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Perit Dial Int 29(2): 191-198
2009
© 2009 International Society for Peritoneal Dialysis
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Clinical

PULMONARY HYPERTENSION IN PERITONEAL DIALYSIS PATIENTS: PREVALENCE AND RISK FACTORS

Aydin Ünal1, Murat Sipahioglu1, Fatih Oguz2, Mehmet Kaya2, Hamit Kucuk3, Bulent Tokgoz1, Hakan Buyukoglan4, Oktay Oymak1 and Cengiz Utas1

Departments of Nephrology1 Cardiology2 Internal Medicine3 and Chest Diseases4 Erciyes University, Kayseri, Turkey

Correspondence to: A. Ünal, Department of Nephrology, Erciyes University Medical School, Kayseri, 38039 Turkey. aydinunal2003{at}gmail.com


   ABSTRACT
TOP
 ABSTRACT
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 DISCLOSURE
 REFERENCES
 

{diamondsuit} Aim: To investigate the prevalence of pulmonary arterial hypertension (PAH) and the possible contributing factors for PAH in patients receiving regular continuous ambulatory peritoneal dialysis (CAPD).

{diamondsuit} Patients and Methods: The study included 135 CAPD patients and 15 disease-free controls. Patients that had chronic obstructive pulmonary disease, severe mitral or aortic valve disease, connective tissue disease, history of pulmonary embolism, left ventricular ejection fraction <50%, or chest wall or parenchymal lung disease were excluded. All patients and controls were examined using echocardiography and bioelectrical impedance analysis. PAH was defined as systolic pulmonary artery pressure (PAP) >35 mmHg at rest.

{diamondsuit} Results: Mean systolic PAP was higher in the CAPD patients than in the controls (19.66 ± 11.66 vs 14.27 ± 4.55 mmHg, p = 0.001). PAH was detected in 17 (12.6%) of the 135 CAPD patients. Mean systolic PAP was significantly higher in patients with PAH than in those without PAH (42.00 ± 9.13 vs 16.44 ± 7.83 mmHg, p = 0.001). Serum albumin level and ejection fraction were lower in patients with PAH than in those without PAH (p = 0.001 and 0.003 respectively). The ratio of extracellular water/total body water (ECW/TBW), which can reflect hydration status, was significantly higher in patients with PAH than in those without PAH (p = 0.008). In the PD group, no patients were hypovolemic; 51 (37.8%) of the 135 PD patients were hypervolemic and 84 (62.2%) were normovolemic. Only 3 of the 17 patients with PAH were normovolemic; the rest were hypervolemic. Mean systolic PAP was significantly higher in hypervolemic PD patients (24.57 ± 14.19 mmHg) than in normovolemic PD patients (16.68 ± 7.61 mmHg) (p = 0.001). PAP correlated with ECW/TBW (r = 0.317, p = 0.001) and left ventricular mass index (LVMI; r = 0.286, p = 0.001). On the other hand, it inversely correlated with serum albumin level (r = –0.281, p = 0.001), hemoglobin level (r = –0.165, p = 0.044), and ejection fraction (r = –0.263, p = 0.001). Serum albumin level, ECW/TBW, and LVMI were found in multivariate analysis to be independent risk factors for PAP.

{diamondsuit} Conclusion: PAH is a frequent cardiovascular complication in CAPD patients. Serum albumin level, hypervolemia, and LVMI are major risk factors for PAH. Therefore, strategies for treatment of hypervolemia, left ventricular hypertrophy, and hypoalbuminemia should be enhanced to prevent the development of PAH in CAPD patients.

KEY WORDS: Pulmonary arterial hypertension; CAPD; serum albumin level; left ventricular mass index (LVMI); hypervolemia.

It is well known that cardiovascular complications are the major causes of mortality in patients with endstage renal disease (ESRD) (1). Pulmonary arterial hypertension (PAH) is one of these complications. It is a progressive disorder and may lead to right heart failure and even sudden cardiac death (2). It may be primary or secondary to cardiac or lung disease. The prevalence of PAH in patients with ESRD is reported to be between 25% and 60% (3–10). Several causes, such as pathological changes in lung anatomy and function due to uremia itself, the presence of an arteriovenous fistula, vascular calcifications, and endothelial dysfunction, have been suggested causes of development of PAH in patients with ESRD (11). In the literature, to our best knowledge, only one study has investigated PAH in peritoneal dialysis (PD) patients (5). Marangoni et al. reported a correlation between measurements of pulmonary artery pressure (PAP) by Doppler echocardiography and by an invasive method (12). In the present study, we aimed to investigate echocardiographically the prevalence of PAH and possible factors contributing to PAH in PD patients.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 DISCLOSURE
 REFERENCES
 
