Assessment and Management of Hypertension among Patients on Peritoneal Dialysis

Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population

Con: Nutritional vitaminDreplacement in chronic kidney disease and end-stage renal disease

Insufficiency of 25-hydroxyvitamin D [25(OH)D] is highly prevalent among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) and is a critical component in the pathogenesis of secondary hyperparathyroidism. Accordingly, current National Kidney Foundation—Kidney Disease Outcomes Quality Initiative and Kidney Disease: Improving Global Outcomes guidelines recommend the correction of hypovitaminosis D through nutritional vitamin D replacement as a first-step therapeutic approach targeting secondary hyperparathyroidism. In this Polar Views debate, we summarize the existing evidence, aiming to defend the position that nutritional vitamin D replacement is not evidence-based and should not be applied to patients with CKD. This position is supported by the following: (i) our meta-analysis of randomized controlled trials shows that whereas nutritional vitamin D significantly increases serum 25(OH)D levels relative to placebo, there is no evidence either in predialysis CKD or in ESRD that parathyroid hormone (PTH) is lowered; (ii) on the other hand, in randomized head-to-head comparisons, nutritional vitamin D is shown to be inferior to activated vitamin D analogs in reducing PTH levels; (iii) nutritional vitamin D is reported to exert minimal to no beneficial actions in a series of surrogate risk factors, including aortic stiffness, left ventricular mass index (LVMI), epoetin utilization and immune function among others; and (iv) there is no evidence to support a benefit of nutritional vitamin D on survival and other ‘hard’ clinical outcomes. Whereas nutritional vitamin D replacement may restore 25(OH)D concentration to near normal, the real target of treating vitamin D insufficiency is to treat secondary hyperparathyroidism, which is untouched by nutritional vitamin D. Furthermore, the pleotropic benefits of nutritional vitamin D remain to be proven. Thus, there is little, if any, benefit of nutritional vitamin D replacement in CKD

Revisiting RAAS blockade in CKD with newer potassium-binding drugs

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials

Blood pressure in hemodialysis: targets?

Purpose of review In the absence of ‘hard’ clinical-trial evidence to define optimal blood pressure (BP) targets and validate different BP measurement techniques, management of hypertension in hemodialysis is based on expert opinions. In this review, we provide a comparative evaluation of out-of-dialysis BP monitoring versus dialysis-unit BP recordings in diagnosing hypertension, guiding its management and prognosticating mortality risk. Recent findings Owing to their high variability and poor reproducibility, predialysis and postdialysis BP recordings provide inaccurate reflection of the actual BP load outside of dialysis. Contrary to the reverse association of peridialytic BP with mortality, elevated home and ambulatory BP provides a direct mortality signal. Out-of-dialysis BP monitoring, even when done in the clinic, is a reliable approach to manage hypertension in the dialysis unit. Whenever none of these measures are available, median intradialytic SBP can provide a better estimate of interdialytic BP levels compared with peridialytic BP measurements. Summary Although out-of-dialysis BP monitoring have better diagnostic accuracy and prognostic validity, randomized trials are needed to ascertain BP targets for managing hypertension in hemodialysis patients

Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide

Objective: Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide. Research design and methods: PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP. Results: We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality. Conclusions: This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide

Blood pressure control in conventional hemodialysis

Hypertension among patients on hemodialysis is common, difficult to diagnose and often inadequately controlled. Although specific blood pressure (BP) targets in this particular population are not yet established, meta-analyses of randomized trials showed that deliberate BP-lowering with antihypertensive drugs improves clinical outcomes in hemodialysis patients. BP-lowering in these individuals should initially utilize nonpharmacological strategies aiming to control sodium and volume overload. Accordingly, restricting dietary sodium intake, eliminating intradialytic sodium gain via individualized dialysate sodium prescription, optimally assessing and managing dry-weight and providing a sufficient duration of dialysis are first-line treatment considerations to control BP. If BP remains uncontrolled despite the adequate management of volume, antihypertensive therapy is the next consideration. Contrary to nonhemodialysis populations, emerging clinical-trial evidence suggests that among those on hemodialysis, β-blockers are more effective than agents blocking the renin-angiotensin-system (RAS) in reducing BP levels and protecting from serious adverse cardiovascular complications. Accordingly, β-blockade is our first-line approach in pharmacotherapy of hypertension. Long-acting calcium-channel-blockers and RAS-blockers are our next considerations, taking into account the comorbidities and the overall risk profile of each individual patient. Additional research efforts, mainly randomized trials, are clearly warranted in order to elucidate aspects of management that remain elusive in hypertensive dialysis patients

