Table 3.

Pharmacologic therapy considerations for pulmonary arterial hypertension (Group 1 pulmonary hypertension) in CKD

Therapeutic class	Mechanism of action	Medication s	Clinical benefits	Adverse effects	CKD considerations
Endothelin receptor antagonists	Blocks ET-1 binding to its receptors, inhibiting pulmonary vasoconstriction and vascular SMC proliferation	Bosentan, ambrisentan, macitentan	Improved dyspnea and exercise capacity	Liver toxicity, peripheral edema, anemia	-Could worsen pre-existing peripheral edema -No dosage adjustment needed
Prostacyclin pathway agonists	Activates prostacyclin signaling, causing vascular smooth muscle relaxation, reduction of SMC proliferation, and inhibition of platelet aggregation	epoprosteno I, treprostinil, iloprost, selexipag	Improved survival (with continuous IV infusion), exercise capacity, dyspnea, quality of life	Flushing, tachycardia, diarrhea, nausea, headaches, pain; sepsis, hemorrhage, pulmonary embolism with IV infusions	-Catheter-related issues with IV preparations may add risk in dialysis; -chronic pain and nausea are common in CKD -No dosage adjustment needed, except for iloprost, which has decreased clearance in kidney failure, 50% decrease in initial dose has been recommended
Nitric oxide pathway enhancers	Increases vascular SMC cGMP concentrations, causing vasodilation and antiproliferation	PDE5 inhibitors: sildenafil, tadalafil, vardenafil; guanylate cyclase stimulant: riociguat	PDE5 inhibitors: improved survival and exercise capacity; guanylate cyclase stimulant: improved functional class, possibly exercise capacity	Headache, Gl upset, myalgias, flushing, dizziness, hemoptysis with guanylate cyclase stimulant; hypotension if combined with nitrates	-Sildenafil: no adjustment in CKD or dialysis -Tadalafil: avoid use if CLcr < 30 ml/min or HD; start at 50% usual dose for CLcrl 30–80 ml/min -vardenafil: avoid use in dialysis -riociguat: not recommended if CLcr < 15 ml/min

IV : intravenous; cGMP: cyclic guanosine monophosphate; I: gastrointestinal; CLC_cr: creatinine clearance; ET-1, endothelin 1; IV, intravenous; SMC, smooth muscle cell