Version May 2024
INTRODUCTION — Pulmonary hypertension (PH) in patients with end-stage kidney disease (ESKD) is a serious condition that is associated with an increased risk of cardiovascular events and death [1-6]. Identifying PH can be challenging but is important in this population since management strategies differ from those for patients with ESKD who do not have PH.
The presentation, diagnosis, and management of patients with ESKD and PH is presented in this topic review. The evaluation and management of PH in other populations are discussed separately:
●(See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)
●(See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)
●(See "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults".)
DEFINITION — PH is a chronic progressive disease characterized by an elevated pulmonary arterial pressure. While there is no specific hemodynamic cutoff used to define PH in patients with ESKD, we typically consider a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg at rest as elevated [7].
INCIDENCE — The true incidence of PH in patients with ESKD is unknown since most studies report incidence rates based upon echocardiographic data and variable criteria. Nonetheless, rates of PH appear to be higher in patients with ESKD compared with the general population (approximately 10 percent in the latter) and vary depending upon the stage of kidney disease and type and vintage of dialysis.
As examples, rates have been cited as the following:
●Patients with stage 5 chronic kidney disease (CKD) – 9 to 39 percent [8].
●Patients undergoing hemodialysis – 19 to 69 percent [9,10].
●Patients undergoing peritoneal dialysis – 13 to 19 percent [8,11-13].
PH rates rise as kidney failure progresses and may increase over time for those on dialysis. In one study, rates of PH in patients with nondialysis CKD rose with disease stage (stage 3 [22 percent], stage 4 [24 percent], and stage 5 [32 percent]) [14]. Another retrospective study reported an increasing incidence of PH over time among those on dialysis (dialysis <1 year [25 percent], dialysis 1 to 2 years [38 percent], and dialysis >2 years [58 percent]) [15].
Incidence rates may be lower than those reported in echocardiographic studies when the diagnostic gold standard, right heart catheterization (RHC), is used to detect PH.
In one study, among 31 patients undergoing hemodialysis, RHC identified PH in 78 percent, the majority of whom had postcapillary PH (65 percent; ie, PH associated with increased left-sided cardiac filling pressures, group 2 PH) and a minority of whom had precapillary PH (13 percent; ie, group 1 pulmonary arterial hypertension) (table 1) [16]. Among 31 patients who had not yet started hemodialysis, postcapillary PH was diagnosed in 71 percent, and precapillary PH was detected in 6 percent. The prevalence of precapillary PH may be higher than would be expected in the general population [17-19].
No sex or racial predilection for PH in patients with ESKD has been described.
CLASSIFICATION AND PATHOGENESIS — A five-group classification system categorizes PH based on similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management (table 2) [7]:
●Group 1 – Pulmonary artery hypertension (PAH)
●Group 2 – PH due to left heart disease
●Group 3 – PH due to lung diseases and/or hypoxia
●Group 4 – PH due to pulmonary artery obstructions (eg, chronic thromboembolic disease)
●Group 5 – PH with unclear and/or multifactorial mechanisms
The term PAH is used for group 1 disease while PH is used for all others. PH that occurs in patients with ESKD is typically classified as group 5 PH (table 3) since there is no single unifying mechanism that explains the pathogenesis of PH in this population. However, some patients may be partially or completely classified into another group, provided they meet select criteria for that group. Further details on classification are provided separately. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Postdiagnostic testing and classification'.)
As a multifactorial disorder, several pathogenetic factors have been implicated in the development of PH in patients with ESKD. These include the following:
●High prevalence of comorbidities associated with PH – In patients with ESKD, there is a high prevalence of comorbidities, particularly cardiac disease, that potentially contribute to the higher than usual prevalence of PH in this population. However, their contribution to and pathogenetic role in the development of actual PH are unclear. As examples:
•There is a high prevalence of heart failure among patients with ESKD (30 to 77 percent) [20-25] and consequently a high incidence of group 2 PH [16]. (See "Overview of screening and diagnosis of heart disease in patients on dialysis".)
•Patients with connective tissue disease (CTD) may have both CTD-PAH and chronic kidney disease (CKD) [26].