PATIENTS
This study was performed in 135 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) due to ESRD and in 15 control subjects without disease. The study protocol was approved by the local ethics committee. The study procedures were approved by all patients and controls. Patients with chronic obstructive pulmonary disease (COPD), severe mitral or aortic valve disease, connective tissue disease, left ventricular ejection fraction < 50%, history of pulmonary embolism, or chest wall or parenchymal lung disease were excluded. There was no significant difference between patients and controls with respect to age, gender, smoking, white blood cell count (WBC), triglyceride, low-density lipoprotein (LDL), or total cholesterol levels (p > 0.05).

ECHOCARDIOGRAPHIC EVALUATION
All echocardiographic evaluations were performed by the same cardiologist (FO), using the Vivid 7 Dimension (GE Medical Systems, Horten, Norway) echocardiography machine. Two-dimensional and M-mode Doppler echocardiographic images were obtained from apical or parasternal windows in the left lateral recumbent position for each patient and control. In the presence of tricuspid valve regurgitation, systolic right ventricular (or systolic pulmonary artery) pressure was calculated using the modified Bernoulli equation: PAP = 4 x (tricuspid systolic jet)2 + 10 mmHg (13). PAH is defined as an elevation of mean PAP above 25 mmHg at rest in the setting of normal or reduced cardiac output and normal pulmonary capillary pressure (14). If echocardiographic criteria are used, PAH is defined as systolic PAP > 35 mmHg at rest (14). Therefore, in the present study, PAH was defined as systolic PAP > 35 mmHg at rest. End-diastolic left ventricular septal and posterior wall thickness and internal dimensions were used to calculate left ventricular mass (LVM) using the following equation: LVM = 0.8{1.04[(LVIDD + PWTD + IVSTD)3 – IVSTD3]} + 0.6 g, where LVIDD is left ventricular internal diameter in diastole, PWTD is posterior wall thickness in diastole, and IVSTD is interventricular septum thickness in diastole (15). Left ventricular hypertrophy was defined as left ventricular mass index (LVMI; calculated as LVM in grams divided by body surface area in square meters) higher than 116.0 g/m2 for men and 104.0 g/m2 for women (15). Body surface area was calculated using Mosteller's formula (16).

BLOOD SAMPLES
Blood samples were taken from all patients for laboratory examinations, including complete blood count, serum creatinine, albumin, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), and high-sensitivity C-reactive protein (hs-CRP) levels; plasma asymmetric dimethylarginine (ADMA) level, and total lipid profile on the same day on which echocardiographic evaluation was performed. The iPTH level was measured by radioimmunoassay (Immunotech, Marseille, France). Plasma concentration of ADMA was measured by high performance liquid chromatography (HPLC) with pre-column derivatization. After adding an internal standard, plasma samples were treated with sulfosalicylic acid. The precipitated protein was removed by centrifugation and HPLC was performed on an Agilent 1100 series, binary gradient, automated sample–reagent mixing, and fluorescence detection system (Agilent Technologies, Waldbronn, Germany). Serum hs-CRP was measured by CardioPhase hsCRP on a Dade Behring analyzer (both by Dade Behring, Marburg, Germany).

PERITONEAL EQUILIBRATION TEST (PET)
The PET reported on the day closest to the patient's echocardiographic examination was evaluated for the analysis. All patients had a standard PET as defined by Twardowski (17). According to 4-hour dialysate-to-plasma ratio (D/P) for creatinine as defined by Twardowski (17), patients were categorized as one of the following four peritoneal transport types: high (above +1 SD from the mean), high average (between the mean and +1 SD), low average (between the mean and –1 SD), or low (below –1 SD from the mean).

Drained dialysate and 24-hour urine (if residual renal function was present) were collected within 1 day before the PET. Creatinine (by the Jaffe rate method) and urea nitrogen (by the urease conductivity method) were measured in blood, urine, and drained dialysate. Residual glomerular filtration rate (GFR) was calculated as the mean of urinary creatinine and urea clearances standardized to 1.73 m2 body surface area. Weekly Kt/V urea was calculated as the ratio of urinary + 24-hour dialysate urea clearance to total body water (TBW; in liters); TBW or pool volume was calculated by the method of Watson et al. (18).

