Pulmonary Hypertension in Hemodialysis Patients

Abstract

Background: Pulmonary hypertension (PH) has been reported to be high among maintenance dialysis patients. There is a paucity of data on the incidence and prevalence of pulmonary hypertension in chronic kidney disease(CKD) in Bangladeshi patients. Materials and Methods: A total 70 CKD patients (male 47,female 23), who were on conservative management and maintenance hemodialysis were studied for the presence of pulmonary hypertension. The variables studied were hypertension, diabetes, duration of dialysis and the hemoglobin, serum creatinine and serum bicarbonate levels. Results: 68.6% of the patients on maintenance hemodialysis had pulmonary hypertension compared to 8.6% of the prediadysis CKD patients. 97.1% of maintenance dialysis patients had anaemia (Hb <10gm/dl) and 42.9% of patients had metabolic acidosis. Conclusion: The incidence of pulmonary hypertension was highest in the hemodialysis group. Significant Pearson’s correlation was found between pulmonary arterial systolic pressure with the duration of hemodialysis, hemoglobin level, serum creatinine, blood sugar and serum bicarbonate level in maintenance hemodialysis patients DOI: http://dx.doi.org/10.3329/cardio.v4i2.10459 Cardiovasc. j. 2012; 4(2): 148-152

Full text

148 Vol.-4, No.-2, January 2012 Cardiovas Journal
Introduction:
Chronic kidney disease (CKD) leads to many co
morbidities that affect patients of all stages of the
disease. The complications of CKD are due to the
disease itself as well as the mode of renal
replacement therapy (RRT). Kidney function can
only be partly replaced by maintenance dialysis,
which provides only 5-10% of excretory renal
function.1 At present out of three modalities of
treatment –conservative management,
hemodialysis (HD) and peritoneal dialysis,
maximum patients are on HD.2 Cardio vascular
morbidity and mortality is highest in the dialysis
population. Recently an association has been found
between RRT and the development of pulmonary
hypertension.
The presence of PH may reflect serious pulmonary
vascular disease, which can be progressive and fatal.
Consequently, an accurate diagnosis of the cause of
PH is essential in order to establish an effective
treatment program. Pulmonary hypertension can
occur from diverse etiologies. The most common
causes of PH are left heart failure and chronic
hypoxic lung diseases. Less commonly, PH occurs
in distinct clinical conditions such as collagen
vascular disease, chronic recurrent
thromboembolism, portal hypertension, human
immunodeficiency virus (HIV) infection,
hematological conditions, following exposure to
drugs and toxins, etc. Regardless of etiology, PH
increases morbidity and mortality. Moreover, the
presence of PH in systemic disorders increases
mortality rates beyond the expected and sometimes
is the leading cause of mortality.
In 1996 Mordechai Yigla first noted unexplained
PH in some long- term hemodialysis (HD) patients
during an epidemiological study of this disorder.
It was assumed that their PH was related to end
stage renal disease (ESRD) or to long term HD
therapy via an arteriovenous (AV) access.
Pulmonary Hypertension in
Hemodialysis Patients
M Moniruzzaman1, MN Islam2, MB Alam3, A.B.M. M Alam3, MMH Khan2,
Z ALI4, AW Chowdhury5, MN Chowdhury6
1Department of Nephrology,United Hospital Limited, Dhaka.2Department of Nephrology, Dhaka
Medical College, Dhaka.3Department of Nephrology, National Institute of Kidney Diseases and
Urology, Dhaka. 4Department of Cardiology, NICVD, Dhaka.5Department of Cardiology, Dhaka
Medical College. 6 Department of Nephrology, National Institute of diseases of the Chest and Hospital
Abstract:
Background: Pulmonary hypertension (PH) has been reported to be high among maintenance
dialysis patients. There is a paucity of data on the incidence and prevalence of pulmonary hypertension
in chronic kidney disease(CKD) in Bangladeshi patients.
Materials and Methods: A total 70 CKD patients (male 47,female 23), who were on conservative
management and maintenance hemodialysis were studied for the presence of pulmonary hypertension.
The variables studied were hypertension, diabetes, duration of dialysis and the hemoglobin, serum
creatinine and serum bicarbonate levels.