•Pulmonary and sleep disorders often coexist with CKD (ranging from 17 to 53 percent of patients with ESKD) [27-35]. (See "Sleep disorders in end-stage kidney disease".)
•There is an increased prevalence of thromboembolic disease in patients with ESKD [36-38] although recurrent embolization from repeated arteriovenous (AV) access thrombectomies does not appear to be a risk factor for the development of PH in this population [37-39].
●Role of arteriovenous (AV) access flow – AV access flow has been implicated as a contributing factor to the development of PH in patients with ESKD on dialysis. However, it is unlikely that AV access is a stand-alone factor for the development of PH.
The role of AV access flow in the development of PH is considered most likely due to increased vascular flow in the setting of altered cardiovascular physiology or pathology, and hormonal and metabolic alterations of ESKD. As an example, the increase in cardiac output following access creation is accompanied by an increase in pulmonary arterial pressure [1,40-44]. The change directly correlates with the blood flow through the AV access [2,45-47] and can be attenuated or resolve in some patients by AV access compression or closure [2,12,41,48,49]. Increased AV flow over time during dialysis may also contribute to the increased risk of developing PH while on dialysis [16].
●Fluid overload – Fluid overload has been implicated in the development of ESKD-related PH (ESKD-PH). Evidence to support this theory includes the observation that PH may improve following ultrafiltration [50] or successful kidney transplantation [51] (usually by improving cardiac function) and the known effects of chronic increased flow through the pulmonary vascular bed in the development of pulmonary arterial hypertension. (See "The epidemiology and pathogenesis of pulmonary arterial hypertension (Group 1)", section on 'General physiologic mechanisms'.)
●Endothelial dysfunction – Endothelial dysfunction in patents with ESKD has also been implicated in the development of PH [52-57]. Endothelial dysfunction leads to an impaired capacity of the endothelium to regulate vascular tone mediated by nitric oxide (NO). Reduced levels of NO have been reported in patients on hemodialysis with PH compared with those without PH, and hemodialysis treatment results in greater posttreatment elevations of NO in those without versus with PH [58].
The major contributor to reduced levels of NO in CKD is asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase [59]. This compound accumulates in CKD and negatively correlates with glomerular filtration rate (GFR) [60-62]. ADMA levels are elevated in patients with early phases of kidney disease, even before GFR is significantly reduced [63]. Both ADMA and the vasoconstrictor endothelin-1 have been shown to be significantly elevated in patients with predialysis ESKD [15,64].
●Miscellaneous – Other factors that have been cited as possibly playing a role in the development of PH in patients with ESKD include the following:
•Pulmonary vascular calcification [65,66]. (See "Vascular calcification in chronic kidney disease".)
•Neutrophil activation related to exposure to bioincompatible dialysis membranes [9].
CLINICAL FEATURES — The symptoms and signs of PH in patients with ESKD are the same as in those without ESKD (eg, progressive dyspnea, fatigue, syncope, signs of right heart failure). Similar to PH associated with other etiologies, PH in patients with ESKD is progressive and may only be suspected when PH progresses in severity and right heart failure develops. Further details regarding the clinical presentation of PH are provided separately. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Clinical manifestations'.)
DIAGNOSIS AND EVALUATION — Patients with ESKD and suspected PH should be co-evaluated by experts in nephrology and PH.
When to suspect PH in ESKD — In patients with end-stage kidney disease (ESKD), we maintain a high index of suspicion for pulmonary hypertension (PH) since the symptoms of volume overload (eg, dyspnea, edema, elevated jugular venous pressure) overlap with those of PH.
Useful clues that may suggest PH in patients with ESKD include the following:
●Symptoms of heart failure that are resistant to maximal medical management.
●A tricuspid insufficiency murmur in the absence of a cardiac rhythm device with transvenous leads [17,67].
●Electrocardiographic and/or echocardiographic evidence of right ventricular hypertrophy [17], although a normal electrocardiogram or echocardiography does not exclude PH.
●Worsening symptoms within days to weeks following arteriovenous (AV) access placement.
●Poor tolerance of ultrafiltration in patients with dyspnea and hypervolemia.