Patients with a history of peritonitis within the previous 2 months, dialysate leak, or dialysis catheter dysfunction did not have a PET performed. A PET was also not performed in patients that had their PD catheter inserted within the previous 1 month.

All patients and controls were examined using bioelectrical impedance analysis to estimate the ratio of extracellular water (ECW) to total body water (ECW/TBW). According to the mean ECW/TBW of the control group, the PD patients were categorized as having one of the following three volume statuses: hypervolemic (above +2 SD from the mean), normovolemic (between +2 SD and –2 SD), or hypovolemic (below –2 SD from the mean).

STATISTICAL ANALYSIS
SPSS 11.0 software (SPSSFW; SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. The Kolmogorov–Smirnov test was used to determine normality of distributions of variables. Continuous variables with normal distribution are presented as mean ± SD. Median value is used where normal distribution is absent. Statistical analysis for the parametric variables was performed using the Student's t-test between two groups. The Mann–Whitney U test was used to compare nonparametric variables between two groups. The correlation analysis was evaluated by Pearson's correlation test for parametric variables and by Spearman's correlation test for nonparametric variables. Qualitative variables are given as percent and the correlation between categorical variables was investigated using the chisquare test. Multivariate regression analysis was performed to determine the relationship between PAP and the following variables: residual GFR, ECW/TBW, LVMI, hemoglobin, and serum levels of albumin, iPTH, and hs-CRP. A p value of <0.05 was considered significant.


   RESULTS
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 DISCLOSURE
 REFERENCES
 
Mean age of the 135 patients was 47.68 ± 13.69 years; 64 of the 135 patients were female. Pulmonary arterial hypertension was found in 17 (12.6%) of the 135 CAPD patients. The etiology of ESRD was hypertension in 42 (31.1%), diabetes mellitus in 34 (25.2%), glomerulonephritis in 17 (12.6%), polycystic kidney disease in 4 (3.0%), other causes in 20 (14.8%), and unknown in 18 (13.3%) patients.

Clinical, laboratory, and echocardiographic parameters of the 17 patients with PAH are compared to 118 patients without PAH in Table 1. The number of antihypertensive drugs, ECW/TBW, and PAP were significantly higher in patients with PAH than in those without PAH (p = 0.022, 0.008, and 0.001, respectively). Serum albumin and triglyceride levels and ejection fraction were significantly lower in patients with PAH than in patients without PAH (p = 0.001, 0.001, and 0.003, respectively). When other clinical, laboratory, echocardiographic, demographic, and PET parameters and indexes of PD in CAPD patients with PAH were compared to CAPD patients without PAH, there were no significant differences between the two groups in terms of age, gender, smoking, presence of diabetes or hypertension, use of erythropoietin (EPO), duration of dialysis, systolic and diastolic blood pressure, body mass index; WBC, Hb, serum levels of creatinine, alkaline phosphatase, iPTH, LDL, total cholesterol, glucose, hs-CRP, calcium–phosphate product (CaxP); plasma ADMA level, 4-hour D/P creatinine, peritoneal transport group categorized according to 4-hour D/P creatinine, D/D0 glucose, weekly Kt/V urea, weekly creatinine clearance, residual GFR, amount of ultrafiltration, LVM, LVMI, or presence of left ventricular hypertrophy (p > 0.05).


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  		TABLE 1 Clinical, Laboratory, and Echocardiographic Parameters in Patients With and Patients Without Pulmonary Arterial Hypertension (PAH) on CAPD

 

Pulmonary artery pressure correlated with ECW/TBW (r = 0.317, p = 0.001), LVM (r = 0.253, p = 0.002), and LVMI (r = 0.286, p = 0.001). It inversely correlated with serum albumin level (r = –0.281, p = 0.001), serum triglyceride level (r = –0.172, p = 0. 036), Hb level (r = –0.165, p = 0.044), and ejection fraction (r = –0.263, p = 0. 001). However, it did not correlate with age, body mass index, residual GFR, weekly Kt/V urea, weekly creatinine clearance, duration of dialysis, amount of ultrafiltration; WBC, serum levels of alkaline phosphatase, iPTH, hs-CRP, creatinine, glucose, total cholesterol, LDL, CaxP levels; plasma ADMA level, 4-hour D/P creatinine, D/D0 glucose, or systolic and diastolic blood pressures (p > 0.05).