Results: 68.6% of the patients on maintenance hemodialysis had pulmonary hypertension compared
to 8.6% of the prediadysis CKD patients. 97.1% of maintenance dialysis patients had anaemia (Hb
<10gm/dl) and 42.9% of patients had metabolic acidosis.
Conclusion: The incidence of pulmonary hypertension was highest in the hemodialysis group.
Significant Pearson’s correlation was found between pulmonary arterial systolic pressure with the
duration of hemodialysis, hemoglobin level, serum creatinine, blood sugar and serum bicarbonate
level in maintenance hemodialysis patients
(Cardiovasc. j. 2012; 4(2): 148-152)
Address of correspondence: Dr Mohammad Moniruzzaman, Specialist, Department of Nephrology, United Hospital
Limited, Gulshan, Dhaka, Bangladesh.
Key words:
Chronic kidney
disease,
Pulmonary
Hypertension,
Haemodialysis.

149 Vol.-4, No.-2, January 2012 Cardiovas Journal
Despite almost five decades of HD therapy via a
surgically created, often large, hemodynamically
significant AV access, the long-term impact of this
intervention on pulmonary circulation has
received little attention. The development of
pulmonary hypertension in ESRD patients is
associated with increased morbidity and mortality.
There is non-invasive technique like Doppler
echocardiography to detect pulmonary
hypertension; so early diagnosis by Doppler
echocardiography enables timely intervention,
currently limited to changing dialysis modality or
referring for kidney transplantation. Even then
there is paucity of data on the incidence and
prevalence of PH in chronic kidney disease in
Bangladeshi patients.
Materials and Methods
This cross-sectional study was carried out in the
Department of Nephrology, Dhaka Medical College
Hospital from January 2010 to December 2010. A
total 70 patients were included in the study out of
which 35 patients on maintenance hemodialysis
& predialysis CKD patients was 35.
All the participants history was taken, physical
examination was done and necessary investigation
was carried out. Blood pressure was recorded at
least after 5 minutes rest being relaxed on a chair
with a support on the back keeping bared arm on
a table at heart level. A conventional
sphygmomanometer was used covering more than
80% of arm by bladder. Patients estimated
glomerular filtration rate (eGFR) was calculated
by using Cockroft-Gault (CG) formula-
[140 –age(yrs)×body wt(kg)]
eGFR=
Serum creatinine (mg/dl)×72
Multiply by 0.85 in female to correct for reduced
creatinine production.
Then all patients have a Doppler echocardiogram
done by an experienced cardiologist. In the
maintenance hemodialysis group the Doppler
echocardiography done on the day after
hemodialysis to overcome the volume overload.
Pulmonary arterial systolic pressure can be
measured non-invasively by tricuspid regurgitation
jet method by Doppler echocardiogram. The aim
is to measure PASP (Pulmonary arterial systolic
pressure) assuming no pulmonary valvular
stenosis, and then this is equal to right ventricular
systolic pressure (RVSP).
RVSP can be easily estimated from the maximum
velocity of the tricuspid regurgitation jet (VTR). The
pressure gradient between the right atrium and
the right ventricle across the tricuspid valve (RVSP-
RAP) can be estimated by the Bernoulli equation
using the maximum VTR.
RVSP-RAP= 4VTR2
The value of RAP (right atrial pressure) is known.
It is equal to the jugular venous pressure (JVP)
which can be assessed clinically (in healthy
individuals and is usually 0-5 cm of blood, measured
from the sternal angle, and 1 cm of blood is almost
equal to 1 mmHg.)
This allows us to estimate that:
PASP= RVSP= 4VTR2+ JVP/or,RAP
For estimation of hemoglobin, serum creatinine,
blood sugar and serum bicarbonate venous blood
samples were collected by sterile disposable
syringe with strict aseptic precaution. For
estimation of blood sugar 2 cc of blood was poured
to blood sugar bottle and 3 cc blood was kept in
syringe for estimation of hemoglobin, serum
creatinine and serum bicarbonate. All samples sent
immediately to clinical pathology, DMCH. Serum
creatinine was estimated using kinetic model; blood
sugar was estimated by Glucose oxidase method.
Echocardiography was done by colour Doppler
Echocardiographic Equipment model GE system
five by GE Vingmed ultrasound, Norway.
The relationship of all the variables to pulmonary
hypertension in CKD was assessed by Pearson’s
correlation coefficient. All data was analyzed by
using computer based SPSS (Statistical Program
for Social Science) program.
