European Journal of Cardiovascular Medicine

Chronic kidney disease (CKD) includes a spectrum of pathophysiologic processes associated with abnormal kidney function and progressive decline in glomerular filtration rate (GFR). There are different stages of CKD which are stratified by both estimated GFR and the degree of albuminuria ¹. The prevalence of CKD is increasing worldwide. Most common cause of CKD in Europe and north America is diabetic nephropathy secondary to type 2 diabetes mellitus ¹. Since CKD increases the mortality and morbidity risks, they have become a major public health problem². The population of India is more than one billion which is projected to become the major reservoir of chronic diseases like diabetes mellitus and hypertension³. 25–40% of them are likely to develop CKD, thereby ESRD burden will rise, and the health-care system would need to take care of these individuals².The prevalence of CKD in different regions ranges from <1% to 13% and recently, data from the International Society of Nephrology’s Kidney Disease Data Center Study reported a prevalence of 17% ⁴. There is 10 – 200-fold increase risk of cardiovascular disease among CKD patients depending upon stages compared to general population which is highest in ESRD patients ¹. So, focus of patient care in earlier stages should be directed to prevention of cardiovascular complications. The major structural cardiac anomaly in patients with CKD is left ventricular hypertrophy (LVH) and is associated with increased risk for cardiac ischemia, congestive heart failure, and a strong independent predictor of cardiovascular mortality. Most of them with CKD die due to cardiovascular events before reaching ESRD due to both traditional and non-traditional risk factors⁵. Anemia and hypertension are consistently associated with cardiac failure, a pre-lethal occurrence that predated two thirds of all dialysis patients’ death ⁶. Other CVS complications include regional wall motion abnormality, congestive heart failure, pericardial effusion, valvular calcification. Pulmonary hypertension is a recently recognised complication in ESRD patients ².

There are various complications enlisted among CKD patients which are due to the disease per se and also due to the mode of RRT (Renal Replacement Therapy). There are 3 modalities of treatment namely conservative management, hemodialysis (HD), peritoneal dialysis (PD) ³. Hemodialysis is a form of renal replacement therapy that relies on the principles of solute diffusion across a semipermeable membrane; during which metabolic wastes including creatinine, urea, excess water and salt are removed. Approximately 85% patients are on HD ¹. It has also been found that patient on HD is at highest risk for cardiovascular morbidity and mortality⁷.

There is an association found between hemodialysis and the development of pulmonary hypertension (PH) which is estimated to be around 19-69% and ESRD with PH is 9-39% ⁸. Normal pulmonary artery pressure at sea level has a peak systolic value of 18-20 mmHg. Definite pulmonary hypertension is present when pulmonary artery systolic and mean pressures exceed 35 and 20mmHg, respectively. Pathogenesis of renal failure associated with PH is complex, and it may include metabolic and hormonal derangements, high cardiac output due to arterio-venous fistula (AVF), impaired endothelial function, anemia, fluid overload, and other factors ⁹.

Pulmonary hypertension is an independent predictor of increased mortality in patients on hemodialysis and those undergoing kidney transplantation, which is less likely seen in other stages of CKD. It is therefore important to detect the presence of pulmonary hypertension among patients undergoing hemodialysis. Further, detecting the presence of PH among patients secondary to RRT who are due for transplantation will guide us about the overall prognosis in the post-transplant period. The data regarding PAH among patients with long term hemodialysis from India is scarce, hence we will study the prevalence of pulmonary hypertension among non-dialysis and dialysis dependent chronic kidney disease patients.

 AIMS AND OBJECTIVE:

1. To study the prevalence of pulmonary hypertension (PH) in CKD patients.

2.Compare prevalence of pulmonary hypertension in dialysis dependent and independent CKD patients.

Source of data: The study was conducted among non – dialysis and dialysis dependent CKD patients coming to Department of General Medicine & Nephrology of M.K.C.G. Medical College and Hospital, Berhampur between the time period April 2021 to March 2023. Here hemodialysis patients were included. Sample size:120 CKD patients (60 non-dialysis and 60 dialysis dependent) of age ≥18 years were taken. Study type: Cross Sectional Study

Inclusion criteria: All CKD patients (both on HD and conservative management) of age 18 years were included.

