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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2013  |  Volume : 24  |  Issue : 5  |  Page : 925-929
Progressive pulmonary hypertension: Another criterion for expeditious renal transplantation

1 Department of Nephrology, Madras Medical Mission, Chennai, India; Department of Internal Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
2 Department of Nephrology, Madras Medical Mission, Chennai, India

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Date of Web Publication12-Sep-2013


The aim of this retrospective study was to compare the prevalence of pulmonary hypertension in a cohort of patients with end-stage renal disease (ESRD) prior to and following renal transplantation and to identify the possible risk factors. Of the 425 renal transplantations performed between 2001 and 2007, Doppler echocardiographic findings were available in 124. The echocardiographic data, collected both pre- and post-transplant, included the pulmonary artery pressure (PAP), ejection fraction and left ventricular hypertrophy. The data analyzed included age, gender, hypertension, diabetes, smoking status, along with blood urea, creatinine, glomerular filtration rate, hemoglobin, hemodialysis duration, urine albumin, arterio-venous access and body mass index (BMI). Chi-square test was used for discrete variables and ANOVA was used for continuous variables. Of the patients studied, males comprised 72%; the mean age was 43.3 ± 13.02 years; 87% were hypertensive, 30% were diabetic and 4% were smokers. Statistical analysis revealed a significant reduction of the PAP, irrespective of its severity, following renal transplantation (P <0.05). The PAP had no significant correlation with any of the parameters analyzed, with the exception of BMI (P <0.05). Our study suggests that the PAP gets reduced in patients with ESRD after renal transplantation.

How to cite this article:
Reddy YN, Lunawat D, Abraham G, Matthew M, Mullasari A, Nagarajan P, Reddy YN. Progressive pulmonary hypertension: Another criterion for expeditious renal transplantation. Saudi J Kidney Dis Transpl 2013;24:925-9

How to cite this URL:
Reddy YN, Lunawat D, Abraham G, Matthew M, Mullasari A, Nagarajan P, Reddy YN. Progressive pulmonary hypertension: Another criterion for expeditious renal transplantation. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2020 Jul 4];24:925-9. Available from: http://www.sjkdt.org/text.asp?2013/24/5/925/118080

   Introduction Top

Very little is known about pulmonary hypertension (PHT) in patients with end-stage renal disease (ESRD) and renal transplant recipients. PHT is an elevation of the pulmonary arterial pressure (PAP), and, in the setting of ESRD, it is believed to be caused by increased pulmonary blood flow, which is at least in part due to the hyperdynamic circulation created by the arterio-venous (AV) fistula used for hemodialysis (HD). Recently, imbalance of vasoconstrictors and endothelium-derived nitric oxide has been implicated as well, and the evidence for this pathway lies in the successful reversal of PHT with the use of the endothelin antagonist, bosentan. [1],[2] There is vasoconstriction and obliteration of the lumen of small vessels in the lungs by the formation of plexiform lesions due to dysregulation of endothelial growth and angiogenesis in response to local triggers. This results in increased resistance to flow. [3],[4] The morbidity and mortality that results from PHT is extremely high.

There are several potential explanations for the development of PHT in patients with ESRD. Hormonal and metabolic derangements associated with ESRD might lead to pulmonary arterial vasoconstriction and an increase in the pulmonary vascular resistance. [5] PAP may further be increased by high cardiac output resulting from the AV access itself, worsened by the frequently occurring anemia and fluid overload. [5]

We have recently shown a 24% incidence of PHT as detected by Doppler echocardiography in patients with ESRD. Successful kidney transplantation caused a significant fall in the PAP values. Based on these data, we presumed that excessive pulmonary blood flow is involved in the pathogenesis of the disease, which again could be related to various factors.

The current study was carried out to assess the prevalence and risk factors for PHT in a population of patients with ESRD and its outcome after transplantation.

   Subjects and Methods Top

This study was approved by the clinical research ethics review board of our institution.

Patient selection

This retrospective analysis of renal transplant recipients was conducted in a tertiary care hospital in South India. Data were collected from a cohort of 425 patients between 2001 and 2007. The PAP was compared pre- and post-transplantation. Patients with potential causes for secondary pulmonary hypertension, like chronic obstructive pulmonary disease and asthma, were excluded from the study.

Patient evaluation

Systolic PAP, estimated in the 124 patients by Doppler echocardiography both pre- and post-transplantation, was noted. To avoid overesti-mation of the PAP values due to volume overload, the echocardiographic studies in patients on HD were performed within 1 h after completion of HD. For making comparisons, the last echocardiographic finding prior to transplantation and the first echocardiographic finding after transplantation was taken into account.

