Pulmonary hypertension (PH) is now recognised as a frequent and prognostically adverse complication of chronic kidney disease (CKD), reported in between 8% and 40% of patients depending on disease stage and diagnostic method [1,2]. Its presence independently predicts mortality and cardiovascular events across both non-dialysis CKD and end-stage renal disease populations [3,4], and complicates candidacy for renal transplantation [5]. In the current classification framework, PH arising in the setting of renal failure is assigned to the group of conditions with unclear or multifactorial mechanisms [6], an assignment that reflects genuine uncertainty rather than a settled understanding. Several distinct pathways have been proposed. The first is anaemia. Erythropoietin deficiency renders anaemia near-universal in advanced CKD [7], and the resulting reduction in oxygen-carrying capacity is compensated by a sustained rise in cardiac output. Chronically elevated pulmonary blood flow, superimposed on a pulmonary vascular bed already stiffened by uraemia, raises pulmonary artery pressure even in the absence of any increase in vascular resistance. The second is disordered mineral metabolism. Declining renal phosphate excretion produces hyperphosphataemia and, through reduced calcitriol synthesis and secondary hyperparathyroidism, hypocalcaemia [8]. Elevated calcium–phosphate product drives medial vascular calcification, and Block et al. established a direct association between serum phosphorus and mortality in haemodialysis patients [9]. Calcification of the pulmonary arterial tree would be expected to reduce compliance and elevate pulmonary vascular resistance, providing a plausible mechanistic bridge between mineral bone disorder and PH. The third is the haemodynamic burden of vascular access. A surgically created arteriovenous fistula generates an obligatory left-to-right shunt that increases venous return, cardiac output and pulmonary blood flow. Where fistula flow is high, this may be sufficient to elevate pulmonary artery pressure independently of any pulmonary vascular abnormality, and access-related PH has been described as a potentially reversible entity. The fourth is maintenance haemodialysis itself. Yigla et al. reported a high prevalence of PH among dialysis patients, and attributed it in part to the repeated cycles of interdialytic volume overload and rapid intradialytic fluid removal that characterise the treatment [10]. Whether haemodialysis contributes independently, or merely marks the most advanced disease, has not been settled; Pabst and colleagues found substantial PH burden in both dialysis and non-dialysis CKD [11]. Distinguishing among these mechanisms has direct therapeutic relevance, since each implies a different intervention — erythropoiesis-stimulating agents and iron for anaemia, phosphate binders and dietary restriction for mineral disorder, flow reduction or alternative access for fistula-related PH, and revised ultrafiltration targets for dialysis-related volume shifts. Yet published data correlating PH with biochemical parameters in CKD remain limited, and Indian cohorts — in whom anaemia is typically more severe and mineral bone disorder less aggressively managed than in Western practice — are particularly under-represented [12]. Notably, azotaemic markers such as serum creatinine and blood urea, though they define CKD stage, may not track PH at all if the operative mechanisms are haematological and mineral rather than uraemic [13]. The present study was therefore designed to compare the biochemical profiles of CKD patients with and without PH, and to examine the contribution of arteriovenous fistula and haemodialysis.

A prospective descriptive study was conducted in the Departments of Nephrology and General Medicine at Ballari Medical College and Research Centre (formerly Vijayanagar Institute of Medical Sciences), Ballari, Karnataka. Participants were recruited from both inpatient and outpatient services over a period of 18 months. Ethical considerations: Institutional review board approval was obtained before the study commenced, and written informed consent was taken from every participant prior to enrolment. Inclusion criteria: Patients with chronic kidney disease of any aetiology and of any age group were eligible if the estimated glomerular filtration rate was below 60 mL/min/1.73 m². Both conservatively managed patients and those established on maintenance haemodialysis were included. Exclusion criteria: Patients were excluded if pulmonary hypertension could plausibly be attributed to a non-renal cause. Specific exclusions were chronic obstructive pulmonary disease, parenchymal lung disease, chest wall disease, previously diagnosed pulmonary hypertension, previous pulmonary