Prior research indicates that hypertension in patients receiving hemodialysis is predominantly systolic, whereas isolated diastolic hypertension is rare and mainly affects younger patients. For a review published in Seminars
in Dialysis, we explored the role of volume overload, arterial stiffness, and erythropoietin use in the pathogenesis
of systolic versus diastolic hypertension among patients on hemodialysis.

In the Dry-weight Reduction in Hypertensive Hemodialysis Patients, or DRIP, trial, 150 hypertensive patients on
hemodialysis were randomized in a 2:1 ratio to ultrafiltration or control groups. The intervention in the ultrafiltration group was a gradual reduction in post-dialysis weight, whereas the control group received only usual care without any dry-weight adjustment. A reduction in post-dialysis weight by 0.9 kg at week 4 of follow-up resulted in a placebo-subtracted lowering of 6.9/3.1 mm Hg in 44-hour ambulatory blood pressure (BP). This BP-lowering effect persisted at 8 weeks followup. Since volume overload is an important mediator of systolic and diastolic BP elevation, the management of hypertension in hemodialysis should be initially relied upon strategies targeting
the achievement of an adequate dry-weight.

The association of arterial stiffness with ambulatory BP and its response to therapy were explored in a secondary analysis of the Hypertension in Hemodialysis Patients treated with Atenolol or Lisinopril, or HDPAL, trial. In adjusted analyses, each 1 m/sec higher aortic pulse wave velocity (PWV) was associated with 1.34 mm Hg greater 44-hour systolic BP and 1.02 mm Hg greater pulse pressure (PP), whereas the association of PWV with diastolic PP was not significant. Although baseline PWV was associated with an overall improvement in 44-hour PP, it was not a predictor of treatment-induced reduction in either 44-hour systolic or diastolic BP at 3, 6, and 12 months follow-up. Thus, a combined strategy of dry-weight reduction, sodium restriction, and antihypertensive drug use was effective in improving ambulatory BP control regardless of the severity of arteriosclerosis in the trial. Other non-volume-dependent mechanisms, such as erythropoietin use, may also be important mediators and should be taken into consideration, particularly in younger hemodialysis patients with diastolic hypertension. The exact magnitude and time course of the pressor effect induced by erythropoietin warrants further investigation in future clinical trials.