Amount of ultrafiltration inversely correlated with 4-hour D/P creatinine (r = –0.287, p = 0.001). Serum albumin level inversely correlated with LVMI (r = –0.211, p = 0.010) and ECW/TBW (r = –0.285, p = 0.001). Serum albumin level was significantly lower in high transporters than in low transporters (2.83 ± 0.56 vs 3.36 ± 0.11 mg/dL, p = 0.007).

Table 2 demonstrates the associations between clinical, laboratory, and echocardiographic parameters and index of PD adequacy and PAP in multivariate regression analysis. In multivariate analysis, serum albumin level, ECW/TBW, and LVMI were found to be independent risk factors for PAP.


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  		TABLE 2 Associations Between Clinical, Laboratory, and Echocardiographic Parameters and Index of Peritoneal Dialysis Adequacy and Pulmonary Artery Pressure (by Multivariate Regression Analysis)a

 

In the control group, mean ECW/TBW was 0.34 ± 0.04. According to the mean ECW/TBW of the control group, the PD patients were categorized as one of the following three volume statuses: hypervolemic (ECW/TBW > 0.42), normovolemic (ECW/TBW 0.26 – 0.42), or hypovolemic (ECW/TBW < 0.26). In the PD group, no patients were hypovolemic; 51 (37.8%) of the 135 PD patients were hypervolemic and 84 (62.2%) were normovolemic.

Table 3 shows clinical, laboratory, and echocardiographic parameters of the hypervolemic and normovolemic CAPD patients. Mean systolic PAP and ECW/TBW were significantly higher in hypervolemic PD patients than in normovolemic PD patients (p = 0.001 for both). Similarly, presence of PAH was significantly more frequent in hypervolemic PD patients than in normovolemic PD patients (p = 0.001). Hemoglobin value was significantly lower in hypervolemic PD patients than in normovolemic PD patients (p = 0.019). On the other hand, there were significant differences between the groups in terms of systolic and diastolic blood pressure values, serum albumin level, ejection fraction, LVMI, and presence of left ventricular hypertrophy (p > 0.05).


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  		TABLE 3 Clinical, Laboratory, and Echocardiographic Parameters in Hypervolemic and Normovolemic Patients on CAPD

 

The high PAP group (i.e., patients with PAH) was stratified as normovolemic and hypervolemic: only 3 patients were normovolemic; most (14 of 17 patients) of the patients with PAH were hypervolemic.


   DISCUSSION
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
DISCLOSURE
 REFERENCES
 
Pulmonary arterial hypertension is a disease characterized by elevated artery pressure and vascular resistance in the pulmonary vessels (14). For development of PAH, two main mechanisms are required: elevated pulmonary vascular resistance and elevated pulmonary blood flow (6). Increased pulmonary vascular resistance is associated with three major factors: vasoconstriction, thrombosis, and pulmonary vascular remodeling, which is the most important factor and characterizes the presence of smooth muscle cells within the small arteries of the respiratory acini (19). In pulmonary hypertension developing in patients with ESRD, two special conditions are present. The first condition is uremia itself. Yigla et al. reported that mean systolic PAP significantly decreased after successful renal transplantation (from 47 ± 11 to 32 ± 8 mmHg) in 5 hemodialysis (HD) patients with PAH, while their arteriovenous access was intact (7). The second condition is specific to patients undergoing HD via an arteriovenous access. Yigla et al. also reported that compression of an arteriovenous access by a sphygmomanometer decreased both mean cardiac output and systolic PAP in 4 HD patients (7).

In patients with ESRD, hypervolemia, anemia, and increased cardiac output, which is increased by arteriovenous access, are factors contributing to the elevation of pulmonary blood flow rate, which may lead to pulmonary hypertension. In our study, when patients were classified according to volume status, PAP was significantly higher in the hypervolemic PD group than in the normovolemic PD group. Most pulmonary hypertensive patients were hypervolemic. Furthermore, ECW/TBW was meaningfully higher in patients with PAH than in those without PAH. Also, ECW/TBW was an independent risk factor in multivariate analysis, and PAP correlated with this ratio. These findings demonstrate that hypervolemia is a very important determining factor for the development of PAH in PD patients. However, to definitively determine the relationship between hypervolemia and pulmonary hypertension in PD patients, systolic PAP was re-evaluated after the patients achieved normovolemia.

Unfortunately, our study was cross-sectional. This relationship may be better understood when a prospective study is completed.