Observation and Results
In our study 70 patients were included of whom 35
patients on maintenance hemodialysis and rest 35
patients on predialysis CKD patients which are
categorized as Group I and Group II respectively.
The male/female ratio was almost 2:1.Most of the
patients belongs to 30 to 40 years age range in
both group.
The scatter diagram shows significant relationship
(r=0.424) between pulmonary arterial systolic
Pulmonary Hypertension in Hemodialysis Patients M Moniruzzaman et al.
149

150 Vol.-4, No.-2, January 2012 Cardiovas Journal
pressure (mmHg) with duration of hemodialysis
(months) in group I patients (n=35).
In this study it was found that 68.6% of group I
and 8.6% of group II patients had pulmonary
hypertension. Mild pulmonary hypertension was
found in 22.9%, moderate and severe pulmonary
hypertension was found in 40% and 5.7%
respectively. However only 8.6% patients had mild
pulmonary hypertension in group II patients. The
mean pulmonary arterial systolic pressure (PASP)
was 44.1±14.4 mmHg with range from 28 to 80
mmHg in group I. In group II the mean PASP was
28.9±4.1 mmHg with range from 24 to 38 mmHg.
The mean PASP difference was statistically
significant (p<0.05) in unpaired t-test.
Significant Pearson’s correlation was found
between pulmonary arterial systolic pressure with
the duration of hemodialysis (r=0.424; p=0.023),
hemoglobin level (r=-0.539; p=0.001), serum
creatinine (r=0.568; p=0.001), blood sugar ( r
=0.535; p=0.001) and serum bicarbonate level (r=-
0.470; p=0.003) in group I patients.
In group II patients no correlation were found in
Serum Creatinine, Hemoglobin, Blood sugar and
Serum bicarbonate level with pulmonary arterial
systolic pressure, which were r=0.195; p=0.636,
r=0.199; p=0.251, r=0.161; p=0.326 and r=0.282;
p=0.133 respectively.
Fig 1: Correlation between pulmonary arterial
systolic pressure (mmHg) with duration of
hemodialysis (in months) of the study patients
(n=35)
Table I
Shows mean Pulmonary Arterial Systolic Pressure (mm Hg) distribution of the study patient (n=70).
PASP (mm Hg) Group I(n=35) Group II(n=35) PValue
n%n%
Normal (£30 mmHg) 11 31.4 32 91.4
High (PASP)>30 mmHg
Mild (31-45 mmHg) 8 22.9 3 8.6
Moderate (46-65 mmHg) 14 40.0 0 0.0
Severe (>65 mmHg) 2 5.7 0 0.0
Mean+SD 44.1 ±14.4 28.9 ±4.1 0. 001S
Range (min - max) (28 -80) (24 -38)
S= Significant
P value reached from unpaired ‘t’ test
Table-II
Correlation of different parameters with pulmonary arterial systolic pressure
of the study patients (n=70)
Group I(n=35) Group II(n=35)
Correlation P value Correlation P value
coefficient coefficient
Duration of hemodialysis in (months) 0.424 0.023s--
Hemoglobin (gm/dl) -0. 539 0.001s0.199 0.251ns
Serum Creatinine (mg/dl) 0.568 0.001s0.195 0.636ns
Blood sugar 2h ABF (mmol/L) 0.535 0.001s0.161 0.326ns
Serum bicarbonate level (mmol/L) -0.470 0.003s0.282 0.133ns
p value reached from Pearson’s correlation
Cardiovascular Journal Volume 4, No. 2, 2012
150

151 Vol.-4, No.-2, January 2012 Cardiovas Journal
Disscusion:
An echocardiography diagnosis of pulmonary
hypertension (PH) is made when systolic
pulmonary arterial pressure (PAP) exceeds normal
values (30mmHg). In mild PH, values ranges up
to 45 mmHg, in moderate PH, PAP is between 45
and 65 mmHg and in severe PH, PAP values are
greater than 65 mmHg. Systolic PAP equals
cardiac output times pulmonary vascular
resistance (PVR), (i.e., PAP=cardiac output ×PVR).
Increased cardiac output by itself does not cause
PH because of the enormous capacity of the
pulmonary circulation to accommodate the
increase in blood flow. Therefore development of
PH requires marked elevation of pulmonary
vascular resistance.
