Pulmonary hypertension (PH) is a complex hemodynamic alteration that can have several underlying causes. The 2008 WHO classification and the more current guidelines from the European Society of Cardiology (ESC) included PH in dialysis patients for the first time. The illness was classified as belonging to the fifth group, a limbo category that encompasses a range of PH types "with unclear or multifactorial aetiology." At the time, there was only one survey available to dialysis patients, and the findings showed an atypically high frequency of PH. This high prevalence was mostly due to left ventricular (LV) issues and hypertrophic cardiac output caused by fluid overload, arterio-venous fistula anemia, or both.[1,2,3]

Post-hypertension (PH) in patients with renal diseases has garnered increasing attention in the last five years. Consequently, more than 100 original or review papers that discuss pre-dialysis chronic kidney disease (CKD), transplant patients, and PH in dialysis patients have been deposited in PubMed. Chronic kidney disease (CKD) is a global public health concern due to its prevalence and high treatment costs. The severity may have been exaggerated because individuals with chronic kidney disease (CKD) had a higher risk of dying from cardiovascular diseases (CVD) than from end-stage renal disease (ESRD).[4] The main causes of chronic kidney disease (CKD) in India are chronic glomerulonephritis (15.8%), hypertension (14.8%), and diabetic nephropathy (30.3%), according to data from the Indian Registry. About 30% of people with diabetes mellitus (DM) also have diabetic nephropathy, and as the population ages and the number of DM patients increases, so too is the incidence of chronic kidney disease (CKD).[5]

Numerous comorbidities arise in CKD patients at any stage of the disease's development. Renal function can only be partially restored by maintenance dialysis. Six Of the three treatment methods currently available, haemodialysis (HD), peritoneal dialysis, and kidney transplantation, is used for the majority of patients. The relationship between HD and pulmonary hypertension (PH) has recently been established. "A mean pulmonary artery pressure more than or equal to 25 mmHg at rest or 30 mmHg during exercise" is how PH is defined. The precise path of PH development in CKD is unknown.[6]

Pulmonary hypertension (PHT) is a diverse group of conditions that deteriorate health-related quality of life and have unfavourable outcomes if left untreated. In circumstances where there is clinical suspicion, transthoracic echocardiography (TTE) can be helpful, but right heart catheterization remains the gold standard diagnostic method. In the 6th World Symposium on PHT, it was proposed that the definition of PHT be defined as having a mean pulmonary artery pressure of more than 20 mmHg at rest.[7]

It is believed to be the outcome of multiple changed elements related to cardiovascular physiology working together. Myocardial dysfunction, which raises left ventricular filling pressure and causes pulmonary venous hypertension, is the most frequent cause of PH in chronic kidney disease. Eleven Additional factors involved include increased cardiac output (CO), shunting across an arteriovenous fistula (AVF) that results in increased pulmonary blood flow, volume overload, anemia, exposure to dialysis membranes, and endothelial dysfunction that causes pulmonary vasoconstriction, decreased pulmonary vasculature compliance, vascular stiffening and calcification, elevated thromboxane B2, and pro-brain natriuretic peptide.

Pulmonary hypertension is classified into five clinical groups: Pulmonary arterial hypertension (PHT) is the first group; left heart disease is the second group; lung illnesses and/or hypoxia are the third group; chronic thromboembolic pulmonary hypertension (CTEPH) is the fourth group; and PHT with unclear causes and/or multifactorial is the fifth group. Thirteen Moreover, individuals with PHT comprise Group 5, who may also be associated with metabolic problems, sickle cell disease, myeloproliferative disorders, sarcoidosis, and chronic kidney disease (CKD).[8]

There is no known true incidence of PHT in individuals with chronic kidney disease (CKD), and the epidemiology of the condition has only been largely described in the few published studies. For instance, in one study, 1876 individuals with CKD (stages 1 through 5) were diagnosed using right cardiac catheterization. According to reports, the prevalence of PHT was 68%, with stage 5 CKD having the highest percentage. PH in CKD patients is a good predictor of increased mortality.