embolism, a smoking history exceeding five pack-years, and collagen vascular disease. Patients with a left ventricular ejection fraction below 50% or significant mitral or aortic valve disease were also excluded, so that post-capillary pulmonary hypertension due to overt left heart disease would not confound the comparison. Sample size estimation: Sample size was derived from the single-proportion formula n = (Z² × P × (1 − P)) / d², taking Z as 1.96 for 95% confidence, P as an assumed pulmonary hypertension prevalence of 0.605 from a previous study, and d as an absolute precision of 0.12. This yielded a minimum requirement of 64 participants, which was the number enrolled. Sampling: Simple random sampling was used to select participants from the eligible CKD population, and enrolment continued until the calculated sample size was reached. Biochemical assessment: Data were recorded on a structured proforma. For each participant, biochemical values were taken as the average of the last six available readings, a strategy adopted to minimise the influence of short-term fluctuation and, in dialysis patients, of the interdialytic cycle. The parameters analysed were haemoglobin, serum creatinine, blood urea, serum albumin, serum calcium and serum phosphorus. Vascular access status was recorded as the presence or absence of a functioning arteriovenous fistula, and dialysis status as maintenance haemodialysis versus conservative management. Cardiovascular assessment: All participants underwent twelve-lead electrocardiography, postero-anterior chest radiography and transthoracic echocardiography. Systolic pulmonary artery pressure was estimated from the peak tricuspid regurgitant velocity together with an estimate of right atrial pressure; right ventricular size and function, left ventricular ejection fraction and valve morphology were also assessed. Patients were classified into two groups on echocardiographic criteria — pulmonary hypertension present or absent — and these groups formed the basis of all comparisons. Statistical analysis: Data were entered into Microsoft Excel and analysed using SPSS version 24.0 (IBM, USA). Quantitative variables were summarised as mean ± standard deviation and qualitative variables as frequencies and proportions. Comparison of mean biochemical values between the pulmonary hypertension and non-pulmonary hypertension groups was performed using the unpaired t-test, with the t statistic and corresponding p value reported for each parameter. Associations between categorical variables, including arteriovenous fistula status and haemodialysis status against the presence of pulmonary hypertension, were tested using the chi-square test or Fisher's exact test where expected cell counts were small. A p value below 0.05 was considered statistically significant and a value below 0.001 highly significant.

Sixty-four patients with chronic kidney disease were studied, of whom 17 (26.6%) had echocardiographic pulmonary hypertension. Table 1. Baseline characteristics of the cohort (n = 64) Characteristic Value Male, n (%) 41 (64.1) Female, n (%) 23 (35.9) Aged 41–60 years, n (%) 34 (53.2) Systemic hypertension, n (%) 53 (82.8) Diabetes mellitus, n (%) 22 (34.4) CKD stage 4 or 5, n (%) 54 (84.4) On maintenance haemodialysis, n (%) 41 (64.1) Arteriovenous fistula present, n (%) 24 (37.5) Pulmonary hypertension present, n (%) 17 (26.6) The cohort comprised predominantly middle-aged men with advanced renal failure: 54 patients (84.4%) were in CKD stage 4 or 5 and 41 (64.1%) were established on maintenance haemodialysis. An arteriovenous fistula had been created in 24 patients (37.5%). Pulmonary hypertension was present in 17 patients (26.6%), giving group sizes of 17 with and 47 without for all subsequent comparisons. Table 2. Pulmonary hypertension in relation to arteriovenous fistula (n = 64) Arteriovenous fistula Total (n) PH present (n) PH absent (n) Prevalence within group (%) p value Present 24 11 13 45.8 0.01* Absent 40 6 34 15.0 Total 64 17 47 26.6 *Statistically significant. The presence of an arteriovenous fistula was significantly associated with pulmonary hypertension. Among the 24 patients with a fistula, 11 (45.8%) had pulmonary hypertension, compared with only 6 of 40 (15.0%) without one — a threefold difference reaching statistical significance (p = 0.01). A related but distinct figure warrants clarification: 11 of the 17 patients with pulmonary hypertension (64.7%) had a fistula, which describes the composition of the affected group rather than the risk conferred by a fistula. The clinically meaningful quantity is the 45.8% prevalence among fistula-bearing patients. This finding is consistent with the shunt physiology of arteriovenous access, in which augmented venous return and cardiac