To our best knowledge, only a few studies have investigated the prevalence and developmental mechanisms of PAH in patients receiving regular HD up to now. The prevalence of PAH was very high in these studies. Acarturk and co-workers reported that the prevalence of PAH (defined as PAP ≥ 25 mmHg) was 43.7% in 32 patients (6). Yigla et al. found that the prevalence of PAH (defined as PAP > 35 mmHg) was 39.7% in 58 patients (7). The prevalence of PAH (defined as PAP > 35 mmHg) was shown to be 26.7% in another study (3). In a study performed by Amin et al., PAH (defined as PAP > 35 mmHg) was detected in 15 (29%) of 51 HD patients (10). However, in our study, we detected PAH in 17 (12.6%) of the 135 patients undergoing PD. The prevalence of PAH was lower in our study than in the above-mentioned studies.

In the literature there are only two studies of PD patients that include data about PAH (5,7). In the study by Yigla et al., pulmonary hypertension was investigated in patients on HD. That study included 58 HD patients. The 5 patients treated with PD were selected as the control group. None of these 5 PD patients had PAP > 35 mmHg (7). In other words, in that study, pulmonary hypertension was actually evaluated only in HD patients, not in PD patients. In another study, Kumbar and co-workers retrospectively found that the prevalence of PAH was 42% in 36 PD patients (5). That result was much higher than in our study. The difference between our findings and theirs appears to result from patient choice. In their study, patients with congestive heart failure — which can lead to pulmonary venous hypertension and consequently to pulmonary hypertension, and is one of the most common causes of pulmonary hypertension (14) — were not excluded and the mean ejection fraction of the patients with PAH was 46.3%. On the other hand, in our study and most of the above-mentioned studies that were performed in HD patients, patients with an ejection fraction below 50% were excluded.

Peritoneal membrane transport characteristics are the determining factors in fluid and solute exchange between the peritoneal cavity and blood circulation in PD patients. Serum albumin level is lower in high transporters than in low transporters (20). Hypoalbuminemia in high transporters may result from increased dialytic albumin loss, insufficient nutrition, and relative hemodilution due to insufficient ultrafiltration caused by increased dialysate glucose absorption (21). Furthermore, it is well documented that the prognosis is poor in high transporters on PD. Similarly, in the present study, serum albumin level was significantly lower in high transporters than in low transporters but there was no significant difference between patients with and patients without PAH in terms of peritoneal transport characteristics. Serum albumin is one of the major prognostic indicators in PD patients. Reduced serum albumin level is related to increased mortality and morbidity in PD (22,23). Therefore, it not a surprising finding that serum albumin level was lower in patients with PAH than in patients without PAH in our study, that it inversely correlated with PAP, and that it was an independent risk factor in multivariate analysis. The relationship between serum albumin level and PAP is probably a consequence of decreased fluid removal and hypervolemia. The inverse correlation between serum albumin level and ECW/TBW also supports our opinion.

Cardiovascular complications are major causes of morbidity and mortality in ESRD patients. Left ventricular mass index is one of the most important prognostic factors for cardiovascular events (24). Although there was no statistically significant difference between patients with and patients without PAH with respect to mean LVM and LVMI values and presence of left ventricular hypertrophy, these values were higher in patients with PAH than in those without PAH. In addition, PAP positively correlated with LVM and LVMI. Also, LVMI was an independent risk factor for PAP in multivariate analysis. Similarly, Tarrass et al. found that, although the mean LVMI value was higher in HD patients with PAH than in those without PAH, there was no significant difference between the groups (3). Although there was a significant difference between the groups in our study, left ventricular hypertrophy was more frequent in the hypervolemic PD patients than in the normovolemic PD patients. Ejection fraction was lower in patients with PAH than in those without PAH; PAP correlated with ejection fraction. All findings about LVMI, left ventricular hypertrophy, and ejection fraction showed that PAP is also related to changes in intravascular volume (as are LVMI and ejection fraction), and that volume expansion may lead to increased atrial pressure and thus to pulmonary hypertension.

Pulmonary artery pressure also relates to changes in dialysis adequacy. Hypervolemia may develop if PD is inadequate. Such volume expansion may lead to increased atrial pressure and thus to pulmonary hypertension. However, PAP did not correlate with the criteria of dialysis adequacy, including residual GFR, weekly Kt/V urea, weekly creatinine clearance, duration of dialysis, amount of ultrafiltration, 4-hour D/P creatinine, and D/D0 glucose, in our study.