Exclusion criteria: Primary pulmonary hypertension, Chronic obstructive and restrictive lung disease, Ischemic heart disease, Chronic pulmonary thromboembolism, Valvular heart disease, Chronic liver disease, Sickle cell disease and Congenital heart disease.

Methods of collecting data: 120 CKD patients coming to MKCG medical college were studied with their consent. Patients were screened based on inclusion and exclusion criteria and selected patients were thoroughly examined. The evaluation comprises detailed history, physical examination and relevant investigations. A complete history was recorded with special emphasis to detect any clinical condition that predisposes to PH, comorbidities, and history of renal disease (etiology of renal failure, duration of HD therapy). Laboratory investigations like serum urea, creatinine, hemoglobin (Hb) level, LFT, sodium, potassium, FBS (fasting blood sugar), PPBS (postprandial blood sugar), HIV, HbSAg, HCV were done. Staging of CKD was done on the basis of GFR obtained by CKD-EPI formula. Digital chest X-Ray, ECG, 2D echocardiography were done for all patients.

Doppler echocardiography Two-dimensional and M-mode echocardiography were performed in all patients. Pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure 20 mmHg at rest, measured by right heart catheterisation and PASP  or equal to 35 mm of Hg. Though, right heart catheterization is gold standard for detection of pulmonary hypertension, it can also be deducted from tricuspid regurgitation velocity (TRV). Based on the pulmonary artery pressure, they were classified into three groups of mild degree(25-35mmHg), moderate (35-50 mm Hg) severe degree (50 mmHg). TRV was calculated from colour Doppler, echocardiography. elevated TRV 2.5  is significantly associated with pulmonary hypertension (William’s Haematology, 9^th Edn, P. 769). Following formulas were used to derive mean pulmonary artery pressure.

Statistical analysis: Results were analyzed and presented as frequency, percentage, mean and standard deviation. Chi square was used to find an association between variables.   value  0.05 was taken as statistically significant. Data entry was done using Microsoft Excel and analysis was carried out with the help of Statistical Package for Social Sciences (SPSS, Ver. 24).

In our study maximum number of patients were in more than 60 years of age i.e. 52 (43.3%) [Table 1]. Mean age was 58.8 years. Out of 120 patients 78 were male (65%) and 42 were female (35%). 40 male and 20 female in dialysis dependent group and 38 male and 22 female in non-dialysis dependent groups were included. In our study group total 41 patients had diabetes i.e. 34.2 % of study population [Table 2]. More number of patients i.e. 69 (57.5%) had systemic hypertension [Table 3] and of them 33(27.5%) had pulmonary hypertension [Table 4]. Out of 120 chronic kidney disease patients 60 patients were on HD (hemodialysis) and 60 on conservative treatment. Table 5 shows the mean eGFR was 17.68 with mean duration of dialysis 12.72 months ranging from 1 month to 36 months. Patients had mean Hb level of 8.69 gm/dl. The mean Hb was 7.53 gm% in dialysis group and 10.1gm% in non-dialysis group. Mean urea level in dialysis and non-dialysis group was 150 mg/dl and 80 mg/dl respectively. Mean creatinine level in dialysis and non-dialysis group was 7 and 2.4 mg/dl respectively. Total 62 patients were in end stage renal disease. 30.8% patients were in stage 4 and 17.5 % in stage 3 of CKD [Figure 1].

