an essential role of chronic maintenance hemodialysis (HD). In this population, this balance is determined by salt intake during the interdialytic period and sodium removal in HD sessions. Most of the sodium in a HD session is removed by ultrafiltration of plasma water, and the diffusion process becomes responsible for the fine tuning of sodium balance. The observation of little variation in pre‐HD serum sodium denotes that HD patients have an individual, stable osmolar set point. A positive dialysate‐to‐plasma sodium gradient is associated with increased thirst, interdialytic weight gain, and hypertension. To achieve an isonatric HD session, dialysate sodium concentration should approximately match patient’s serum sodium, and all sodium gained in the interdialytic period must be removed by convection. The pre‐HD serum sodium concentration may be used as a reference for dialysate sodium prescription in chronic HD. In this article, we also discuss new aspects of sodium balance, with particular attention to new observations on nonosmolar interstitial sodium storage.

Hypertension in dialysis.

Purpose of reviewHypertension is highly prevalent in dialysis patients and may be important to the high cardiovascular mortality of this population. This review shows the current direction in dialysis-associated hypertension management. Recent findingsDecreasing dialysate sodium concentration based on pre-hemodialysis plasma sodium concentration may have an additive effect in controlling hypertension. Sympathetic nervous system overactivity is an important feature of end-stage renal disease; a new amine oxidase, renalase, may be relevant to the pathogenesis of hypertension in this population. Similarly, drugs that block the sympathetic nervous system are uniformly protective in dialysis patients. Daily dialysis (short or long) results in better blood pressure control, and the mechanisms resulting in this effect are increasingly better understood. SummaryLong-term control of hypertension is necessary in dialysis patients. The better understanding of the dialysis-associated hypertension pathogenesis has impact on the dialysis prescription and antihypertensive drug choices. Abbreviations ABPM: ambulatory blood pressure monitoring; ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blocker; CREED study: Cardiovascular Risk Extended Evaluation in Dialysis Patients study; SNS: sympathetic nervous system.

Nitric Oxide, Malnutrition and Chronic Renal Failure

The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox). Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. Various studies document that markers of malnutrition and inflammation, such as low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are strong independent predictors of cardiovascular mortality in patients with end-stage renal disease (ESRD). There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L-arginine, ADMA and L-NMMA, which can inhibit NO synthesis and L-arginine transport, are increased whilst L-arginine is reduced in plasma from all stages of CRF patients. In this context, the uptake of L-arginine in blood cells is increased in undialysed CRF patients and in patients treated by CAPD and haemodialysis. In platelets obtained from haemodialysis patients, the activation of L-arginine transport and NO production was limited to well-nourished patients. Impairment in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in CRF and briefly describes possible therapeutic interventions.

Uremia, Atherothrombosis and Malnutrition: The Role of L-arginine- Nitric Oxide Pathway

The uraemic syndrome is a complex condition that results from an accumulation of multiple waste compounds, combined with failure of the endocrine and homeostatic functions of the kidney in end-stage chronic renal failure (CRF) patients. Recently it has become clear that uraemia is a microinflammatory condition with a significant increase in inflammation markers. Malnutrition is a common pathological condition which exacerbates cardiovascular mortality in uraemic patients. Inadequate diet and a state of persistent catabolism play major roles in uraemic malnutrition, yet the underlying mechanisms have not been completely clarified. Malnourished patients present elevated levels of circulating cytokines, further aggravating the oxidative and inflammatory characteristics of uraemia. It has been suggested that abnormalities in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in uraemia. Amongst the earliest indications of nutritional deficiency are low concentrations of plasma amino acids, including L-arginine, the precursor for nitric oxide (NO) synthesis. Atherosclerosis is an inflammatory disorder and NO is an important mediator of inflammation. There is a close association between thrombosis and platelet aggregation, and NO is involved in all stages of platelet activation. L-arginine inhibits platelet aggregation both in vitro and in vivo, while L-NMMA (NG-monomethyl-L-arginine), an endogenous L-arginine analogue and inhibitor of NO synthase (NOS), increases platelet activation and adhesion. The majority of studies in animal models and human patients indicate that the systemic production of NO is increased in uraemia. CRF patients show reduced plasma concentration of L-arginine, and the enhancement of L-arginine transport is essential to maintain increased NO synthesis in platelets taken from these patients. The present review provides an overview of recent advances in the understanding of the association among malnutrition, chronic inflammation and the L-arginine-nitric oxide pathway in uraemic patients, and related potential interventions that could improve clinical outcome in chronic renal failure.

How should we manage adverse intradialytic blood pressure changes

Variations in intradialytic blood pressure (BP) are a common and predictable occurrence in ESRD patients. These are caused by a decrease in blood volume provoked by ultrafiltration, lack of normal compensatory responses to fluid removal, underlying cardiac disease, and electrolyte changes that may adversely affect cardiovascular function. Intradialytic hypotension is the most frequent complication of the hemodialysis (HD) procedure and is fundamentally a consequence of an ultrafiltration rate that surpasses mechanisms activated to avert a decline in BP. Intradialytic hypertension is a less well-understood problem that has been recently associated with increased mortality. Fundamental patient characteristics and components of the HD procedure are involved in the pathophysiology of intradialytic hypotension and intradialytic hypertension. Correction of patient factors, modulation of HD prescription, and management of pharmacologic agents are the strategies to deal with adverse intradialytic BP changes.

Blood pressure management in hemodialysis: what have we learned?

Purpose of reviewTo review recent developments in the field of hypertension in hemodialysis patients. Recent findingsDespite the fact that hypertension is the most common complication of end-stage kidney disease, no evidence-based blood pressure (BP) targets exist for hemodialysis patients. There is growing evidence that outcomes are better predicted by out-of-office BP values, such as home or ambulatory BP monitoring. Intradialytic hypertension is associated with increased risk of death or hospitalization, and is probably mediated by volume overload. BP management should focus on volume control: dry weight ‘probing’ is well tolerated and effective in lowering BP, as are other strategies that minimize expansion of the extracellular fluid volume, such as avoidance of hypernatric dialysate. We discuss each of these issues in our review. SummaryModest advances in the understanding of hypertension have occurred in the past 2 years. Clinical trials that focus on BP targets and treatment choices are essential to guide future practice.