Pulmonary hypertension (PH) is an often-overlooked cardiovascular complication of chronic kidney disease (CKD), particularly in end-stage renal disease (ESRD). The prevalence of PH in ESRD patients ranges from 27% to 58%. Compared to patients with end-stage renal disease (ESRD), the prevalence of PH in people with severe chronic kidney disease (CKD) ranges from 8% to 39%. Most patients with chronic kidney disease (CKD) have several characteristics that might lead to increased pulmonary vascular pressures. These disorders include diastolic dysfunction in hypertension, arteriovenous fistulas (AVF), anemia, uremic lung, volume overload with interstitial pulmonary edoema, and a high cardiac output state. Uremic endothelial dysfunctions also contribute to PH by disrupting the equilibrium between vasodilators (such as nitric oxide and endothelin 1) and vasoconstrictors (such as thromboxane, plasma asymmetric dimethylarginine, and prostacyclins).[9]

Extraosseous vascular calcification and recurrent pulmonary thromboembolic illness (due to microbubbles from HD tubing or dialyzers and vascular access thrombectomy) are two more theories that have been put forth. In ESRD, PH is associated with higher death rates. According to an observational study, patients receiving hemodialysis who had PH had a death rate of 30.4%, compared to 8.5% for those who did not. Certain factors such as prostacyclin analogues and endothelin receptor antagonists may be considered under carefully selected conditions.[2]

Research has looked at the connection between PHT and overvolemia, inflammation, malnutrition, and electrolyte overload. Nevertheless, it is still unknown whether precise pathways and risk factors lead to PHT in individuals with end-stage renal disease (ESRD). The incidence and prevalence of PH in patients with chronic kidney disease (CKD) in India are little studied. Here, we focus on the clinical epidemiology of PH in patients with CKD at our tertiary care center along with relationship between the prevalence of PH and CKD

The study was conducted among patients attending Department of General Medicine of Malla Reddy Narayana Multispeciality Hospital, Hyderabad from September 2022 to January 2024 , 100 Subjects presenting with or diagnosed with chronic kidney disease.

Inclusion criteria : Age > 18 years in patients with GFR <30ml/min per 1.73M2

Exclusion Criteria: Subjects below 18 years, Patients who have ejection fraction less than 45%, who are known case of thrombo- embolic disease, sarcoidosis, sickle cell disease, connective tissue disorder and congenital heart disease

Patients who satisfied the inclusion criteria and who gave written informed consent were included in the study.

All patients seen during the study period were screened to determine eligibility for inclusion in the study. A Study proforma was used to collect the patients details and findings. History was taken from patients and attenders. Important history regarding symptoms was taken. The subjects are identified with a chest radiograph and a standard 12- lead ECG.

Lab investigations done as serum creatinine, urea, haemoglobin, serum calcium, serum phosphorus, alkaline phosphatase, doppler echocardiography and ultrasound Abdomen

Statistical analysis

The data collected was coded, entered into Microsoft excel work sheet and exported to SPSS. Data was analysed using statistical package for social sciences (SPSS) version 26. Data is presented as percentages, means and standard deviations represented by tables, charts and histograms. Independent t test and Chi Square was used for test of significance. A p- value of 0.05 was considered statistically significant for all statistical tests performed.

Table 1: Distribution according to demographic details

Age distribution among the subjects were 38% were between 41 and 50 years, 27% were between 51- 60 years, 20% were between 31 to 40 years and 15% were above 60 years. The mean age in the study was 49.4± 9.4 years. The study consisted of 69 males and 31 females with the sex ratio being 2.2: 1 [M: F]. In the study among the 100 subjects 31% had diabetes, 22% had hypertension and 43% had diabetes and hypertension together.

Table-2: Duration of Dialysis and CKD staging

The duration of CKD was noted for all the subjects were 38% the duration was one and two years, 17% the duration was 3 years, 15% the duration was 4 years, 24% the duration was 5 years and 6% the duration was <6 months. It was noted for all the subjects were 48% were stage 5 and 52% were stage 4.

Table-3: Investigations done in patients

It was observed in the study all the subjects had elevated levels of serum creatinine, serum calcium, serum phosphorus, decreased serum albumin in 21% and 83% had haemoglobin <12 g/dl. The mean levels were 5.2± 3.9 mg/dl, 8.9± 0.7 (mEq/L), 2.7± 0.6 (mmol/L), 3.7± 0.4 (g/dL) and 10.4± 1.7 (g/dL) for creatinine, calcium, phosphorus, albumin and haemoglobin respectively.

Table-4: Distribution of pulmonary artery hypertension and staging of PAH

The prevalence of pulmonary artery hypertension among the 100 chronic kidney disease subjects in the study was 15%. Among the 15 patients with pulmonary artery hypertension 11 (73.3%) were stage 5 CKD and 4 (26.7%) were stage 4.

Table-5: Association between other factors and pulmonary artery hypertension

Association between various risk factors and development of pulmonary artery hypertension among chronic kidney disease patients. In the study it was observed middle age (50 years), males, increased duration of CKD, stage 4 & 5, increasing creatinine, increasing calcium, increasing phosphorus, decreased albumin and decreasing haemoglobin were highly statistically significantly associated with pulmonary artery hypertension (p<0.001).