Cardiorenal protection in advanced chronic kidney disease: research highlights from landmark papers published in Nephrology Dialysis Transplantation during 2018

Chronic kidney disease (CKD) and cardiovascular disease go hand-in-hand and an inverse, strong and independent relationship exists between estimated glomerular filtration rate (eGFR) and the risk of cardiovascular morbidity and mortality [1, 2]. In fact, the mortality hazard attributable to CKD is even higher than the mortality risk arising from diabetes mellitus (DM) and comparable with that of established coronary artery disease, thus CKD is considered a coronary disease equivalent [3]. The burden of cardiovascular disease, particularly due to heart failure or the development of cardiac arrhythmias, is multiplied in those with end-stage renal disease (ESRD) on chronic dialysis. It has to be noted, however, that clinical trial evidence to guide the management of cardiovascular disease in these high-risk patients is scant [4]. This lack of evidence is at least partly attributable to the fact that advanced CKD/ESRD was systematically an exclusion criterion in the majority of large outcome trials that have demonstrated the safety and efficacy of several cardioprotective therapies in earlier stages of CKD or in the general population [4]. In this editorial we discuss therapeutic strategies to optimize cardiovascular and/or renal protection in advanced CKD based on research highlights from ‘landmark’ papers published in Nephrology Dialysis Transplantation during 2018. We provide ‘take-home messages’ from these studies and directions for future research in these important areas

The Effect of Convective Dialytic Modalities on Arterial Stiffness in End-Stage Renal Disease Patients

Among end-stage renal disease (ESRD) patients receiving hemodialysis, increased arterial stiffness is an independent cardiovascular risk predictor. Over the past few years, arterial stiffness attenuation has been increasingly recognized as a novel therapeutic target toward cardiovascular risk reduction in the dialysis population. Structural alterations related to the long-term arteriosclerotic process are difficult to modify; with the exception of blood pressure (BP)-lowering, there are no other therapeutic interventions with well-documented benefits in delaying the progression of arteriosclerosis among dialysis patients. Enhanced clearance of middle-to-high molecular weight solutes by combining convective and diffusive transport through hemodiafiltration and the associated benefits on microvascular endothelial function have generated the hypothesis that convective dialytic modalities may be advantageous in improving large-artery stiffness. This notion is supported by some clinical studies showing that switching ESRD patients from low-flux hemodialysis to high-efficiency on-line hemodiafiltration was associated with significant reduction in arterial stiffness. These beneficial effects, however, were not confirmed in a recent subanalysis of the CONvective TRAnsport STudy (CONTRAST) trial. In this chapter, we summarize the currently available evidence on the effect of hemodiafiltration versus hemodialysis on arterial stiffness, discussing also the potential clinical implications of this effect

RAAS Blockade as First-Line Antihypertensive Therapy among People with CKD

Hypertension among people with chronic kidney disease is highly prevalent and remains often poorly controlled. To adequately control blood pressure (BP), a combination antihypertensive drug therapy is often required. The choice of the appropriate antihypertensive regimen should be individualized according to the patient clinical characteristics, the severity of chronic kidney disease (CKD), the levels at which BP should be targeted and the presence or absence of proteinuria. In proteinuric CKD, solid evidence from large-scaled randomized trials suggest that agents blocking the renin-angiotensin-aldosterone system (RAAS) should be the antihypertensive therapy of first choice, given their superiority over the other antihypertensive drug classes in reducing proteinuria and delaying nephropathy progression to end-stage-renal-disease (ESRD). In contrast, inhibition of the RAAS is shown to have no additional benefits towards renoprotection in people with non-proteinuric CKD. Combined RAAS blockade as an alternative approach to gain additive reduction in proteinuria and greater retardation of renal function decline is shown to be associated with increased risk of hypotension, serious hyperkalemia and acute kidney injury. In this chapter, we discuss the role of RAAS blockade as first-line antihypertensive therapy among people with proteinuric and non-proteinuric nephropathy, providing an overview of the evidence derived from large-scaled renal outcome trials