An experienced operator performed all the echocardiographic studies. A complete two-dimensional, M-mode and Doppler echocardiographic study was obtained from each patient. A tricuspid systolic jet was recorded from the parasternal or apical window with a continuous-wave Doppler probe. Systolic right ventricular (or pulmonary artery) pressure was calculated using the modified Bernouli equation: PAP = 4 × (tricuspid systolic jet) + 10 mmHg (estimated right atrial pressure).

PHT was defined as a systolic PAP of >35 mmHg. The severity of PHT was classified as follows: Mild PHT: >35 and ≤45 mmHg, moderate PHT: >45 and ≤55 mmHg, moderately severe PHT: >55 and ≤60 mmHg and severe PHT: >60 mmHg.

The general data concerning the study patients were collected and included the following: Age, sex, hypertensive status, diabetic status and smoking status along with blood urea, creatinine, glomerular filtration rate (GFR-by Nankivel formula), hemoglobin, HD duration, urine albumin, body mass index (BMI), AV access (present or absent), ejection fraction (EF) and left ventricular hypertrophy (LVH). All data were collected both pre- and post-transplantation.

   Statistical Analysis Top

Statistical analysis was performed using SPSS Software for Windows. Pulmonary artery pressures and other continuous variables were compared between patients prior to and post-transplantation using ANOVA. Comparison of other variables was made between those with and those without PHT pre-transplant using the chi square test for discrete variables and ANOVA for continuous variables. Values were expressed as mean ± 1 SD. All P-values <0.05 were considered significant.

   Results Top

Data of the study patients (n = 425) including 72% males and 28% females with a mean age of 43.3+/- 13.02 years (range 11-70 years) are given in [Table 1]. [Figure 1] and [Figure 2] show the PAP findings prior to and following transplantation, respectively.
Table 1: Data regarding age, sex, hypertension, diabetes, smoking, duration on dialysis and presence of arterio-venous fistula in the study patients post-transplantation (N = 425).

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Figure 1: Data regarding the presence of pretransplant pulmonary artery hypertension in the study patients.

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Figure 2: Data regarding the presence of posttransplant pulmonary hypertension in the study patients.

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The mean and the range of various variables like creatinine, blood urea, GFR, hemoglobin, BMI (all post-transplant) and EF (both pre- and post-transplant) are given in [Table 1].

Few echocardiographic parameters were compared pre- and post-renal transplantation. There was no significant change in the EF (P-value >0.05). There was a significant reduction in the PAP following renal transplantation (P = 0.00). [Table 2] is a tabular representation of pre- and post-transplant PHT. Of the 71.8% patients with no pre-transplant PHT (≤35 mmHg), 67.7% remained normal following transplantation, 2.4% developed mild PHT and 1.6% developed moderate PHT. Of the 13.7% patients with mild pre-transplant PHT (>35 and ≤45 mmHg), 8.9% developed normal PAP, 4% had mild PHT and 0.8% had moderate PHT following transplantation. Among the 11.3% patients with moderate pre-transplant PHT (>45 and ≤55 mmHg), 6.5% had normal PAP and 2.4% each had mild and moderate PHT, respectively, following transplantation. Of the 3.2% who had severe pre-transplant PHT (>60 mmHg), 0.8% had normal PAP, 1.6% moderate and 0.8% had severe PHT post-transplantation. There were no patients with moderately severe PAH (>55 and ≤60 mmHg) in this study.
Table 2: Pre- and post-transplant pulmonary artery hypertension in the study patients.

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The collected variables were compared between patients with and without pre-transplant PHT. There was no significant correlation between the hypertensive status of a patient and pre-transplant PHT. The age, sex, smoking status of a patient, diabetic status, patient's hemoglobin, blood urea, GFR, HD duration, presence or absence of AV fistula and urine albumin also did not have any correlation with pre-transplant PHT. It was noted that BMI had a significant correlation (P <0.05) with the presence of pre-transplant PHT.

   Discussion Top

The data presented above and the statistical analysis clearly reveal a significant decline in the PAP following renal transplantation. There was no statistical significance achieved when the presence of PHT was compared with age, gender, smoking status, diabetic status, hypertensive status, hemoglobin, creatinine, blood urea, urine albumin, HD duration, GFR and presence of AV fistula of the patients. In other words, none of these clinical, hemodynamic and metabolic variables had significantly affected our cohort's systolic PAP both prior to and following transplantation.