 In the present study, 38% were between 41 and 50 years, 27% were between 51- 60 years, 20% were between 31 to 40 years and 15% were above 60 years. The mean age of the study population was 49.4± 9.4 years. Around 69% were males and 31% were females and the sex ratio was 2.2: 1 [M: F]. The present study findings concurred with a study by Li Z et al[10] in which mean age was 52.5 ±18 years. The present study findings were similar with a study by Zhang Q et al[11]  in which mean age of study subjects was 48.9± 16.7 years. Around 57.1% were males and 42.9% were females. The present study findings were in contrast with a study by Zhang Y et al[12] in which mean age of study subjects was 52.9 ± 14.2 years. Sohan B et al[13] reported mean age of study subjects as 51.9± 12.6 years and higher proportion of males (73.5%) as compared to females (26.5%).

The present study findings were consistent with a study by Suresh H et al[14]  in which mean age of study population was 43.5± 14.6 years and sex ratio of M:F was 2.7:1. The present study findings were similar to a study by Javeria S et al[15]  in which mean age of study subjects was 48.6 years and 76% were males. In this study, 31% had diabetes, 22% had hypertension and 43% had both diabetes and hypertension as comorbidities. The % are high due to small sample size. The present study findings concurred with a study by Li Z et al[10] in which 19.2% had hypertension and 18.2% had diabetes. The present study findings were different with a study by Zhang Q et al[11] in which 14.7% had diabetes and 8% had hypertension. Sohan B et al[13] reported associated Co-morbidities with CKD as anemia (70.59%), diabetes mellitus (57.35%), systolic hypertension (32.35%) and diastolic hypertension (26.47%). The present study findings were similar to a study by Javeria S et al[15]  in which 43.8% were diabetics and 66.3% were hypertensives.

The present study findings concurred with a study by Mehta KS et al[16] in which 44.6% had diabetes, 24.7% had Hypertension. In the present study, the duration of CKD was found to be 1 – 2 years in 38%, 3 years in 17%, 4 years in 15% and 5 years in 24%. Around 6% had the duration of <6 months. The present study findings were similar to a study by Sohan B et al[13] in which mean duration of CKD was 43.11 + 26.78 weeks. The present study findings concurred with a study by Mehta KS et al[16] in which 12% had duration of CKD <6 months, 56.5% had duration of 6 – 12 months and 31.5% had duration of > 1 year. In this study, 73.3% had stage 5 CKD and 26.7% had stage 4 CKD. All the subjects had advanced stages of CKD and none of them had early stages (Stage 1 and Stage 2).

The present study findings were similar to a study by Sohan B et al[13] in which majority (69.12%) of patients had stage 4 CKD and 30.88% had stage 5 CKD. The present study findings were similar to a study by Atul M et al[17] in which 50% were Stage 4 CKD patients and 50% were stage 5 CKD patients. It was observed in the present study that all the subjects had elevated levels of serum creatinine, serum calcium, serum phosphorus. The mean Serum creatinine levels were 5.2± 3.9 mg/dl, mean calcium levels were 8.9± 0.7 (mEq/L) and mean phosphorus levels were 2.7± 0.6 (mmol/L). Around 21% subjects gad decreased albumin levels (<3.4 g/dL) and mean albumin levels were 3.7± 0.4 (g/dL). Around 83% subjects had hemoglobin levels <12 g/dL and mean hemoglobin levels were 10.4± 1.7 (g/dL). The present study findings concurred with a study by Mehta KS et al[16] in which 56.5% had anemia, 41.5% had raised serum creatinine, 9% had raised serum calcium and phosphorus.

In this study, the prevalence of pulmonary artery hypertension among chronic kidney disease patients was 15%. The present study findings concurred with a study by Li Z et al[10] in which prevalence of pulmonary hypertension among CKD patients was 18.1%. The present study findings were different with a study by Zhang Q et al[11] in which 47.38% of CKD patients were found to have Pulmonary hypertension. The present study findings were in contrast with a study by Zhang Y et al[12] in which incidence of PH among ESRD patients was 34.6%. Sohan B et al[13] reported an incidence of 51.3% of pulmonary hypertension among CKD patients. The present study findings were different with a study by Suresh H et al[14] in which prevalence of pH was 50% among CKD patients. The present study findings were similar to a study by Javeria S et al[15] in which PAH was found in 18.75% of CKD patients. The present study findings differed with a study by Mehta KS et al[16]  in which the prevalence of PH in CKD patients was as high as 60.5%. Atul M et al[17]  found prevalence of PAH as 61% among CKD patients which was comparatively very higher value as compared to the present study.

