Abstract

Introduction

End-stage renal disease (ESRD) affects 10-16% of adults worldwide. It is characterized by a significantly reduced estimated glomerular filtration rate and increased urinary albumin excretion (¹1. Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 2012; 380: 1662-1673, doi: 10.1016/S0140-6736(12)61350-6.
https://doi.org/10.1016/S0140-6736(12)61... ). ESRD is clinically defined as kidney failure requiring dialysis or transplantation, and is associated with high healthcare costs and mortality. ESRD costs nearly US$23 billion each year in health care costs in the US, and the mortality rates are eight times higher in 20- to 64-year-old ESRD patients treated by dialysis than those individuals of similar age (²2. Villar E, McDonald SP, Couchoud C. Incidence of treatment for end-stage renal disease among individuals with diabetes in the U.S. continues to decline: response to Burrows, Li, and Geiss. Diabetes Care 2010; 33: e69, doi: 10.2337/dc10-0074.
https://doi.org/10.2337/dc10-0074... ). The United States Renal Data System annual data report showed that the mortality of chronic kidney disease (CKD) patients in 2008 was 1.7 times higher than that of non-CKD patients after adjusting for age, gender, race, prior hospitalizations, and comorbidity (³3. An X, Mao HP, Wei X, Chen JH, Yang X, Li ZB, et al. Elevated neutrophil to lymphocyte ratio predicts overall and cardiovascular mortality in maintenance peritoneal dialysis patients. Int Urol Nephrol 2012; 44: 1521-1528, doi: 10.1007/s11255-012-0130-3.
https://doi.org/10.1007/s11255-012-0130-... ). In-center hemodialysis and home peritoneal dialysis (PD) are the two most common dialysis therapies. Costs associated with PD are almost US$20,000 lower than those of hemodialysis, but PD and hemodialysis have similar health outcomes (⁴4. Mehrotra R, Chiu YW, Kalantar-Zadeh K, Bargman J, Vonesh E. Similar outcomes with hemodialysis and peritoneal dialysis in patients with end-stage renal disease. Arch Intern Med 2011; 171: 110-118, doi: 10.1001/archinternmed.2010.352.
https://doi.org/10.1001/archinternmed.20... ). Maintenance peritoneal dialysis (MPD) is a common renal replacement therapy for ESRD patients (³3. An X, Mao HP, Wei X, Chen JH, Yang X, Li ZB, et al. Elevated neutrophil to lymphocyte ratio predicts overall and cardiovascular mortality in maintenance peritoneal dialysis patients. Int Urol Nephrol 2012; 44: 1521-1528, doi: 10.1007/s11255-012-0130-3.
https://doi.org/10.1007/s11255-012-0130-... ). However, MPD is complicated by diseases such as pulmonary hypertension (PH).

