Prevalence and factors associated with Pulmonary Arterial Hypertension on maintenance Hemodialysis Patients in Kinshasa, the Democratic Republic of the Congo

Background: Cardiovascular diseases in particular Pulmonary arterial hypertension (PAH) is associed a high morbi-mortality in chronic hemodialysis, but it’s magnitude remains paradoxically unknown in sub-Saharan Africa. The aim of this study was to evaluate the prevalence of PAH and associated factors in chronic hemodialysis patients. Patients and method: In a cross-sectional study, patients treated with HD for at least 6 months in 4 hemodialysis centers were examined. PAH was defined as estimated systolic pulmonary arterial pressure (sPAP) ≥ 35 mmHg using transthoracic Doppler echocardiography performed 24 hours after the session. Results: A total of 85 HD patients were included. Their average age was 54.6 ± 14.3 years. 57 patients (67.1%) were male. Mean duration of HD was 13.3 ± 11 months. With reference to vascular access, 12 (14.1%), 29 (34.1%) and 44 (51.8%) patients had AVF, tunneled cuff and temporary catheter, respectively. The underlying cause of ESRD was diabetes in 30 patients (35.3%). The prevalence of PAH was 29.4%. In multivariate analysis, no secure healthcare funding (adjusted OR 5, 95% CI [1.24-8.27]), hyponatremia (adjusted OR 2, 95% CI [1.61-10.01]), arrhythmia (aOR 3, 95% CI [1.06 -5.85]), vascular access change (aOR 4, 95% CI [1.12-6.23]) and diastolic dysfunction (aOR 5, 95% CI [1.35-9.57] were independently associated with PAH. Conclusion: One third of hemodialysis patients exhibit PAH, which is associated with diastolic dysfunction and arrhythmia. Therefore, early detection and control of PAH and associated factors may help to tackle PAH associated morbidity and mortality in maintenance hemodialysis patients.


Introduction
Excessive cardiovascular mortality in patients with end-stage renal disease (ESRD) has been described in epidemiological and clinical studies. It accounts for about 50% of deaths in dialysis [1] of which about 29 -30 % due to pulmonary hypertension [2]. Pulmonary arterial hypertension (PAH), defined as a rise in pulmonary arterial pressure (PAP) resulting from heart, lung or systemic disorders, is a common finding in patients on maintenance hemodialysis [3,4] and an independent predictor of all-cause and cardiovascular mortality in maintenance hemodialysis patients [5 -8]. The prevalence of PHT varies from 30 to 40%, as detected by Doppler echocardiography in patients on chronic hemodialysis (HD). Several studies have reported PAH-related mortality: "The Jackson Heart Study" on 27% of patients with PAH hospitalized for heart failure for an average of 6 years, had a death rate of 44% [9]. Once PAH was established, it is associated with high morbidity and mortality [10], in a large prospective study in patients with chronic renal failure who were not dependent on dialysis, PAH was associated with a risk of 15% death and 28% cardiovascular events while hemodialysis is recognized as a factor that promotes the occurrence of PAH [11].
The possible causes of PAH in haemodialysis patients are classified into three categories: 1) an increase in cardiac output caused by arteriovenous fistula, anemia or hypervolemia [12,13]; 2) increased pulmonary vascular resistance caused by uremia-induced endothelial dysfunction, pulmonary embolism, calcification of the pulmonary artery or other comorbid diseases, including chronic obstructive pulmonary disease or connective tissue disease, and 3) elevation of pulmonary capillary pressure caused by systolic and diastolic heart failure [14]. Barak and Katz's hypothesized that microbubbles, which originate from the dialysis tubes or filter, may be trapped in the pulmonary circulation [15]. Early intervention to reduce pressure in the pulmonary artery can prevent the worsening of heart failure and death [16][17][18][19]. The purpose of this study was to evaluate the prevalence, associated characteristics and determinants of PAH in chronic hemodialysis patients.