The present study findings were similar to a study by Kumari N et al[18]  in which prevalence of Pulmonary artery hypertension among CKD patients was 16%. The present study findings were almost comparable with a study by Yang QM et al[19] in which prevalence of pulmonary arterial hypertension was 23.76%. The present study findings were different to a study by Sise ME et al[20] in which prevalence of PH among CKD patients was ranging from 30 – 50%. The present study findings were different with a study by Magdy ME et al[21] in which prevalence of PAH was very high (41.53%). The present study findings were consistent with a study by Navaneethan SD et al²² in which prevalence of PAH among CKD patients was 21%.

In the present study, it was observed middle age (50 years), males, increased duration of CKD, stage 4 & 5, raised creatinine, raised calcium, raised phosphorus, decreased albumin and reduced haemoglobin levels were significantly associated with pulmonary artery hypertension (p<0.001). The present study findings concurred with a study by Li Z et al[10] in which advanced stages of CKD (stage 5) were found to be associated with PAH. The present study findings were similar with a study by Zhang Q et al[11]  in which stage 4 and 5 of CKD, patients on dialysis, reduced haemoglobin levels and proteinuria were found to be risk factors for PAH in CKD patients. The present study findings were similar to a study by Sohan B et al[13] in which Diabetes and hypertension were reported to be significantly associated with PAH.

The present study findings were consistent with a study by Suresh H et al[14]  in which progression of CKD stage, reduced mean haemoglobin levels, and impaired calcium and phosphate levels were significantly associated with PH among CKD patients. The present study findings concurred with a study by Mehta KS et al[16] in which PAH was associated with advanced CKD stage, diabetes and hypertension. The severity was found to significantly increase with duration of CKD and duration of hemodialysis. Serum creatinine and serum calcium-phosphorus levels were significantly higher in patients with PH. There was negative correlation between hemoglobin and pulmonary hypertension. Atul M et al[17] concluded that there was significant association between PAH and systolic hypertension, haemodialysis, arteriovenous fistula (AVF), CKD severity & haemodialysis duration. Anaemia, low calcium and high phosphate, were significantly associated with PAH. The present study findings were similar to a study by Kumari N et al[18] in which PAH was significantly associated with stage 5 CKD patients. The present study findings slightly differed with a study by Yang QM et al[19] in which early stage (1- 3) of CKD had pulmonary hypertension.

The present study findings were consistent with a study by Magdy ME et al[21] in which older age, ESRD, longer duration of dialysis treatment and AV fistula were found to be associated with PAH. The present study findings were consistent with a study by Navaneethan SD et al[22] in which advanced stages of CKD, anaemia, older age had greater odds for PH. The present study findings were similar to a study by Bolignano D et al[23] in which PH in CKD patients was found to be aggravated among patients on hemodialysis, arteriovenous fistula and severe anemia. The present study findings concurred with a study by Stallworthy EJ et al[24] in which advancing age, diabetes, severe stages of CKD were found to be associated with PH. The present study findings were similar to a study by Gauswami BS et al[25] in which there was positive correlation between PH and duration of CKD, stage of CKD and duration of hemodialysis..

The implications of these findings are substantial. PAH in CKD patients is associated with poorer functional capacity, increased cardiovascular morbidity, and reduced survival. Therefore, early identification of high-risk individuals is essential. Routine screening using echocardiography, careful monitoring of biochemical abnormalities, and timely correction of modifiable factors may help delay or prevent the progression of PAH. Furthermore, optimizing dialysis adequacy, managing anemia, improving nutritional status, and addressing mineral bone disorder may collectively improve patient outcomes.

In conclusion, pulmonary arterial hypertension represents an important and often under-recognized complication of chronic kidney disease. A comprehensive and multidisciplinary approach is crucial for early detection, appropriate management, and prevention of further deterioration. Future studies with larger sample sizes and longitudinal follow-up are recommended to better understand causal pathways and to develop targeted therapeutic strategies for this vulnerable population.

Limitation

1. Small sample size
   2. There could be an element of information bias in this study.
   3. Limited previously conducted studies especially in Indian population.

Recommendations

To identify, diagnose and reduced the incidence of PAH via regular screening patients especially with comorbidities.

1. Identification of risk factors.
2. Reduce complications

Early intervention is required to minimize morbidity and mortality.

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