PH was previously classified into two categories, primary PH or secondary PH, based on the presence of identified causes or risk factors (⁵5. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62: D34-D41, doi: 10.1016/j.jacc.2013.10.029.
https://doi.org/10.1016/j.jacc.2013.10.0... ). PH is linked to diverse etiologies, such as left heart failure, chronic hypoxic lung diseases, collagen vascular disease, portal hypertension, chronic recurrent thromboembolism, human immunodeficiency virus infection, and exposure to drugs and toxins (⁶6. Lundgren J, Radegran G. Pathophysiology and potential treatments of pulmonary hypertension due to systolic left heart failure. Acta Physiol 2014; 211: 314-333, doi: 10.1111/apha.12295.
https://doi.org/10.1111/apha.12295... ⁷7. Seeger W, Adir Y, Barbera JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013; 62: D109-D116, doi: 10.1016/j.jacc.2013.10.036.
https://doi.org/10.1016/j.jacc.2013.10.0... ⁸8. Dai HL, Zhang M, Xiao ZC, Guang XF, Yin XL. Pulmonary arterial hypertension in HIV infection: a concise review. Heart Lung Circ 2014; 23: 299-302, doi: 10.1016/j.hlc.2013.10.088.
https://doi.org/10.1016/j.hlc.2013.10.08... ). PH is frequently associated with CKD and ESRD, and is hemodynamically defined as a mean pulmonary artery pressure (PAP) greater than 25 mmHg. A recent study suggested that left heart dysfunction is the underlying cause of PH in patients with kidney disease (⁹9. Sise ME, Courtwright AM, Channick RN. Pulmonary hypertension in patients with chronic and end-stage kidney disease. Kidney Int 2013; 84: 682-692, doi: 10.1038/ki.2013.186.
https://doi.org/10.1038/ki.2013.186... ). The incidence of PH is high in ESRD patients and ranges from 9 to 39% in Stage 5 CKD patients, between 18.8 and 68.8% in hemodialysis patients, and between 0 and 42% in patients receiving PD treatment (¹⁰10. Nasri H. Unexplained pulmonary hypertension in peritoneal dialysis and hemodialysis patients. Rev Port Pneumol 2013; 19: 238-239, doi: 10.1016/j.rppneu.2013.05.004.
https://doi.org/10.1016/j.rppneu.2013.05... ). Several mechanisms have been proposed for the incidence of PH in kidney diseases, such as left ventricular disorders, arteriovenous fistula, volume overload, sleep disorder, dialysis membrane exposure, endothelial dysfunction, and vascular calcification (¹¹11. Li Z, Liang X, Liu S, Ye Z, Chen Y, Wang W, et al. Pulmonary hypertension: epidemiology in different CKD stages and its association with cardiovascular morbidity. PLoS One 2014; 9: e114392, doi: 10.1371/journal.pone.0114392.
https://doi.org/10.1371/journal.pone.011... ). Genctoy et al. found that older age, lower ejection fraction, and secondary hyperparathyroidism may contribute to PH in CKD with proteinuria (¹²12. Genctoy G, Arikan S, Gedik O. Secondary hyperparathyroidism is associated with pulmonary hypertension in older patients with chronic kidney disease and proteinuria. Int Urol Nephrol 2015; 47: 353-358, doi: 10.1007/s11255-014-0889-5.
https://doi.org/10.1007/s11255-014-0889-... ). Alhamad et al. studied the clinical characteristics of PH patients receiving hemodialysis or peritoneal dialysis versus patients receiving renal transplantation (¹³13. Alhamad EH, Al-Ghonaim M, Alfaleh HF, Cal JP, Said N. Pulmonary hypertension in end-stage renal disease and post renal transplantation patients. J Thorac Dis 2014; 6: 606-616, doi: 10.3978/j.issn.2072-1439.2014.04.29
https://doi.org/10.3978/j.issn.2072-1439... ). However, few studies have investigated the incidence of PH in patients receiving MPD and the risk factors promoting PH in MPD patients.

In this study, we investigated the incidence of PH in patients receiving MPD. We also examined potential risk factors through a detailed analysis of clinical data, laboratory indices, and echocardiographic data that were collected during bi-monthly follow-up visits.

Material and Methods

Patients

Between January 2009 and June 2014, 180 ESRD patients receiving MPD treatment at the Dialysis Center of the Second Affiliated Hospital of Soochow University were selected for this study, which was approved by the Hospital’s Ethical Committee. The patient group consisted of 124 men and 56 women (mean age: 56.43±8.36; mean dialysis time: 36.35±3.38 months). Inclusion criteria for patients in this study were as follows: i ) patients were treated by continuous ambulatory peritoneal dialysis and their daily cumulative dialysate dose was 6-8 L; ii ) patients received renal replacement therapy for longer than 6 months and were in a stable condition; iii ) patients were compliant and willing to be followed up; and iv ) patients were older than 18 years of age. All of the patients received pulmonary perfusion imaging and showed even perfusion without perfusion defects. Written informed consent was obtained from all patients.