There are several potential explanations for the
development of PH in patients with ESRD.
Hormonal and metabolic derangement associated
with ESRD might lead to vasoconstriction of
pulmonary vessels and increased pulmonary
vascular resistance.3 Values of PAP may be further
increased by high cardiac output resulting from
the AV access itself,4 worsened by commonly
occurring renal anemia and fluid overload. Medical
conditions with shunting of blood from the left to
the right side of the heart and increased cardiac
output and pulmonary blood flow, such as
congenital heart disease, are well recognized as
possible causes of PH.5,6
Excess mortality rates due to cardiovascular
disease in end-stage renal disease (ESRD) patients
had been described by epidemiological and clinical
studies. It accounts for approximately 50 percent
of deaths in dialysis patients. Although
controversial, this may be due in part the presence
of excess vascular calcification, particularly in the
form of extensive coronary artery calcification,
which can be observed even in very young dialysis
patients. It was suggested that abnormalities of
the right ventricular function in patients with
ESRD were largely due to pulmonary
hypertension, which usually develops secondary
to pulmonary artery calcifications.7
In the present study it was observed that the mean
age was 39.5±10.3 years and 42.5±12.8 years in
group I and II respectively (p>0.05). Male was
predominant in both groups and male female ratio
was almost 2:1 in the whole study patients.
HTN was observed in 85.7% and 71.4% in group I
and group II respectively (p =0.145). DM was
present 20.0% in group I and 22.9% in group II (p
= 0.770).
Majority (42.9%) of the patients had 13 – 24 months
of hemodialysis and the mean duration of
hemodialysis was 22.9±10.4 months with range
from 6 to 36 months.
Pulmonary hypertension was found 68.6% (24) on
maintenance hemodialysis patients whereas only
8.6% (3) in predialysis CKD patients. The mean
systolic pulmonary arterial pressure (PAP) was
44.1±14.4 mmHg with range from 28 to 80 mmHg
in group I. In group II the mean systolic PAP was
28.9±4.1 mmHg with range from 24 to 38 mmHg.
The mean systolic PAP was significantly (p<0.05)
higher in group I patients.
In this study it was observed that 97.1% and 74.3%
patients had anaemia (<10gm/dl hemoglobin) in
group I and group II respectively (p = 0.001). The
mean hemoglobin was 8.7±0.7 gm/dl in group I and
9.5±0.9 gm/dl in group II (p = 0.001).
The mean serum creatinine was 9.4±1.5 and 5.1±1.3
mg/dl in group I and group II respectively. The
mean blood sugar 2h ABF was 6.7±1.2 mmol/L in
group I and 5.6±0.3 mmol/L in group II. The mean
hemoglobin level was significantly (p<0.05) higher
in group II but the mean S. creatinine and blood
sugar 2h ABF were significantly (p<0.05) higher
in group I.
Regarding the serum bicarbonate level 42.9% and
17.1% in group I and group II patients had
metabolic acidosis, which was significant (p<0.05)
between the two groups.
In group I patients significant Pearson’s correlation
were found between pulmonary arterial pressure
with duration of hemodialysis (r=0.424; p=0.023),
hemoglobin level (r=-0.539; p=0.003) creatinine
(r=0.568; p=0.001) blood sugar (2h ABF) (r=0.535;
p=0.001) and serum bicarbonate level (r=-0.470;
p=0.001,).
In group II patients no significant correlation were
found between pulmonary arterial pressure with
hemoglobin level, creatinine, blood sugar (2h ABF)
and serum bicarbonate level.
The study demonstrates that CKD patients on
maintenance hemodialysis are significantly more
likely to develop pulmonary hypertension.
Pulmonary Hypertension in Hemodialysis Patients M Moniruzzaman et al.
151

152 Vol.-4, No.-2, January 2012 Cardiovas Journal
Conclusion:
This study demonstrated that 68.6% of patients
with CKD on MHD have PH which is much higher
value compared to other study. The sample size of
this study is relatively small, and for this reason,
multicenter studies are required. PAP was non-
invasively measured by Doppler echocardiography
without right heart catheterization. Since follow-
up of this study was not done to evaluate the effect
of pulmonary hypertension on morbidity and
mortality, long-term follow-up of patients with
pulmonary hypertension is needed.
