The prevalence of pulmonary hypertension is difficult to estimate. The vast majority of the studies assessing prevalence exclude patients who fit the first four categories of the World Health Organization Classification system, leaving only those with “unexplained pulmonary hypertension,” thereby underestimating the prevalence of PHT in the CKD V patient population. From a review of current series, the prevalence of unexplained pulmonary hypertension predialysis ranges from 0 to 39 %. For CKD V patients on HD, the prevalence of pulmonary hypertension ranges from 14 to 86 %, with most studies finding rates of approximately 40 %, and 0–68.8 % on peritoneal dialysis. The difference in prevalence may or may not be related to dialysis methodology, as the two populations are not necessarily similar, with peritoneal dialysis patients often being healthier and frequently younger than those on HD.

Pulmonary hypertension has been shown to increase in prevalence after the creation of AV access and is noted to regress after temporary access closure [40]. There is conflicting data as to whether blood flow rate directly correlates with PAP levels, with the majority suggesting that a higher flow rate is associated with pulmonary hypertension. However, pulmonary hypertension has also been shown to decrease after renal transplantation, even with continued presence of a functioning AV access with PAP decreasing from a mean of 49.8–38.6 (0.028) [41].

The pathogenesis of pulmonary hypertension in the CKD population is not clearly understood but appears to be multifactorial in nature. Factors that have been implicated include cardiac dysfunction, volume overload, high cardiac output often associated with increased pulmonary vascular resistance due to hormonal and metabolic derangement, uremic toxins, inflammation, endothelial dysfunction, pulmonary vascular calcification, embolization microbubble from dialyzer or particulate from access with resultant chronic hypoxia, and sleep apnea. PHT also has been shown to be present in CKD patients prior to the onset of dialysis at a higher rate than the normal population. In a study by Yang and Bao, of patients with CKD 1–3, they found 28.9 % of patients had a PASP of ≥35 [42]. In this predialysis group, BNP, left atrial diameter and GFR were independent determinants of pulmonary artery systolic pressure.

Dialyzer membrane utilized may play a role in the incidence and extent of pulmonary hypertension. Walker first assessed this in an animal model in 1984 [43]. More recently, Kiykim compared biocompatible and bioincompatible membranes and found that pulmonary artery pressure significantly decreased after dialysis with the high-flux polysulfone membranes, but not with the cellulose acetate membranes [44]. Patients with ESRD have acquired endothelial cell dysfunction, which reduces their ability to tolerate the elevated cardiac output associated with AV access creation. Havlucu and associates evaluated AVF flow by Doppler sonography and found a positive correlation with systolic pulmonary artery pressure and AV access flow rates [45]. Further, AVF compression decreased systolic pulmonary artery pressure from 36.8/10.7 to 32.8/10.5 mmHg. Hemodialysis and dry-weight reduction also decrease systolic pulmonary artery pressure. Nakhoul and coworkers studied the role of endothelin-1 and nitric oxide in the development of pulmonary hypertension after surgical access creation [41]. They found elevated endothelin levels in all dialysis patients, with 48 % of them having pulmonary hypertension. Those with pulmonary hypertension had a greater cardiac output than those without pulmonary hypertension. Hemodialysis increased nitric oxide metabolites in patients without pulmonary hypertension more than in those with PHT. Temporary closure of the access resulted in a transient decrease in cardiac output and systolic pulmonary artery pressure, suggesting that part of the mechanism of pulmonary hypertension may be related to the increased flow secondary to AV access. Harp and coworkers evaluated the relationship of access thrombectomy and pulmonary hypertension and found pulmonary hypertension in 52 % of all dialysis patients after at least one thrombectomy, versus 26 % in patients without thrombectomy [46]. Twenty-six percent of dialysis patients had either moderate or severe pulmonary hypertension, whereas in controls, the incidence of moderate to severe pulmonary hypertension was only 12 %. In patients with ESRD without thrombectomy, the prevalence of pulmonary hypertension was 42 %, with 14 % having moderate to severe hypertension. They concluded that thrombectomy was not a significant factor in pulmonary hypertension; however, the presence of ESRD was associated with a 2.7-fold increased risk of pulmonary hypertension. A study by Yigla and associates compared patients with long-term AV access, peritoneal dialysis patients, and those with chronic renal insufficiency [38]. Pulmonary hypertension was found in 37 % of AV access patients, in no peritoneal dialysis patients, and in one patient with renal insufficiency. Cardiac output was also found to be significantly higher—6.9 L/min versus 5.5 L/min—in patients on hemodialysis. Further, they found that pulmonary artery pressure increased in 66 % of patients after beginning hemodialysis. They concluded that both long-term hemodialysis and AV access creation appear to be associated with a high incidence of pulmonary hypertension by affecting pulmonary vascular resistance and cardiac output. Many authors have found a higher prevalence of pulmonary hypertension in patients with HD as compared to patients with peritoneal dialysis.

Treatment for pulmonary hypertension in ESRD patients

Treatment for pulmonary hypertension in ESRD patients requires accurate diagnosis of the etiology, as different causes require different therapies. The majority of this evaluation is not the purview of the vascular surgeon. Treatment includes right heart catheterization with vasoreactivity testing to determine etiology and permit focused therapy. Targeted therapy is indicated for those in Category I, while those in Category III require treatment of the underlying cause, i.e., COPD. Diuresis may be appropriate for Category II patients with CHF and may be appropriate in most CKD patients with ESRD. Treatment may include optimization of volume status and avoidance of peripheral vasodilators. Pharmacologic management, including anticoagulants, diuretics, digoxin, and oxygen, as well as calcium antagonists, is appropriate for many patients, as is exercise training therapy. Treatment of pulmonary hypertension associated with AV access can also include ligation of the access, distalization of the access to reduce flow, alternative modes of dialysis (e.g., peritoneal), or renal transplantation (Table 38.2).