The exclusion criteria of patients were as follows: i ) patients with chronic lung disease that could greatly affect PAP (¹⁴14. Zhang R, Tan X, He Q, Chen Q, Gai J, Wei J, et al. Comparison of symptom and risk assessment methods among patients with chronic obstructive pulmonary disease. Chin Med J 2014; 127: 2594-2598.) (e.g., dyspnea and a state of air intake with arterial blood gas analysis showing a pH <7.35, chronic thromboembolic disease, which can also greatly affect PAP (¹⁵15. Taboada D, Pepke-Zaba J, Jenkins DP, Berman M, Treacy CM, Cannon JE, et al. Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease. Eur Respir J 2014; 44: 1635-1645, doi: 10.1183/09031936.00050114.
https://doi.org/10.1183/09031936.0005011... ), obvious arteriovenous ischemia, or thromboembolism diagnosed by imaging methodology); ii ) patients having received renal replacement therapy within the past 6 months or who were hospitalized during renal replacement therapy within the past 3 months; iii ) patients with severe left heart disease, such as New York Heart Association class III/IV heart failure and a left ventricular ejection fraction <50%; and iv ) patients having received prior hemodialysis. Additionally, we excluded patients with the following diseases that cause pulmonary hypertension: congenital heart disease, acute coronary syndrome, postinfarction syndrome, valvular heart disease (valvular regurgitation or grade II or above valvular stenosis), pericardial disease, autoimmune disease, chest wall or lung parenchymal disease, and pulmonary embolism.

Collection of clinical data, laboratory indices, and echocardiographic data

Clinical data including age, gender, smoking (ex-smokers or current smokers), height, weight, interdialytic weight gain, total dialysate, average ultrafiltration volume, liquid removal volume, pulmonary function tests (forced vital capacity and forced expiratory volume in 1 second), dialysis time, systolic pressure, diastolic pressure, mean arterial pressure, and body mass index were recorded. Chronic renal failure and its complications were also recorded. Laboratory indices were recorded, including the serum levels of albumin, total bilirubin, alanine transaminase, aspartate aminotransferase, hemoglobin, brain natriuretic peptide (BNP), parathyroid hormone, calcium, phosphorus, creatinine, urea nitrogen, and C-reactive protein (CRP). Ultrasonic cardiographic data were recorded, including the right ventricular diameter, right ventricular outflow tract diameter, main pulmonary artery diameter, left atrial diameter, left ventricular diastolic diameter, left ventricular systolic diameter, left ventricular outflow tract diameter, interventricular septal thickness, aortic root dimension, ejection fraction, mitral regurgitation, pericardial effusion, and left ventricular mass index.

Follow-up and diagnostic criteria of PH

After collecting clinical data, laboratory indices and data from ultrasonic cardiograms were collected. Patients were followed up bi-monthly. The termination of follow-up included patients with complicated PH or a follow-up time of longer than 36 months. During follow-up, PAP was evaluated by echocardiography. Systolic tricuspid regurgitant jet velocity (V) was measured directly, and PAP was calculated according to Bernoulli’s equation: PAP = 4 × V² + 10 mmHg (¹⁶16. Tokushima T, Utsunomiya T, Yoshida K, Ogawa T, Kido K, Ohtsubo Y, et al. Estimation of the systolic pulmonary arterial pressure using contrast-enhanced continuous-wave Doppler in patients with trivial tricuspid regurgitation. Jpn Heart J 1999; 40: 311-320, doi: 10.1536/jhj.40.311.
https://doi.org/10.1536/jhj.40.311... ,¹⁷17. Ishii M, Kato H, Inoue O, Takagi J, Akagi T, Miyake T, et al. Noninvasive evaluation of systolic pressures of pulmonary artery and right ventricle using contrast-enhanced doppler echocardiography: comparative study using sonicated albumin or glucose solution. Pediatr Cardiol 1996; 17: 175-180, doi: 10.1007/BF02505208.
https://doi.org/10.1007/BF02505208... ). PH was confirmed by a systolic PAP ≥35 mmHg according to echocardiographic assessment of the right heart guidelines published by the American Society of Echocardiography in 2010 (¹⁸18. Mansour IN, Lang RM, Aburuwaida WM, Bhave NM, Ward RP. Evaluation of the clinical application of the ACCF/ASE appropriateness criteria for stress echocardiography. J Am Soc Echocardiogr 2010; 23: 1199-1204, doi: 10.1016/j.echo.2010.07.008.
https://doi.org/10.1016/j.echo.2010.07.0... ). The date and time of diagnosis of PH were recorded, and patients were then categorized into either the PH group or the non-PH group. The clinical differences between PH and non-PH groups were compared to identify risk factors for PH in patients receiving MPD.