Initial diagnostic evaluation — Evaluation and diagnosis of PH in patients with ESKD are similar to those for patients without ESKD (algorithm 1). We typically begin with transthoracic echocardiography (TTE), a search for common etiologies associated with PH, and the selective performance of right heart catheterization (RHC) to confirm or exclude PH. This evaluation is discussed separately. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Initial diagnostic evaluation (noninvasive testing)'.)
In our experience, RHC is often needed in this population since RHC can distinguish precapillary from postcapillary disease (table 1), differentiate high-output from low-output heart failure, and determine whether PH is multifactorial in nature. In addition, RHC may provide therapeutic information in patients with an AV access when the response to manual compression is needed. Importantly, hemodynamic and other forms of testing should ideally be performed in the euvolemic state based upon an accurate assessment of the patient's dry weight. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Right heart catheterization'.)
Establishing the diagnosis — The diagnosis of ESKD-PH is ideally made based on RHC that demonstrates an elevated mean pulmonary artery pressure >20mmHg. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Diagnosis'.)
However, in some patients, the diagnosis of PH is made clinically, using a constellation of findings and noninvasive testing, typically echocardiography (eg, patients with mild symptoms who clearly have group 2 or 3 PH). (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Diagnosis' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Group 2: PH due to left heart disease' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Group 3: PH due to chronic lung disease and/or hypoxemia'.)
Classification and assessment of arteriovenous access contribution — The postdiagnostic evaluation with ESKD-PH involves appropriately classifying the patient (table 2) by assessing the potential contribution of existing comorbidities and/or precapillary disease to PH.
Allocation of classification is important since, in general, only patients with pulmonary arterial hypertension (PAH; ie, group 1) are eligible for PAH-specific therapies (eg, pulmonary vasodilators) outside of the research trial setting. Assigning a classification generally involves evaluating available data, performing additional testing if needed, and obtaining the opinion of both the PH and nephrology expert. As an example, a patient with mild (CKD) due to scleroderma and no arteriovenous (AV) access who has classic findings of precapillary disease on RHC may be appropriately allocated into group 1 and may qualify for PAH-specific therapies. By contrast, a patient with ESKD who has components of both precapillary and postcapillary disease and who has known cardiopulmonary disease may be more appropriately classified as group 5 (ie, multifactorial and is not likely to qualify for PAH-specific therapy outside of a research setting). Further details regarding the diagnosis of PH and postdiagnostic testing for appropriate classification are provided separately. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Diagnosis'.)
Additional postdiagnostic evaluation in select patients with ESKD who are on hemodialysis, involves assessing the relationship of AV access flow to PH (eg, patients with mild to moderate symptoms who are being evaluated for a flow reduction procedure). This can be determined by measuring pulmonary pressures before and after manually compressing the AV access. This maneuver may help predict whether banding/plication of the AV access may improve PH.
In our clinical experience, the contribution of AV flow to PH can be assessed by manually compressing the AV access under therapeutic heparinization and a tourniquet set to at least 30 mmHg above systolic blood pressure for one minute while measuring pulmonary hemodynamics on RHC. If a significant component of the patient's PH is related to the AV access, pulmonary hemodynamic measurements should fall significantly [2]. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Right heart catheterization'.)
However, the definition of what constitutes a significant decrease is not established and is highly subjective. We consider a significant decrease as a reduction by at least 20 percent or more or normalization of the mean pulmonary artery pressure and right atrial pressure (and possibly the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure) when the AV access is compressed [2,68].
While there is concern that compression of an AV access could lead to thrombosis (particularly if the access is an AV graft), in practice, this complication is rare, especially if the patient is systemically heparinized prior to AV access compression. Management of the thrombosed AV access is reviewed separately. (See "Hemodialysis arteriovenous graft dysfunction and failure", section on 'Treatment of thrombosis' and "Failure of the mature hemodialysis arteriovenous fistula", section on 'Thrombosed fistula'.)
Differential diagnosis — For patients with symptoms in whom PH is suspected, the differential diagnosis includes a wide spectrum of cardiopulmonary and other disorders, most of which are distinguished by routine investigations performed for PH. Further details regarding this differential are provided separately. (See "Approach to the patient with dyspnea" and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Initial differential diagnosis'.)