Vascular calcifications in patients with ESRD are very common and have been defined as risk factors for cardiovascular mortality in the general population. One of several explanations for the pathogenesis of vascular calcification is dysregulation of calcium/phosphate metabolism in ESRD (25). Metastatic calcifications can develop in any tissue; however, they commonly occur in the lung, kidney, and stomach. The calcifications generally deposit in the interstitium of the alveolar septum and the walls of the pulmonary vessels in the lungs and may adversely affect pulmonary function (26,27). In a study performed by Akmal et al. in dogs, it was found that PAP was significantly higher in non-parathyroidectomized animals with chronic renal failure than in normal animals and in parathyroidectomized animals with chronic renal failure; they suggested that an elevated PTH level induces PAH (27). Kumbar et al. reported that PTH levels significantly correlate to PAP values in patients treated with PD (5). However, Yigla et al. found that there was no significant correlation between pulmonary calcifications — shown by uptake of technetium-99m methylene diphosphonate — and PAH in HD patients (9). Similarly, in 51 patients undergoing HD, Amin et al. found that there was no significant difference between patients with PAH and those without PAH in terms of PTH and pulmonary calcification (10). In our study, there was no meaningful difference between PD patients with and PD patients without PAH with respect to CaxP, alkaline phosphatase, and iPTH levels. Also, PAP did not correlate with iPTH level or CaxP. In addition, in multivariate analysis, iPTH was not an independent risk factor for PAP.

In HD patients, the arteriovenous fistula-induced increased cardiac output contributes to the development of PAH (28). Anemia is one of the most common complications of chronic renal disease and it can also contribute to the development of PAH by increasing cardiac output in patients with ESRD. Similarly, in our study, PAP values inversely correlated with Hb levels; however, there was no difference between patients with and patients without PAH in terms of Hb. Also, in multivariate analysis, Hb was not found to be an independent risk factor for PAP.

The results of these studies that investigated effects of EPO in the development of PAH are controversial. In some studies, it was found that EPO might play a protective role in the development of PAH (29,30); whereas, in other studies, it was determined that EPO had pulmonary hypertensive effects (31–33). In the present work, we found no significant difference in EPO use between patients with and patients without PAH.

Endothelium-derived nitric oxide (NO) is a potent endogenous vasodilator (34) and also suppresses vascular smooth muscle proliferation (35). ADMA is an endogenous and competitive inhibitor of NO synthase and a risk factor for endothelial dysfunction (36,37). In a study performed by Böger et al., elevated ADMA was associated with impaired endothelium-dependent vasodilatation and reduced urinary nitrate excretion. This abnormality was reversed by administration of L-arginine (36). As mentioned above, vasoconstriction is one of the major factors in increased pulmonary vascular resistance. It appears to result from an abnormality in potassium channels of arterial smooth muscle and endothelial dysfunction associated with increased vasoconstrictors, such as endothelin-1, and decreased vasodilators, such as NO (19). Plasma ADMA levels are elevated in patients with chronic renal failure (38). ADMA is also an independent predictor of cardiovascular events in HD patients (39). In addition, ADMA is strongly associated with basal NO release in resistance arteries of patients undergoing PD (40). In a study performed in 42 HD patients, Nakhoul et al. found that plasma endothelin-1 levels were higher in HD patients, with or without PAH, than in controls. They also found that plasma NO metabolites in HD patients with PAH were significantly higher compared with HD patients without PAH and were similar to those in controls. They suggested that this endothelial dysfunction contributes to the development of PAH (8). However, in the present study, plasma ADMA levels in PD patients with PAH were similar to those in PD patients without PAH and PAP values did not correlate with plasma ADMA levels. In addition, in multivariate analysis, plasma ADMA level was not an independent risk factor for PAP.

Systemic inflammation may also play a major role in PAH in COPD patients. To the best of our knowledge, there is no study that investigates the relationship between systemic inflammation parameters, such as CRP, and PAH in dialysis patients (HD or PD). In a study performed by Joppa and colleagues, it was found that COPD patients with PAH had higher levels of circulating CRP and tumor necrosis factor-alpha than COPD patients without PAH. Also, there was a significant relationship between serum CRP levels and systolic PAP (41). However, we detected no significant difference between patients with and patients without PAH with respect to the systemic inflammation markers hs-CRP and WBC.