Statistical analysis

Data were analyzed by SPSS 20.0 (IBM Corp., USA). Measurement data are reported as means±SD and the differences were measured by the t -test. Enumeration data are reported as percentage or rate, and the differences were compared with the χ² test. Factors related to PH were analyzed by logistic regression analysis. A P value <0.05 was considered to be significant.

Results

Patients receiving MPD diagnosed with PH

After examination of the 180 patients by echocardiography, 60 were diagnosed with PH and categorized into the PH group, with PAP ranging from 35.0 to 62.2 mmHg (mean PAP: 53.6±9.6 mmHg). Therefore, the incidence of PH in this cohort was 33.3%. In the PH group, 40 patients were men, 20 were women, and the mean age was 59.65±11.24 years. The remaining 120 patients were categorized as non-PH and included 84 men and 36 women, with a mean age of 61.15±10.61 years. PAP of the non-PH patients ranged from 12.5 to 34.8 mmHg (mean PAP: 21.3±6.4 mmHg).

Clinical data

Smoking, systolic pressure, diastolic pressure, mean arterial pressure, and the proportion of internal arteriovenous fistula were significantly higher in the PH group than in the non-PH group (all P< 0.05). However, there were no significant differences in age, gender, body mass index, interdialytic weight gain, dialysis time, total dialysate, average ultrafiltration volume, liquid removal volume, forced vital capacity, and forced expiratory volume in 1 second between the PH and the non-PH groups (all P>0.05; Table 1).

Laboratory indices

Serum BNP, phosphorus, and CRP levels were significantly higher in the PH group than in the non-PH group (all P< 0.05). However, serum albumin levels and hemoglobin were significantly lower in the PH group than in the non-PH group (P< 0.05). There were no significant differences in serum total bilirubin, aspartate aminotransferase, alanine transaminase, parathyroid hormone, calcium, creatinine, and urea nitrogen levels between the two groups (P>0.05; Table 2).

Primary disease

With regard to primary diseases in the 180 patients receiving MPD, 35% had chronic glomerulonephritis, 33.3% had hypertensive nephropathy, 18.9% had diabetic nephropathy, and 12.8% had other diseases, such as aristolochic acid nephropathy or polycystic kidney disease The incidence of PH was significantly higher in hypertensive nephropathy patients than in any of the non-hypertensive nephropathy patients (P<0.05). There was no significant difference in the incidence of PH between chronic glomerulonephritis patients, diabetic nephropathy patients, or other primary disease patients (P>0.05; Table 3), indicating that these diseases had a minimal influence on PH in MBD patients.

Echocardiography

The PH group showed a significantly higher right ventricular diameter, right ventricular outflow tract diameter, main pulmonary artery diameter, left atrial diameter, and interventricular septum thickness compared with the non-PH group (all P< 0.001). The incidence of mitral regurgitation and pericardial effusion was also significantly higher in the PH group compared with the non-PH group (both P< 0.05). However, the ejection fraction was significantly lower in the PH group compared with the non-PH group (P< 0.01). No significant changes in left ventricular diastolic diameter, left ventricular outflow tract, and aortic root dimension were observed between the PH and non-PH groups (all P>0.05). The left ventricular mass index was also not significantly different between the two groups (both P>0.05; Table 4).

Analysis of risk factors for patients receiving MPD complicated by PH

We next examined the risk factors for development of PH using logistic regression analysis of systolic blood pressure, diastolic blood pressure, mean arterial pressure, the proportion of arteriovenous fistula, serum BNP levels, phosphorus levels, CRP levels, albumin levels, hemoglobin levels, hypertensive nephropathy, right ventricular diameter, right ventricular outflow tract diameter, main pulmonary artery, left atrial diameter, interventricular septum thickness, ejection fraction, mitral regurgitation, and pericardial effusion. These factors were found to be significantly different in single factor analysis when comparing the PH group with the non-PH group. A forward conditional logistic regression method was used and showed that the proportion of arteriovenous fistula, CRP levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD (Table 5).