The differential diagnosis of dyspnea and intradialytic hemodynamic instability includes heart failure and ischemic heart disease, which can be distinguished by TTE or stress testing. (See "Intradialytic hypotension in an otherwise stable patient", section on 'Second-line approach'.)
MANAGEMENT — For patients with ESKD-PH, we follow the same basic principles of management as for other patients with PH. Patients should be comanaged by clinicians who have expertise in ESKD as well as clinicians with expertise in PH. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)
The major focus of management involves the following (algorithm 2):
●Reducing volume overload and left-sided heart pressures (since a sizeable proportion of patients with ESKD-PH have left ventricular systolic and/or diastolic dysfunction that contributes to PH). (See 'General measures in all patients' below and 'Volume management' below and 'Classification and pathogenesis' above.)
●Planning a dialysis modality for those with PH who are not yet on dialysis. (See 'Predialysis patients' below.)
●Managing dialysis access and therapy for those who are diagnosed while on dialysis. (See 'Patients on hemodialysis' below.)
●Regardless of dialysis modality and access, patients with ESKD-PH, particularly those with arteriovenous (AV) access, need close monitoring for deterioration of PH. (See 'Monitoring for PH' below.)
General measures in all patients — These include the following:
●Routine pulmonary and PH care – Patients with ESKD-PH should exercise as tolerated, receive routine vaccinations (figure 1), be counselled against smoking and vaping, and maintain a normal body mass index. When indicated, they should also be treated with oxygen and diuretics (when feasible).
We do not typically anticoagulate this population unless another indication is present (eg, atrial fibrillation).
Females of childbearing age should be counselled regarding the risks of pregnancy.
Such general measures are similar to those in patients with PH and are discussed separately. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)", section on 'General measures and supportive therapy'.)
●Routine kidney disease care – Other routine aspects of kidney disease care, including management of systemic hypertension, anemia, and chronic kidney disease (CKD)-mineral and bone disorder, may take on even more importance for prevention and management of PH, but there is no evidence to guide specific management alterations in PH. (See "Overview of the management of chronic kidney disease in adults".)
We typically manage volume aggressively. The principles of dialysis management are discussed below. (See 'Volume management' below and 'Patients on peritoneal dialysis' below.)
●Optimizing therapy for comorbidities – We optimize therapies for any comorbidities known to be associated with or worsen PH, particularly heart failure, obstructive sleep apnea, and underlying lung disease, all of which are common in patients with ESKD. Volume management is particularly important in those with group 2 PH and group 5 PH (table 2). (See "Overview of the management of heart failure with reduced ejection fraction in adults" and "Obstructive sleep apnea: Overview of management in adults" and "Pulmonary hypertension due to left heart disease (group 2 pulmonary hypertension) in adults", section on 'Optimized management of left heart disease'.)
Dialysis management — The approach to dialysis management in patients with ESKD depends upon whether the patient is predialysis or already receiving dialysis. Because AV access flow can impact cardiopulmonary hemodynamics, access flow volume must be a consideration in dialysis access planning and management. Access flow monitoring and measurement are reviewed separately. (See "Clinical monitoring and surveillance of the mature hemodialysis arteriovenous fistula", section on 'Intra-access flow rate' and "Clinical monitoring and surveillance of hemodialysis arteriovenous grafts to prevent thrombosis", section on 'Intra-access blood flow monitoring' and "High-flow hemodialysis arteriovenous access", section on 'Access flow measurement'.)
Predialysis patients — Because high flow through an AV access can contribute to the development of PH in patients with ESKD, we evaluate predialysis patients for the presence of PH as part of dialysis access planning. The presence of PH should influence the selection of dialysis modality and, for those who will undergo hemodialysis access selection. The recommended approach for the patient is as follows:
●For patients with preexisting PH who are being considered for maintenance dialysis, we suggest peritoneal dialysis (PD) rather than hemodialysis (HD) as the choice of dialysis modality. This preference is clear for patients who are symptomatic; however, no evidence-based criteria are available to guide planning in patients with asymptomatic PH who are being considered for dialysis such that clinical judgment is necessary for the latter. Factors that weigh into the decision to perform PD are complex and are discussed separately. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality", section on 'Available modalities'.)