Alekseevskilch and Kolybin studied the development of PHT in patients with ESRD who were maintained on regular HD. Successful renal transplantation resulted in late post-operative reduction of pulmonary artery hypertension, as was seen in our study population also. This finding suggested the possibility of a reversible cause of PHT in these patients. [6]

One of the limitations of our study was the absence of data on PTH, serum calcium and phosphorus levels, as secondary hyperparathyroidism has been implicated in the pathogenesis of PHT. Akmal et al examined the role of chronic excess of parathyroid hormone in the genesis of pulmonary artery calcification and proposed that PHT developed secondary to pulmonary artery calcification. [7] The other suggested mechanisms for developing PHT in patients with ESRD include sleep apnea, increased cardiac output and subsequent increased pulmonary flow due to anemia and the presence of AV fistula. AV shunts created for HD have been identified as a cause of unexplained PHT in patients with ESRD. Yigla and Bozbas et al had concluded that long-term HD via AV access may be involved in the pathogenesis of PHT by affecting pulmonary vascular resistance and cardiac output. [8] , [9] We, however, did not find any association between anemia or AV fistula and the development of PHT, suggesting that hyperdynamic circulation from these factors may not be a significant contributor to PHT in our South Asian population.

In yet another study, Yigla et al mentioned that pulmonary hypertensive disease of HD patients is a unique form of PHT in which elevated cardiac output and uremia-induced endothelial dysfunction exist. PAP and cardiac output decrease significantly after successful transplantation. Because the PAP reduced comparably in kidney recipients irrespective of whether the fistula was opened or closed, these data suggest that non-hemodynamic factors may be involved in the beneficial effects of renal transplantation. These factors may include improvement in the inflammatory status following immunosuppressive therapy as well as modulation of cytokines, toxins, vascular remodeling and endothelial dysfunction. [10]

   Limitations of the Study Top

PAP was non-invasively measured by Doppler echocardiogram without obtaining direct invasive measurements. However, measurement of PAP by the applied Doppler echocardiographic method has been reported to have an excellent correlation with measurements obtained by invasive methods. Pulmonary function tests were not performed and, therefore, the relationship between respiratory function and PHT as well as calcification were not evaluated. Because this was a retrospective study, Doppler echocardiographic findings were not available for all the 425 patients.

   Conclusion Top

Based on these observations, we can conclude that a large number of patients with ESRD have concomitant PHT that can be ameliorated, if not totally reversed, by renal transplantation. Longstanding PHT of any etiology is associated with anatomic changes in pulmonary capillaries and right ventricle with increased morbidity and mortality. [11],[12] Estimation and follow-up of PAP should be performed in all patients with ESRD. This study reiterates the fact that significant progressive PHT in patients with ESRD is another criterion for expeditious transplantation.

   References Top

1.Archer S, Rich S. Primary pulmonary hypertension: A vascular biology and translational research 'work in progress'. Circulation 2000; 102:2781-91.  Back to cited text no. 1
2.Yigla M, Dabbah S, Azzam ZS, Rubin AH, Reisner SA. Background disease in 671 patients with moderate to severe pulmonary hypertension. Isr Med Assoc J 2000;2:684-9.  Back to cited text no. 2
3.Rubin LJ. Pathology and pathophysiology of primary pulmonary hypertension. Am J Cardiol 1995;75:51-4A.  Back to cited text no. 3
4.Jeffery TK, Morrell NW. Molecular and cellular basis of pulmonary vascular remodelling in pulmonary hypertension. Prog Cardiovasc Dis 2002;45:173-202.  Back to cited text no. 4
5.Abassi Z, Nakhoul F, Khankin E, Reisner SA, Yigla M. Pulmonary hypertension in chronic dialysis patients with arteriovenous fistula: Pathogenesis and therapeutic perspective. Curr Opin Nephrol Hypertens 2006;15:353-60.  Back to cited text no. 5
6.Alekseevskilch IuG, Kolybin VS. Morphology of the lesser circulation during programmed hemodialysis and the transplantation of a human cadaveric kidney. Arkh Patol 1988;50:60-6.  Back to cited text no. 6
7.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.  Back to cited text no. 7
8.Yigla M, Nakhoul F. Pulmonary hypertension in patients with end-stage renal disease. Chest 2003;123:1577-82.  Back to cited text no. 8
9.Bozbas SS , Akcay S, Altin C, et al. Pulmonary hypertension in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc 2009;41:2753-6.  Back to cited text no. 9
10.Nakhoul F, Yigla M, Gilman R, Reisner SA, Abassi Z. The pathogenesis of pulmonary hypertension in hemodialysis patients via arteriovenous access. Nephrol Dial Transplant 2005;20:1686-92.  Back to cited text no. 10
11.D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Am Intern Med 1991;115:343-9.  Back to cited text no. 11
12.Rich S. Primary pulmonary hypertension. Prog Cardiovasc Dis 1998;31:205-38.  Back to cited text no. 12

Correspondence Address:
Yogesh N.V. Reddy
Department of Nephrology, Madras Medical Mission, Chennai, India

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DOI: 10.4103/1319-2442.118080

PMID: 24029256

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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