Discussion

This is the first prospective study to analyze patients receiving MPD for complications leading to PH. We found a high occurrence of PH (33.3%) in this cohort of ESRD patients receiving MPD, which is consistent with previous studies reporting similar high incidence rates. One previous study observed a prevalence of PH as high as 30-60% in cohorts and correlated this high incidence with increased mortality and poor renal transplantation outcome (¹⁹19. Kawar B, Ellam T, Jackson C, Kiely DG. Pulmonary hypertension in renal disease: epidemiology, potential mechanisms and implications. Am J Nephrol 2013; 37: 281-290, doi: 10.1159/000348804.
https://doi.org/10.1159/000348804... ). Another study showed that uremic patients receiving chronic dialysis treatment had a high prevalence of PH. This effect was mainly due to elevated pulmonary blood flow and increased pulmonary vascular resistance, which was worsened by fluid overload in hemodialysis patients (²⁰20. Zhao LJ, Huang SM, Liang T, Tang H. Pulmonary hypertension and right ventricular dysfunction in hemodialysis patients. Eur Rev Med Pharmacol Sci 2014; 18: 3267-3273.). PH in CKD patients may be induced by left ventricular disorders and some of the typical risk factors of CKD (²¹21. Bolignano D, Rastelli S, Agarwal R, Fliser D, Massy Z, Ortiz A, et al. Pulmonary hypertension in CKD. Am J Kidney Dis 2013; 61: 612-622, doi: 10.1053/j.ajkd.2012.07.029.
https://doi.org/10.1053/j.ajkd.2012.07.0... ). Leung et al. also demonstrated that variation in PH is largely explained by the degree of pulmonary venous hypertension (²²22. Leung CC, Moondra V, Catherwood E, Andrus BW. Prevalence and risk factors of pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved ejection fraction. Am J Cardiol 2010; 106: 284-286, doi: 10.1016/j.amjcard.2010.02.039.
https://doi.org/10.1016/j.amjcard.2010.0... ). The pathogenesis of PH in ESRD patients might also be due to alterations in endothelial function, increased cardiac output, and myocardial dysfunction, leading to an elevated left heart filling pressure (⁹9. Sise ME, Courtwright AM, Channick RN. Pulmonary hypertension in patients with chronic and end-stage kidney disease. Kidney Int 2013; 84: 682-692, doi: 10.1038/ki.2013.186.
https://doi.org/10.1038/ki.2013.186... ).

To examine the underlying cause of PH in patients receiving MPD, we analyzed clinical data, laboratory indices, and echocardiographic data. We also used echocardiography in the PH and non-PH groups during follow-up visits. We found that smoking, systolic pressure, diastolic pressure, mean arterial pressure and the proportion of internal arteriovenous fistula were significantly higher in the PH group than in the non-PH group. Smoking remains a significant risk factor for lung disease and is also related to PH (²³23. El-Kersh K, Perez RL, Smith JS, Fraig M. Smoking-related interstitial fibrosis (SRIF) and pulmonary hypertension. BMJ Case Rep 2013; 2013: doi: 10.1136/bcr-2013-008970.
https://doi.org/10.1136/bcr-2013-008970... ,²⁴24. Seimetz M, Parajuli N, Pichl A, Veit F, Kwapiszewska G, Weisel FC, et al. Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell 2011; 147: 293-305, doi: 10.1016/j.cell.2011.08.035.
https://doi.org/10.1016/j.cell.2011.08.0... ). Estimated systolic pressure and mean pulmonary arterial pressure are the two main echocardiographic variables used to evaluate PH patients (²⁵25. Pyxaras SA, Pinamonti B, Barbati G, Santangelo S, Valentincic M, Cettolo F, et al. Echocardiographic evaluation of systolic and mean pulmonary artery pressure in the follow-up of patients with pulmonary hypertension. Eur J Echocardiogr 2011; 12: 696-701, doi: 10.1093/ejechocard/jer127.
https://doi.org/10.1093/ejechocard/jer12... ). PH is defined as a mean PAP of at least 25 mmHg at rest (¹⁹19. Kawar B, Ellam T, Jackson C, Kiely DG. Pulmonary hypertension in renal disease: epidemiology, potential mechanisms and implications. Am J Nephrol 2013; 37: 281-290, doi: 10.1159/000348804.
https://doi.org/10.1159/000348804... ). Internal arteriovenous fistula remains the best choice for vascular access in hemodialysis patients (²⁶26. Asano M, Thumma J, Oguchi K, Pisoni RL, Akizawa T, Akiba T, et al. Vascular access care and treatment practices associated with outcomes of arteriovenous fistula: international comparisons from the Dialysis Outcomes and Practice Patterns Study. Nephron Clin Pract 2013; 124: 23-30, doi: 10.1159/000353733.
https://doi.org/10.1159/000353733... ). After successfully creating an arteriovenous fistula, arterial blood flow increases 10- to 20-fold, which is associated with arterial and venous dilation, possibly leading to PH (²⁷27. Allon M, Litovsky S, Young CJ, Deierhoi MH, Goodman J, Hanaway M, et al. Medial fibrosis, vascular calcification, intimal hyperplasia, and arteriovenous fistula maturation. Am J Kidney Dis 2011; 58: 437-443, doi: 10.1053/j.ajkd.2011.04.018.
https://doi.org/10.1053/j.ajkd.2011.04.0... ).

