Prospective observational studies have shown that arterial stiffness is a strong and independent predictor of cardiovascular disease in hemodialysis patients. Recent evidence further supports that arterial hardening predicts cardiovascular and all-cause mortality in peritoneal dialysis patients, renal transplant recipients and patients with chronic kidney disease (CKD) not on dialysis. Of note, dissociation of arterial stiffness with blood pressure reduction were related to worsened cardiovascular outcome in kidney disease patients, suggesting that arterial stiffness may not only be a predictor, but also a true risk factor, representing a specific and potentially reversible pattern of outward arterial remodeling in these individuals. On this basis, arterial stiffness has emerged as a novel therapeutic target for cardiovascular risk reduction in patients with CKD; specific interventions, such as renin-angiotensin-system blockade, use of statins, and decrease of calcium- phosphate product may delay the progression of arteriosclerotic process. This article summarizes the accumulated evidence from clinical and epidemiological studies regarding the prognostic significance of arterial stiffening on cardiovascular outcomes and provides insights on possible treatment strategies for arterial stiffness attenuation in patients with CKD.

Steroidal mineralocorticoid-receptor-antagonists (MRAs), such as spironolactone and eplerenone, are guideline-directed therapies in patients with heart failure with reduced ejection fraction or resistant hypertension. However, the associated risk of hyperkalemia and hormonal side effects limit their broad use and downstream cardiorenal protection in high-risk patients with type 2 diabetes mellitus (T2DM) and moderate-to-advanced chronic kidney disease (CKD). The critical unmet need to improve long-term cardiorenal outcomes in such patients with CKD has sparked considerable efforts to the discovery and development of a new class of compounds. Finerenone is a novel, nonsteroidal MRA that has recently received regulatory approval with the indication of cardiorenal protection in patients with CKD associated with T2DM. Two landmark phase 3 clinical trials, FIDELIO-DKD and FIGARO-DKD, demonstrated that among patients with T2DM and a broad spectrum of CKD, finerenone reduced the risk of “hard” cardiovascular and kidney failure outcomes as compared with placebo, with a minimal risk of hyperkalemia. Subgroup analyses of these trials also provided preliminary evidence that the efficacy and safety profile of finerenone was similar and irrespective of background therapy with other guideline-directed therapies, such as sodium-glucose co-transporter type 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists. Whether the combination of finerenone with a SGLT-2 inhibitor is more beneficial in patients with T2DM and CKD as compared with either therapy alone is a crucial research question that is currently under investigation in an ongoing clinical trial.

Arterial stiffness is typical feature of vascular remodeling in chronic kidney disease (CKD). Increased arterial stiffness raises flow and pressure pulsatility and is considered the principle pathogenic mechanism of isolated systolic hypertension, left ventricular hypertrophy, and congestive heart failure. Apart from the impact of arterial stiffness on left ventricular afterload, downstream transmission of pressure pulsatility to the level of microcirculation is suggested to promote injury of other susceptible organs. This may be of particular importance for kidney injury progression, since passive renal perfusion along with low resistance and input impedance in renal microvessels make kidneys particularly vulnerable to the damaging effect of systemic pulsatile pressure. Recent studies have provided evidence that arterial stiffness culminates in elevated pulsatility and resistance in renal microvasculature, promoting structural damage of small intra-renal arterioles. Further, prospective observational studies have shown that reduced aortic compliance is closely associated with the annual rate of renal function decline and represents independent predictor of kidney injury progression to end-stage renal disease among patients with CKD. This article provides insights into the cross-talk between macrocirculation and renal microcirculation and summarizes the currently available clinical evidence linking increased arterial stiffness with kidney disease progression.

Historically, eating during the hemodialysis treatment has been associated with increased risk for adverse intradialytic symptoms and events, risks that have resulted in the implementation of restrictive in-center nutrition policies. Recent studies, however, have recorded a shift in clinical practice with a higher proportion of physicians following the view that administration of intradialytic meals and supplements represents a simple and effective approach to enhance caloric intake and improve nutritional status among patients on hemodialysis. This shift towards less restrictive in-center nutrition practices is mainly supported by evidence from observational studies associating intradialytic nutritional supplementation with improvements in protein-energy wasting, inflammatory state, and health-related quality of life. In sharp contrast, earlier and recent interventional studies have documented that feeding during the hemodialysis treatment provokes a rapid postprandial decline in blood pressure and raises the incidence of symptomatic intradialytic hypotension. Furthermore, other studies have shown that postprandial redistribution in intravascular volume and enhanced blood supply to the gastrointestinal circulation may interfere with the adequacy of the delivered hemodialysis. Those who defend the position that intradialytic nutritional support is beneficial do not dispute the physiology of postprandial hemodynamic response, but they argue against its clinical significance. In this article, we provide an overview of studies that explored the effect of eating during the hemodialysis treatment on intradialytic hemodynamic stability and adequacy of the delivered hemodialysis. We reason that these risks have important clinical implications that are not counteracted by anticipated benefits of this strategy on caloric intake and nutritional status.

Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown. What distinguishes apparent treatment-resistance from true resistance is white-coat hypertension and adherence to medications. Accordingly, the diagnostic workup of a dialysis patient with apparent treatment-resistant hypertension on dialysis includes the accurate determination of BP control status with the use of home or ambulatory BP monitoring and exclusion of nonadherence to the prescribed antihypertensive regimen. In a patient on dialysis with inadequately controlled BP, despite adherence to therapy with maximally tolerated doses of a β-blocker, a long-acting dihydropyridine calcium channel blocker, and a renin-angiotensin system inhibitor, volume-mediated hypertension is the most important treatable cause of resistance. In daily clinical practice, such patients are often managed with intensification of antihypertensive therapy. However, this therapeutic strategy is likely to fail if volume overload is not adequately recognized or treated. Instead of increasing the number of prescribed BP-lowering medications, we recommend diet and dialysate restricted in sodium to facilitate achievement of dry weight. The achievement of dry weight is facilitated by an adequate time on dialysis of at least 4 hours for delivering an adequate dialysis dose. In this article, we review the epidemiology, diagnosis, and management of resistant hypertension among patients on dialysis.