Study design and participants
This present study was a cross-sectional one conducted from Mars 2016 to June 2019 and included ESRD patients ≥18 years old on maintenance HD for more than 6 months in 4 hemodialysis centers (University Hospital of Kinshasa, Ngaliema Medical center, Afia Medical Care, Medical Center of Kinshasa). ESRD was defined as irreversible and advanced loss of kidney function due to any etiology requiring long term RRT with HD. Patients on chronic hemodialysis with the following characteristics: chronic pulmonary diseases such as chronic obstructive pulmonary disease, pulmonary fibrosis, pregnant patients, pregnant women, chest wall, previous pulmonary embolism, collagen vascular disease, moderate or severe mitral or aortic valve disease and having obstructive sleep apnea syndrome were excluded from the study.

Hemodialysis method
Patients had two or three sessions per week for 24 hours with anticoagulant (low molecular weight heparin or unfractionated heparin) at each session. Most patients were treated with synthetic dialyser membranes (high flux) and bicarbonate-based dialysis solution at a bicarbonate concentration of 32 mEq / L. Blood flow and dialysate flow rate were 200, respectively at 400 mL / min and 500-800 mL / min, with the generators 4008 and 5008s of Fresenius.

Echocardiographic measurements
Transthoracic Doppler echocardiograms were performed by a single cardiologist using an ultrasound system with a 3.5 Hz cardiac lead (Vivid 7, GE, Massachusetts, USA) as a noninvasive method, in post dialysis, 24 hours after when patients were at optimal dry weight. PHT was defined as Systolic PAP equal to or greater than 35 mm Hg. Systolic right ventricular (or pulmonary artery) pressure was calculated using the modified Bernoulli equation: PAP = tricuspid systolic jet (TR) + 10-15 mm Hg (estimated right atrial pressure: 15 mm Hg in dilated right atrium and 10 mmHg in normal or slightly enlarged right atrium) [20]. The parameters of interest included the following: age, sex, comorbidities, medications, etiology of kidney disease, age at time of ESRD, duration of hemodialysis therapy, and blood access location. Laboratory investigations encompassed: blood urea nitrogen (BUN), serum creatinine, natremia, kaliemia, uric acid, hemoglobin, hematocrit, iron, ferritin, ProBNP, Troponin, calcium, phosphorus, and parathyroid hormone level. The results of the predialysis blood samples at the time of echocardiographic study and the mean of the preceding three months values were evaluated.

Statistical Analysis
Data was collected on an ad hoc file and analyzed using SPSS version 21. Normally distributed continuous variables are expressed mean ± standard deviation; categorical variables as absolute (n) and relative (in percent) frequencies. Student t test was used to compare of two groups; Chi square test was used to compare frequencies of categorical variables. Logistic Regression analysis was used to assess the determinants of PAH. P value<0.05 was considered significant.

Ethical issues
The research followed the tenets of the Declaration of Helsinki and informed consent was
In logistic multivariate analysis (

Discussion
The main findings of the present study are as follows. First, roughly 3 out of 10 patients on maintenance hemodialysis had PAH. Second, hyponatremia, arrhythmia, vascular access change, diastolic dysfunction and no secure healthcare funding emerged as the main factors associated with PAH.
One third of patients on maintenance hemodialysis exhibited PAH. This frequency is within the range of 27-57% reported by most studies [21,22] and similar to that reported by Amin et al. in Egypt although echocardiography was performed within 4h after the end of dialysis [16]. However, it is lower than that of 58.6% and 60% found by Fabian in Italy [23] and The independent determinants of pulmonary arterial hypertension in our study were: unsecured funding for dialysis, hyponatremia, arrhythmia, vascular access first change, and diastolic dysfunction. The positive association of unsecured funding with PAH is a reflection of irregular dialysis sessions with subsequent significant interdialytic weight gain through renal sodium and water retention [23]. Sodium and water retention and subsequent hemodilution could also explain hyponatremia and its association with PAH.
The vascular access change, most often from catheter to more efficient vascular access such as arteriovenous fistula aggravates the pulmonary congestion through increased circulating blood volume. Indeed, PAP may also be increased by high cardiac output resulting from the arteriovenous access and/or concomitant renal anemia, as well as from   Prevalence of PAH