In our study we found the presence of LVH (left ventricular hypertrophy) in 43 (35.83%) of dialysis group and 20 (16.67%) of non-dialysis group of CKD patients. Out of 120 patients total 55 patients had pulmonary hypertension. Out of 60 non dialysis dependent patients 9 (7.5%) and in hemodialysis patients 46 (38.3%) had PH. In dialysis dependent patients 17 patients had mild PH (14.2%), 21 patients had moderate PH (17.5%) and 8 had severe PH (6.7%). In Patients with conservative management 9 had mild PH (7.5%). Out of 120 patients 55 had pulmonary hypertension. Among 55, 44 (80%) were from stage 5 and 20% from stage 4. The prevalence of PH in stage 5 was 36.6%. The mean age in patients with PH was 63.51 ± 11.16 years and range (SD) was 30-82 and without PH was 54.82 ± 10.38 years (range 28-80) and p value < 0.001 [Figure 2]. Mean Hb level in pulmonary hypertension patient was 7.36 gm/dl with range (SD) 5.50 - 9.60 and rest patients were 9.82gm/dl range 7.00-11.50 and p value <0.001. Mean Hb level in patients with mild PH was 7.75, moderate PH it was 6.97 and severe PH was 7.09 and p value <0.001[Figure 5].

Table -1: Age wise distribution of patients

Table-2: Prevalence of Pulmonary Hypertension in diabetes patients

Table-3: Frequency of HTN in dialysis and non- dialysis group

Table-4: Prevalence of PH in hypertensive study populations

Table -5: Renal status of study population

Table -6: Distribution of study participants in different stages of CKD

Table -7: Prevalence of PH in CKD patients with and without dialysis.

Table-8: Correlation of severity of PH with duration of dialysis

Figure 1: Prevalence of grading of PH in CKD patients

Figure 2: Relation of PH with increasing age

Figure 3: PH in male and female patients

Figure 4: Correlation of Hb with PH

Figure-5: Correlation of severity of PH with Hb level

Pulmonary hypertension (PH) is highly prevalent in end stage renal disease. Many studies have confirmed this. Some studies performed in US^11,12,13 showed prevalence of pulmonary hypertension ranged from 25-47%: values were more consistent (32-42%) in four studies that adopted cutoff values of. Also, the prevalence of pulmonary hypertension is lower in patients treated with peritoneal dialysis  than HD (. In a recent study it was shown that the incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6% ¹⁶. In a recent study, pulmonary artery hypertension had  prevalence in cohort of 228 HD patients and conveyed a high risk of death. The pathogenesis of PH in this population remains poorly understood. Reported associations include arteriovenous fistulae, cardiac dysfunction, fluid overload, bone mineral disorder, anemia and non-biocompatible dialysis membranes. Due to small numbers and cross-sectional nature of majority of studies no consistent association with any particular risk factor has been demonstrated. Further, little is known about impact of ‘uraemic vasculopathy’ on pulmonary vasculature. Hence there is a need for better understanding of natural history and the pathogenesis of the condition which would help to individualise treatment of PH in end stage renal disease. In this study, an attempt was made to study the prevalence of pulmonary hypertension and correlation between different clinical and metabolic parameters with prevalence of pulmonary hypertension among CKD patients both dialysis (hemodialysis) and non-dialysis dependent attending MKCG medical college and hospital.

In our study, there were total of 120 CKD patients, which included 60 patients on conservative management (non-dialysis) and 60 patients were dialysis dependent. Among 60 dialysis patients, all were on hemodialysis. Patients undergoing hemodialyis had access through arteriovenous fistula . The mean age of patients in the dialysis group was found to be 63.51 years, and was 60.8 years in the study done by Farid Net al¹⁷. In the non-dialysis group, it was 54.82 years. In this study we found that more prevalence of pulmonary hypertension in patients with age >60 years of age. It may be due to the increased duration of CKD in these age group patients. In my study, there were 40 males and 20 females in dialysis and 38 males and 22 females in non-dialysis dependent groups. There is no significant difference in prevalence of pulmonary hypertension in gender (p>0.05).

Considering the etiology of CKD in our patients, it was found that 34.2 % of patients had diabetes mellitus and 57.5% had hypertension as the cause which is comparable to the study done by 18. Alhamad EH et al where he found that both these factors contributed to 65% as an etiology for. It is because diabetes and hypertension being the leading cause of diabetes in world.