In the current study, laboratory indices showed that BNP, serum phosphorus, and CRP levels were significantly higher in the PH group than in the non-PH group. This finding suggests that these factors might be involved in the development of PH in patients receiving MPD. BNP released from ventricular myocytes is a powerful predictor in cardiovascular disease patients with atrial fibrillation, correlating with higher post-stroke mortality and cardio-embolic stroke (²⁸28. Rost NS, Biffi A, Cloonan L, Chorba J, Kelly P, Greer D, et al. Brain natriuretic peptide predicts functional outcome in ischemic stroke. Stroke 2012; 43: 441-445, doi: 10.1161/STROKEAHA.111.629212.
https://doi.org/10.1161/STROKEAHA.111.62... ). Additionally, elevated serum BNP levels are also reported in acute pulmonary embolism patients (²⁹29. Winkler BE, Schuetz W, Froeba G, Muth CM. N-terminal prohormone of brain natriuretic peptide: a useful tool for the detection of acute pulmonary artery embolism in post-surgical patients. Br J Anaesth 2012; 109: 907-910, doi: 10.1093/bja/aes315.
https://doi.org/10.1093/bja/aes315... ). Plasma BNP has also been reported by many studies as a prognostic indicator in patients with primary PH due to some degree of right ventricular dysfunction (³⁰30. Harbaum L, Hennigs JK, Baumann HJ, Luneburg N, Griesch E, Bokemeyer C, et al. N-terminal pro-brain natriuretic peptide is a useful prognostic marker in patients with pre-capillary pulmonary hypertension and renal insufficiency. PLoS One 2014; 9: e94263, doi: 10.1371/journal.pone.0094263.
https://doi.org/10.1371/journal.pone.009... ,³¹31. Surie S, Reesink HJ, van der Plas MN, Hardziyenka M, Kloek JJ, Zwinderman AH, et al. Plasma brain natriuretic peptide as a biomarker for haemodynamic outcome and mortality following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Interact Cardiovasc Thorac Surg 2012; 15: 973-978, doi: 10.1093/icvts/ivs415.
https://doi.org/10.1093/icvts/ivs415... ). Serum phosphorus levels play an important role in energy production, membrane transport, and signal transduction (³²32. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino RB Sr, Gaziano JM, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007; 167: 879-885, doi: 10.1001/archinte.167.9.879.
https://doi.org/10.1001/archinte.167.9.8... ). However, a report showed no significant differences in serum phosphorus between hemodialysis and PH (³³33. Tarrass F, Benjelloun M, Medkouri G, Hachim K, Benghanem MG, Ramdani B. Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis. Hemodial Int 2006; 10: 356-359, doi: 10.1111/j.1542-4758.2006.00129.x.
https://doi.org/10.1111/j.1542-4758.2006... ). CRP has pro-inflammatory and anti-inflammatory actions, and its pro-inflammatory effects include induction of inflammatory cytokines and tissue factor. The level of CRP correlates with PH and is an independent predictor of PH (³⁴34. Kwon YS, Chi SY, Shin HJ, Kim EY, Yoon BK, Ban HJ, et al. Plasma C-reactive protein and endothelin-1 level in patients with chronic obstructive pulmonary disease and pulmonary hypertension. J Korean Med Sci 2010; 25: 1487-1491, doi: 10.3346/jkms.2010.25.10.1487.
https://doi.org/10.3346/jkms.2010.25.10.... ), as observed in this study.