In conclusion, the prevalence of PAH was lower in PD patients than in HD patients in our study. Therefore, when patients that have increased risk for the development of PAH — such as severe mitral or aortic valve disease — are to undergo dialysis, starting with PD may be a reasonable option to prevent PAH. Hypervolemia was a very important determining factor for the development of PAH in our PD patients. However, to definitively determine the relationship between hypervolemia and pulmonary hypertension in PD patients, once the patients have achieved normovolemia, systolic PAP should be reevaluated. This relationship may be better elucidated (teased out) in a future prospective study. In addition, because decreased serum albumin level and LVMI were independent risk factors for PAP in our study, strategies for treatment of hypervolemia, left ventricular hypertrophy, and hypoalbuminemia should be enhanced to prevent the development of PAH in PD patients.


   DISCLOSURE
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 DISCLOSURE
REFERENCES
 
This work was supported in part (for ADMA measurements) by Turkish Society of Nephrology. No conflict of interest.

Received 20 March 2008; accepted 4 July 2008.


   REFERENCES
TOP
 ABSTRACT
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 DISCLOSURE
 REFERENCES
 

  1. Bloembergen WE. Cardiac disease in chronic uremia: epidemiology. Adv Ren Replace Ther 1997;4 : 185-93.[Medline]
  2. Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997; 336:111 -17.[Free Full Text]
  3. Tarrass F, Benjelloun M, Medkouri G, Hachim K, Benghanem MG, Ramdani B. Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis. Hemodial Int2006; 10:356 -9.[Medline]
  4. Harp RJ, Stavropoulos SW, Wasserstein AG, Clark TW. Pulmonary hypertension among end-stage renal failure patients following hemodialysis access thrombectomy. Cardiovasc Intervent Radiol2005; 28:17 -22.[Medline]
  5. Kumbar L, Fein PA, Rafiq MA, Borawski C, Chattopadhyay J, Avram MM. Pulmonary hypertension in peritoneal dialysis patients. Adv Perit Dial 2007; 23:127 -31.[Medline]
  6. Acarturk G, Albayrak R, Melek M, Yuksel S, Uslan I, Atli H, et al. The relationship between arteriovenous fistula blood flow rate and pulmonary artery pressure in hemodialysis patients. Int Urol Nephrol 2008; 40:509 -13.[Medline]
  7. Yigla M, Nakhoul F, Sabag A, Tov N, Gorevich B, Abassi Z, et al. Pulmonary hypertension in patients with end-stage renal disease. Chest 2003; 123:1577 -82.[Abstract/Free Full Text]
  8. Nakhoul F, Yigla M, Gilman R, Reisner SA, Abassi Z. The pathogenesis of pulmonary hypertension in haemodialysis patients via arterio-venous access. Nephrol Dial Transplant2005; 20:1686 -92.[Abstract/Free Full Text]
  9. Yigla M, Keidar Z, Safadi I, Tov N, Reisner SA, Nakhoul F. Pulmonary calcification in hemodialysis patients: correlation with pulmonary artery pressure values. Kidney Int 2004;66 : 806-10.[Medline]
  10. Amin M, Fawzy A, Hamid MA, Elhendy A. Pulmonary hypertension in patients with chronic renal failure: role of parathyroid hormone and pulmonary artery calcifications. Chest 2003;124 : 2093-7.[Abstract/Free Full Text]
  11. Buemi M, Senatore M, Gallo GC, Crascì E, Campo S, Sturiale A, et al. Pulmonary hypertension and erythropoietin. Kidney Blood Press Res 2007;30 : 248-52.[Medline]
  12. Marangoni S, Quadri A, Dotti A, Scalvini S, Volterrani M, Schena M, et al. Noninvasive assessment of pulmonary hypertension: a simultaneous echo-Doppler hemodynamic study. Cardiology 1988;75 : 401-8.[Medline]
  13. Dabestani A, Mahan G, Gardin JM, Takenaka K, Burn C, Allfie A, et al. Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography. Am J Cardiol1987; 59:662 -8.[Medline]
  14. Rosenkranz S. Pulmonary hypertension: current diagnosis and treatment. Clin Res Cardiol 2007;96 : 527-41.[Medline]
  15. Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, et al. Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA2004; 292:2350 -6.[Abstract/Free Full Text]
  16. Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987;317 : 1098.[Medline]
  17. Twardowski ZJ. Clinical value of standardized equilibration tests in CAPD patients. Blood Purif 1989;7 : 95-108.[Medline]
  18. Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr 1980;33 : 27-39.[Abstract/Free Full Text]