Among the dialysis dependent patients those were included in the study, the minimum and maximum duration of dialysis was 1 and 36 months respectively with mean of 12.72 months and standard deviation, and whereas in the study done by P. Patel etal the minimum duration was 10 months and maximum duration was 50 months¹⁹.

The mean hemoglobin level among the 120 CKD patients was 8.69 gm%, this is lower to the observations in the study done by GK Modi et al²⁰ and P. Patel et al which was below and  respectively. We found that patients with PH, the mean Hb level was 7.36 gm% and patients without PH are. Also, the mean Hb level in dialysis group was where as in non-dialysis group it was 10.1gm%. It shows anemia can be a precipitating factor for pulmonary hypertension in CKD patients mostly in dialysis group of patients. It causes fluid overload and precipitate Left ventricular dysfunction, which are the probable mechanism of development of pulmonary hypertension.

2D Echocardiogram was done in all 120 CKD patients,  patients had pulmonary hypertension of varying degrees. Further, among patients who had PH  were dialysis dependent (hemodialysis) which was statistically significant (p<0.001). This is comparable to the study done by P.Patel et of patients on HD with AV fistula had PH as shown in the study done by Mordechai Yet al²¹. 49.3% of patients receiving HD had pulmonary hypertension as evidenced in the study done by Seyed Aet al²². Pulmonary hypertension was found in 30.6% of patients on hemodialysis as shown in the study done by Hugo Het  of patients had PH undergoing HD as seen in cross sectional study done by Fabbian Fet al.

A high prevalence of pulmonary hypertension i.e 48.7% with dialysis vs non- dialysis being was found in study done by Nithiya N et al According to an update given by William Hopkins and Thomas A Gopler prevalence of pulmonary hypertension in ESRD patients was 9-39%, patient on hemodialysis was  and on peritoneal dialysis was 13-19%²⁶. A high prevalence of pulmonary hypertension was demonstrated among 41.53% patients receiving hemodialysis as shown in study done by Magdy M et al.

Out of  patients 21 were on stage  were on stage 4 and rests 62 were on stage 5. Out of  patients who had pulmonary hypertension  were from stage from stage 4. This is similar to the study done by Javier Reque et al ²⁸ which showed that the prevalence of pulmonary hypertension in stage was respectively. There is significant increase in prevalence of pulmonary hypertension among stage 5 CKD patients. This significant increase may be contributed to the presence of AV Fistula, LV volume overload which can lead to increase in cardiac output and increase in pulmonary artery pressure. Severity of pulmonary hypertension among the dialysis dependent group were classified into three, that comprised of patients having mild pulmonary hypertension, moderate and of them had severe pulmonary hypertension. In my study, it was also found that the mean duration of dialysis in months is directly proportional to the severity of pulmonary hypertension. Mean value serum creatinine among patients with PH was  and patients without PH were. As the stage of CKD worsens increase in s.creatinine (p<0.001) and had significant correlation with prevalence of pulmonary hypertension. All the patients undergoing hemodialysis those were included in my study had AVF access and low hemoglobin levels, which probably could be the reason for high prevalence of PH among these patients; along with other factors like lower hematocrit, serum bicarbonate and higher serum creatinine levels, which is also seen in the study done by Farid N et al

Cardiovascular complications are more common in patients with CKD and certain complications gets aggravated when they are subjected to long term dialysis. Among those complications, pulmonary hypertension is of more importance. We found that prevalence of pulmonary hypertension is more common among patients on dialysis rather than those on conservative management. Hemodialysis patients had high prevalence of PH, owing to their AVFs and other factors. Also, the prevalence linearly increases with the duration of hemodialysis. So this complication should be anticipated early in the course of the disease and should be addressed early. Because the long term prognosis and mortality in these patients are directly proportional to the severity of pulmonary hypertension. So do we need to switch to alternate mode of dialysis, like PD should be thought upon; but again its efficacy as compared to hemodialysis is low.

Conflict of interest: Nil

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