Our preference for PD is based upon the rationale that PD obviates the need for AV access, thereby eliminating increases in blood flow that could worsen PH. In addition, PD provides daily ultrafiltration that may prevent interdialytic volume overload that can be seen with HD.
●For most patients with PH who are not suited to, decline, or fail PD, we evaluate for HD. We prefer using a low-flow AV access (such as a radial-cephalic AV fistula) for HD as this option may be sufficient to provide adequate flow for effective dialysis while limiting the impact of AV flow on worsening PH. This must be balanced, however, against the likelihood that a low-flow AV access may not have sufficient flow for hemodialysis. However, if the patient has a limited life expectancy (ie, months), we perform dialysis using a hemodialysis catheter [69]. While this option eliminates the impact of AV flow on PH, it is not suitable for long-term hemodialysis. (See "Approach to the adult patient needing vascular access for chronic hemodialysis".)
Patients on hemodialysis — For patients receiving hemodialysis who have PH, we treat patients with aggressive volume management and address AV access issues that may be contributing to PH.
Volume management — We manage patients with ESKD-PH who are on hemodialysis with aggressive removal of volume. We maintain the estimated dry weight as low as possible without causing intra- or interdialytic hypotension. This may require changes in the dialysis prescription to provide longer or more frequent dialysis sessions to safely achieve a lower dry weight (eg, daily sessions). (See "Intradialytic hypotension in an otherwise stable patient", section on 'Prevention of recurrent episodes'.).
AV access management — In general, for patients on hemodialysis, the arteriovenous (AV) access is managed according to the severity of symptoms and the level of flow through the AV access. (See "High-flow hemodialysis arteriovenous access", section on 'Access flow measurement'.)
●Severe symptoms – For patients with severe symptoms (eg, New York Heart Association class III/IV (table 4)), the AV access generally requires ligation regardless of the measured volume of flow. The patient should ideally be converted to peritoneal dialysis, if possible, or to hemodialysis using a tunneled hemodialysis catheter [70]. (See "High-flow hemodialysis arteriovenous access", section on 'AV access ligation'.)
●Mild to moderate symptoms – For patients with mild to moderate symptoms (eg, New York Heart Association class I to II) who have either high-flow AV access (ie, flow ≥1500 mL/min [71-75]) or moderate flow (800 to 1500 mL/min) and significant reduction in pulmonary pressures with AV access compression (see 'Classification and assessment of arteriovenous access contribution' above), we suggest a flow reduction procedure rather than observation. For all other patients with mild to moderate symptoms, AV access management is uncertain and should be individualized and agreed upon by experts and the patient. As an example, a flow reduction procedure may be considered in a patient with high flow and minimal or no response to manual compression, although outcomes are unknown in this subgroup. Alternatively, observation with a view to having a low threshold for flow reduction may also be appropriate (eg, patient with normal AV flow).
The goal of flow reduction procedures is to decrease flow to suggested levels of 800 mL/min for an AV fistula and 1000 mL/min for an AV graft in a patient with a normal blood pressure [76,77]. To achieve effective hemodialysis while improving PH, the AV access flow should be reduced to levels no lower than 500 to 600 mL/min for AV fistulae and 600 to 700 mL/min for AV grafts. (See "High-flow hemodialysis arteriovenous access", section on 'Flow reduction' and "Hemodialysis access-induced distal ischemia", section on 'Precision banding'.)
After flow reduction, close patient follow-up to determine the course of the patient's symptoms (eg, dyspnea, edema) is important. Pulmonary pressures should decrease following either flow reduction or access ligation. However, the response is variable depending upon the etiology of PH. In cases with predominantly postcapillary PH, pulmonary pressures should fall as soon as cardiac pressures decrease. In those with predominantly precapillary PH, the response may be minimal, if any. Nevertheless, the beneficial effect of flow reduction on cardiac output should slow the rate of PH progression.
●If symptoms improve, the patient should continue to be monitored. The interval for evaluation should be determined by the patient's individual situation. (See 'Monitoring for PH' below.)