References:
1. Gokul R. Replacement therapy by dialysis. In:
Weatherall DJ, Ledingham JG, Warrell DA. Eds. Oxford
textbook of medicine, 3rd ed. Oxford;Oxford University
Press, 1996: 3306- 3310.
2. Yigla M, Dabbah S, Azzam ZS, Rubin AH. Reisner SA:
Background diseases in 671 patients with moderate to
severe pulmonary hypertension. Isr Med Assoc J 2000;
2: 684-689.
3. Moris ST, Jardine AG. The vascular endothelium in
chronic renal failure. J Nephrol 2000; 13: 96-105.
4. Savage MT,Ferro CJ, Sassano A, Thomson CR. The
impact of arterious fistula formation on central
hemodynamic pressure in chronic renal failure
patients:a prospective study. Am J kidney Dis 2002; 40:
753-759.
5. Dschietzig T, Richter C, Bartsch C, Bohme C, Heinze
D, Ott F, Zartnack F, Baumann G, Stangl K. Flow-
induced pressure differentially regulates endothelin-
1urotensin 11, adrenomedullin, and relaxin in
pulmonary vascular endothelium. Biochem biophys res
commun 2001, 89 :245-251.
6. Michel RP, Hakim TS, Hanson RE, Dobell AR, Keith F,
Drink water D. Distribution of lung vascular resistance
after chronic systemic-to-pulmonary shunts. Am J
Physiol 1985; 249: 1106-1113.
7. S Mahdavi-Mazdeh M, Alijavad-Mousavi S, Yahyazadeh
H, Azadi M, Yoosefinejad H, Ataiipoor Y. Pulmonary
Hypertension in Hemodialysis Patients. Saudi J Kidney
Dis Transpl 2008; 19 :189-193.
8. Dagli CE, Sayarlioglu H, Dogan E, Acar G, Demirpolat
G, Ozer A, Koksal N, Gelen ME, Atilla N, Tanrikulu
AC, Isik IO, Ugur T. Prevalence of and Factors Affecting
Pulmonary Hypertension in Hemodialysis Patients.
Respiration 2009; 78 : 411–415.
9. Floege Jurgen and Ketteler M. Vascular calcification in
patients with end-stage renal disease. Nephrol Dial
Transplant 2004; 19 : V59-v66.
10. Galie N, Torbicki A, Barst R, Dartevelle P, Hawotrh S.
Guidelines on diagnosis and treatment of pulmonary
arterial hypertension. European Heart Journal 2009;
30 : 2493-2537.
11. Nakhoul F, Yigla M, Gilman R, Reisner SA, Abassi Z.
Pathogenesis of pulmonary hypertension in
haemodialysis patients via arterio-venous access.
Nephrol Dial Transplant 2005; 20 :1686–1692.
12. Pastan S, Bailey J. Dialysis therapy. N Engl J Med
1998; 338 :1428-1437.
13. Patel P, G. Abraham, B. Pratap, R. Ramalakshmi, M.
Mathew, J. M. Jeevan, T. R. Muralidharan, A. Moorthy,
N. Leslie. Clinical and biochemical parameters in chronic
kidney disease with pulmonary hypertension. Indian
Journal of Nephrology 2007;17 : 4-6.
14. Tarrass F, Benjelloun M, Hachim K, Benghanem MG,
Ramdani B. Pulmonary hypertension in patients with
end-stage renal disease. Indian J Nephrol 2005; 15 :
223-226.
15. Tarrass F, Benjelloun M, Medkouri G, Hachim K,
Benghanem MG, Ramdan B. Doppler echocardiograph
evaluation of pulmonary hypertension in patients
undergoing hemodialysis. Hemodialysis International
2006; 10 : 356–359.
16. Yigla M, Abassi Z, Reisner SA and Nakhoul
F.Pulmonary Hypertension in Hemodialysis Patients:
An Unrecognized Threat. Seminars in Dialysis 2006;
19 : 353–357.
17. Yigla M, Keidare Z, Safadi I, Tov N, Reisner SA,
Nakhoul F. Pulmonary calcification in hmodialysis
patients: correlation with pulmonary artery pressure
values. Kidney Int 2004; 66 : 806-810.
Cardiovascular Journal Volume 4, No. 2, 2012
152