  19. Minai OA, Budev MM. Diagnostic strategies for suspected pulmonary arterial hypertension: a primer for the internist. Cleve Clin J Med 2007; 74:737 -47.[Abstract/Free Full Text]
  20. Cueto-Manzano AM, Espinosa A, Hernández A, Correa-Rotter R. Peritoneal transport kinetics correlate with serum albumin but not with the overall nutritional status in CAPD patients. Am J Kidney Dis 1997; 30:229 -36.[Medline]
  21. Blake PG. What is the problem with high transporters? Perit Dial Int 1997;17 : 317-20.[Free Full Text]
  22. Gamba G, Mejía JL, Saldívar S, Peña JC, Correa-Rotter R. Death risk in CAPD patients. The predictive value of the initial clinical and laboratory variables. Nephron1993; 65:23 -7.[Medline]
  23. Blake PG, Flowerdew G, Blake RM, Oreopoulos DG. Serum albumin in patients on continuous ambulatory peritoneal dialysis—predictors and correlations with outcomes. J Am Soc Nephrol1993; 3:1501 -7.[Abstract]
  24. Kessler M, Zannad F, Lehert P, Grünfeld JP, Thuilliez C, Leizorovicz A, et al.; for the FOSIDIAL Investigators. Predictors of cardiovascular events in patients with end-stage renal disease: an analysis from the Fosinopril in Dialysis Study. Nephrol Dial Transplant 2007; 22:3573 -9.[Abstract/Free Full Text]
  25. Davies MR, Hruska KA. Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int2001; 60:472 -9.[Medline]
  26. Bendayan D, Barziv Y, Kramer MR. Pulmonary calcifications: a review. Respir Med 2000;94 : 190-3.[Medline]
  27. Akmal M, Barndt RR, Ansari AN, Mohler JG, Massry SG. Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Kidney Int 1995;47 : 158-63.[Medline]
  28. Abassi Z, Nakhoul F, Khankin E, Reisner SA, Yigla M. Pulmonary hypertension in chronic dialysis patients with arteriovenous fistula: pathogenesis and therapeutic prospective. Curr Opin Nephrol Hypertens 2006; 15:353 -60.[Medline]
  29. Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, et al. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation 2006;113 : 1442-50.[Abstract/Free Full Text]
  30. Petit RD, Warburton RR, Ou LC, Brinck-Johnson T, Hill NS. Exogenous erythropoietin fails to augment hypoxic pulmonary hypertension in rats. Respir Physiol 1993;91 : 271-82.[Medline]
  31. Hasegawa J, Wagner KF, Karp D, Li D, Shibata J, Heringlake M, et al. Altered pulmonary vascular reactivity in mice with excessive erythrocytosis. Am J Respir Crit Care Med2004; 169:829 -35.[Abstract/Free Full Text]
  32. Briest W, Homagk L, Baba HA, Deten A, Rassler B, Tannapfel A, et al. Cardiac remodeling in erythropoietin-transgenic mice. Cell Physiol Biochem 2004;14 : 277-84.[Medline]
  33. Allegra A, Giacobbe MS, Corvaia E, Cinquegrani M, Corvaja E, Giorgianni G, et al. Possible role of erythropoietin in the pathogenesis of chronic cor pulmonale. Nephrol Dial Transplant 2005; 20:2866 -7.[Free Full Text]
  34. Palmer RM, Ferrige AG, Moncada S. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327:524 -6.[Medline]
  35. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989; 83:1774 -7.[Medline]
  36. Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998;98 : 1842-7.[Abstract/Free Full Text]
  37. Vallance P, Leone A, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol 1992;20 (Suppl 12):S60 -2.[Medline]
  38. Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339:572 -5.[Medline]
  39. Zoccali C, Bode-Böger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with endstage renal disease. A prospective study. Lancet 2001;358 : 2113-17.[Medline]
  40. Mittermayer F, Schaller G, Pleiner J, Vychytil A, Sunder-Plassmann G, Hörl WH, et al. Asymmetrical dimethyl-arginine plasma concentrations are related to basal nitric oxide release but not endothelium-dependent vasodilation of resistance arteries in peritoneal dialysis patients. J Am Soc Nephrol 2005;16 : 1832-8.[Abstract/Free Full Text]
  41. Joppa P, Petrasova D, Stancak B, Tkacova R. Systemic inflammation in patients with COPD and pulmonary hypertension. Chest 2006; 130:326 -33.[Abstract/Free Full Text]



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A. Domenici, R. Luciani, and F. Principe
Pulmonary Hypertension in Dialysis Patients
Perit. Dial. Int., March 1, 2010; 30(2): 251 - 252.
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