●If symptoms do not improve after flow reduction, we repeat echocardiography and right heart catheterization, and if symptoms are due to worsening PH, the access should be ligated. Peritoneal dialysis should be initiated, if feasible. If hemodialysis is to be continued, a tunneled hemodialysis catheter should be placed. (See 'Patients on peritoneal dialysis' below.)
Patients on peritoneal dialysis — Similar to patients with ESKD-PH on hemodialysis, patients with ESKD-PH on peritoneal dialysis should be managed with aggressive removal of volume to maintain an estimated dry weight as low as possible without causing intra- or interdialytic hypotension. The issues with access blood flow that are relevant to patients on hemodialysis do not apply to those on peritoneal dialysis. (See 'Volume management' above.)
For most patients with PH who are not suited to, decline, or fail PD, and in whom dialysis is needed long term, HD using a low-flow AV access (such as a radial-cephalic AV fistula) is an option. (See "Evaluating patients for chronic peritoneal dialysis and selection of modality", section on 'Available modalities'.)
Monitoring for PH — Pulmonary hypertension (PH) is progressive regardless of the chosen dialysis modality, access management, and supportive therapy for underlying disorders. Although there is no consensus, we clinically monitor all patients with ESKD-PH for worsening symptoms of PH at every dialysis treatment, particularly after creation of an AV access, initiation of dialysis, and following ligation or flow reduction procedures. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Clinical manifestations'.)
●For those with known PH who have symptoms that do not improve or progress despite dialysis or aggressive ultrafiltration, we often repeat echocardiography and/or a right heart catheterization (RHC) and AV compression and flow studies to evaluate for progressive disease. (See 'Initial diagnostic evaluation' above and 'Patients on hemodialysis' above.)
●For patients with preexisting PH who do not worsen after dialysis or AV access placement, we typically obtain periodic echocardiograms, the frequency of which is based upon clinical judgment (eg, every one to two years in stable patients or at one to two months after AV access creation) to reassess heart size, function, and pulmonary hemodynamics, although the value of this approach is unproven.
Refractory disease — Patients with persistent, severe PH (eg, severe symptoms and/or mean pulmonary arterial pressure [mPAP] greater than 35 mmHg) despite dialysis and AV fistula management should be referred to centers with expertise in the management of PH for possible evaluation in trials of PH-specific therapy [8]. (See "Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy".)
There is a paucity of data describing the impact of PH-specific therapy in ESKD-PH [19,78]. One retrospective study of 18 patients on dialysis for ESKD, most of whom had scleroderma-associated PH (and kidney disease) or chronic thromboembolic PH (ie, group 1 and 4 PH (table 2)), described successful treatment of PH with PH-specific therapy [19]. Hypotension was common as an adverse effect.
KIDNEY TRANSPLANTATION — Among patients with ESKD who are being evaluated for kidney transplantation, the presence of moderate to severe pulmonary hypertension may affect their transplant candidacy. Severe pulmonary hypertension has been associated with decreased posttransplant survival and, among recipients of a deceased-donor kidney, an increased risk of early kidney allograft dysfunction. Lowering the mean pulmonary artery pressure before transplant can be challenging and involves a combination of aggressive fluid management, fistula flow control, and in some cases, pulmonary arterial hypertension therapies, when indicated. These issues are discussed in more detail elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Pulmonary disease'.)
PROGNOSIS — In patients with ESKD, PH is an independent predictor of cardiovascular events and mortality [2-5,79,80]. This is true for both patients with predialysis chronic kidney disease (CKD) and those on dialysis:
●In a study of patients with CKD stage 3 through 5, a cardiovascular event occurred more frequently among patients with PH compared with those without PH (48 versus 21 percent, respectively) over a median of 22 months [14]. The most common event was acute decompensated heart failure (25 percent), followed by stroke (20 percent) and cardiac arrest (12 percent). Higher mortality was also noted in patients with PH (29 versus 17 percent).
●In a study of patients on dialysis, those with PH had a higher mortality compared with those without PH (31 versus 4 percent) [2]. Other observational studies have also reported similar findings [6,45].