In the current study, the incidence of PH in hypertensive nephropathy patients was significantly higher than that in non-hypertensive nephropathy patients, indicating that hypertensive nephropathy could lead to the development of PH. Hypertensive nephropathy associated with a progressive decline in glomerular filtration rate, despite reduced blood pressure (³⁵35. Mahajan A, Simoni J, Sheather SJ, Broglio KR, Rajab MH, Wesson DE. Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. Kidney Int 2010; 78: 303-309, doi: 10.1038/ki.2010.129.
https://doi.org/10.1038/ki.2010.129... ), is the second leading cause of complete kidney failure. This condition is associated with significant morbidity and mortality (³⁶36. Hart PD, Bakris GL. Hypertensive nephropathy: prevention and treatment recommendations. Expert Opin Pharmacother 2010; 11: 2675-2686, doi: 10.1517/14656566.2010.485612.
https://doi.org/10.1517/14656566.2010.48... ).

In our study, based on echocardiography results, the right ventricular diameter, right ventricular outflow tract diameter, main pulmonary artery diameter, left atrial diameter, and interventricular septum thickness were significantly higher in the PH group compared with the non-PH group, along with a significantly higher incidence of mitral regurgitation and pericardial effusion in the PH group. However, the ejection fraction was significantly lower in the PH group than in the non-PH group. PH is closely linked with right ventricular dysfunction and left ventricular systolic dysfunction, as well as left-sided valvular disease with chronic elevation in left ventricular filling pressure (³⁷37. Agarwal R, Shah SJ, Foreman AJ, Glassner C, Bartolome SD, Safdar Z, et al. Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction. J Heart Lung Transplant 2012; 31: 467-477, doi: 10.1016/j.healun.2011.11.017.
https://doi.org/10.1016/j.healun.2011.11... ). Ventricular hypertrophy, such as increased ventricular diameter, occurs in response to pressure overload in PH (³⁸38. Piao L, Fang YH, Parikh KS, Ryan JJ, D'Souza KM, Theccanat T, et al. GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: therapeutic implications in pulmonary hypertension. Circulation 2012; 126: 2859-2869, doi: 10.1161/CIRCULATIONAHA.112.109868.
https://doi.org/10.1161/CIRCULATIONAHA.1... ). Our results of logistic regression analysis further confirmed that the proportion of arteriovenous fistula, CRP levels, and ejection fraction are the highest risk factors for PH in patients receiving MPD.

There are some limitations in the present study. First, we used an echocardiogram for the diagnosis of PH, which is not as accurate as right cardiac catheterization (³⁹39. Gavilanes F, Alves JL Jr, Fernandes C, Prada LF, Jardim CV, Morinaga LT, et al. Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension. J Bras Pneumol 2014; 40: 609-616, doi: 10.1590/S1806-37132014000600004.
https://doi.org/10.1590/S1806-3713201400... ). PAP is conventionally evaluated by a right cardiac catheterization procedure. However, in our study, PAP was evaluated by echocardiogram because of the need to perform repeated PAP evaluations over an extended period of time. Additionally, the right cardiac catheterization procedure is traumatic and might affect the patient's compliance with examinations. Second, we used laboratory indices, such as BNP and serum phosphorus, to analyze the potential mechanism of PH in patients receiving MPD. BNP is mainly used as a prognostic indicator for PH patients. The relationship between serum phosphorus and the development of PH is controversial.

Taken together, our results provide an important clinical reference for the risk of PH in patients receiving MPD. Further investigation is likely to reveal early diagnostic and treatment methods in patients receiving MPD, which are urgently needed, as well as the precise mechanisms of development of PH in patients receiving MPD.

Acknowledgments

We would like to thank the director of the Dialysis Center of the Second Affiliated Hospital of Soochow University for his support of our study.

References

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