The impact of preexisting PH on allograft function after kidney transplant is unclear. In one retrospective study, pretransplant PH was associated with a higher rate of graft failure compared with patients without PH who underwent kidney transplant [81]. In contrast, another retrospective study described no difference in allograft survival between those with or without PH [82]. However, the varying definition and tests used to measure PH in this population may influence the accuracy of prognostic studies.
Although rare, PH may predispose a patient to the development of a paradoxical embolus if a patent foramen ovale or atrial septal defect is present [83]. There are several cases in the literature in which a devastating paradoxical embolus occurred after a thrombectomy of a dialysis access [84-88]. The most frequent sites of paradoxical embolism are the extremities (50 percent) and the brain (40 percent), while the heart, spleen, and kidney are more rarely affected [89]. (See "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults" and "Embolism to the lower extremities".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pulmonary hypertension in adults".)
SUMMARY AND RECOMMENDATIONS
●Overview – Patients with end-stage kidney disease (ESKD), particularly those on hemodialysis (HD), are at increased risk for development or worsening of pulmonary hypertension (PH). The increased risk is related in part to the arteriovenous (AV) access although other factors related to ESKD also contribute. (See 'Incidence' above and 'Classification and pathogenesis' above.)
●Clinical features – The symptoms and signs of PH in patients with ESKD are the same as in those without ESKD (eg, progressive dyspnea, fatigue, syncope, signs of right heart failure). Similar to PH associated with other etiologies, PH in patients with ESKD is progressive and may only be suspected when PH progresses in severity and right heart failure develops. (See 'Clinical features' above.)
●Diagnosis and evaluation – Evaluation and diagnosis of PH in patients with ESKD are similar to those for patients without ESKD (algorithm 1). We typically begin with transthoracic echocardiography, a search for common etiologies associated with PH, and the selective performance of right heart catheterization (RHC) to confirm or exclude PH. (See 'Initial diagnostic evaluation' above.)
●Management – For patients with ESKD-related PH (ESKD-PH), we follow the same basic principles of management as for other patients with PH (algorithm 2). Patients should be comanaged by clinicians who have expertise in ESKD as well as clinicians with expertise in PH.
•General measures – Patients with ESKD-PH should exercise as tolerated, receive routine vaccinations, be counselled against smoking and vaping, and maintain a normal body mass index. When indicated, they should also be treated with oxygen and diuretics (when feasible). We typically manage volume aggressively. We optimize therapies for any comorbidities known to be associated with or worsen PH, particularly heart failure, obstructive sleep apnea, and underlying lung disease. (See 'General measures in all patients' above.)
•Patients not yet on dialysis – For patients with preexisting, symptomatic PH who are being considered for maintenance dialysis, we suggest peritoneal dialysis (PD) rather than HD as the choice of dialysis modality (Grade 2C). PD obviates the need for AV access placement and provides daily ultrafiltration that may prevent interdialytic volume overload. For most patients who are not suited to, decline, or fail PD, we evaluate for HD using a low-flow AV access (eg, radial-cephalic AV fistula). (See 'Patients on hemodialysis' above and 'Predialysis patients' above.)
•Patients already on dialysis
-Volume management – All patients on HD or PD with ESKD-PH should undergo aggressive removal of volume. We maintain the estimated dry weight as low as possible without causing intra- or interdialytic hypotension. (See 'Volume management' above.)
-AV access management – For patients with ESKD-PH who have an AV access, we assess flow through the AV access (typically using Doppler ultrasonography) and also measure the potential contribution of flow through the AV access to pulmonary hemodynamics. Patients who have severe symptoms of PH generally require ligation of their AV access. For patients with mild-to-moderate symptoms (eg, New York Heart Association class I to II) who have either high-flow AV access (ie, flow ≥1500 mL/min ) or moderate flow (800 to 1500 mL/min) and significant reduction in pulmonary pressures with AV access compression, we suggest a flow reduction procedure (eg, precision banding) rather than observation (Grade 2C). In all others, therapy should be individualized. (See 'AV access management' above.)
•Refractory disease – Patients with persistent, severe PH (eg, severe symptoms and/or mean pulmonary arterial pressure greater than 35 mmHg) despite dialysis and AV fistula management should be referred to centers with expertise in the management of PH for possible evaluation in trials of PH-specific therapy. (See 'Refractory disease' above.)
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