output raise pulmonary blood flow. Table 3. Pulmonary hypertension in relation to maintenance haemodialysis (n = 64) Haemodialysis Total (n) PH present (n) PH absent (n) Prevalence within group (%) p value Yes 41 14 27 34.1 0.07 No 23 3 20 13.0 Total 64 17 47 26.6 Pulmonary hypertension was more than twice as common among patients on maintenance haemodialysis (14 of 41, 34.1%) as among those managed conservatively (3 of 23, 13.0%), but this difference fell just short of conventional statistical significance (p = 0.07), reflecting limited power at this sample size. As with the fistula analysis, the widely quoted figure of 82.4% refers to the proportion of pulmonary hypertension cases who were on dialysis (14 of 17), not to the prevalence among dialysis patients, which was 34.1%. Since dialysis status, fistula presence and advanced CKD stage are closely interdependent, the independent contribution of haemodialysis itself cannot be isolated in an analysis of this size. Table 4. Comparison of biochemical parameters between patients with and without pulmonary hypertension Parameter PH present (n = 17) Mean ± SD PH absent (n = 47) Mean ± SD t statistic p value Inference Haemoglobin (g/dL) 8.38 ± 1.27 9.84 ± 1.92 2.888 0.005 Significant Serum creatinine (mg/dL) 6.84 ± 3.83 5.40 ± 3.15 −1.521 0.133 Not significant Blood urea (mg/dL) 115.12 ± 40.08 103.76 ± 60.66 −0.716 0.477 Not significant Serum albumin (g/dL) 2.66 ± 0.35 2.88 ± 0.39 1.973 0.053 Not significant Serum calcium (mg/dL) 7.88 ± 0.77 9.25 ± 0.73 6.504 0.0001 Highly significant Serum phosphorus (mg/dL) 3.49 ± 0.45 2.87 ± 0.41 −5.242 0.0001 Highly significant This table constitutes the principal analysis. Three parameters differed significantly between groups. Haemoglobin was 1.46 g/dL lower in patients with pulmonary hypertension (8.38 versus 9.84 g/dL, p = 0.005), a difference of clinical as well as statistical importance given that anaemia of this severity sustains a compensatory high-output state. Serum calcium was 1.37 mg/dL lower (7.88 versus 9.25 mg/dL) and serum phosphorus 0.62 mg/dL higher (3.49 versus 2.87 mg/dL), both at p = 0.0001, indicating that patients with pulmonary hypertension carried a markedly more deranged mineral profile. The t statistic for calcium (6.504) was the largest in the analysis, making it the strongest single discriminator between the two groups. By contrast, serum creatinine and blood urea, though numerically higher in the pulmonary hypertension group, did not differ significantly (p = 0.133 and 0.477). Serum albumin was marginally lower at 2.66 versus 2.88 g/dL, narrowly missing significance at p = 0.053. Table 5. Biochemical parameters ranked by strength of association with pulmonary hypertension Rank Parameter Direction in PH group t statistic (absolute) p value Significance 1 Serum calcium Lower 6.504 0.0001 Highly significant 2 Serum phosphorus Higher 5.242 0.0001 Highly significant 3 Haemoglobin Lower 2.888 0.005 Significant 4 Serum albumin Lower 1.973 0.053 Borderline 5 Serum creatinine Higher 1.521 0.133 Not significant 6 Blood urea Higher 0.716 0.477 Not significant Ranking by the magnitude of the t statistic clarifies the pattern. The two mineral metabolism parameters occupy the top two positions by a wide margin, followed by haemoglobin. Albumin sits at the threshold of significance, suggesting a real but weaker association possibly mediated through the malnutrition–inflammation complex. The two azotaemic markers rank last and are clearly non-significant. This ordering carries a mechanistic implication: pulmonary hypertension in CKD appears to track with the metabolic and haematological consequences of renal failure rather than with the degree of nitrogenous waste retention. Table 6. Consolidated summary of factors associated with pulmonary hypertension Factor Comparison Prevalence or mean difference p value Association Serum calcium PH versus no PH −1.37 mg/dL 0.0001 Highly significant Serum phosphorus PH versus no PH +0.62 mg/dL 0.0001 Highly significant Haemoglobin PH versus no PH −1.46 g/dL 0.005 Significant Arteriovenous fistula Present versus absent 45.8% versus 15.0% 0.01 Significant Maintenance haemodialysis Yes versus no 34.1% versus 13.0% 0.07 Trend only Serum albumin PH versus no PH −0.22 g/dL 0.053 Borderline Serum creatinine PH versus no PH +1.44 mg/dL 0.133 Not significant Blood urea PH versus no PH +11.36 mg/dL 0.477 Not significant Bringing the biochemical and access-related findings together, four factors were significantly associated with pulmonary hypertension: hypocalcaemia, hyperphosphataemia, anaemia and the presence of an arteriovenous fistula. Haemodialysis showed a consistent but non-significant trend. All four significant factors are amenable to intervention — through phosphate binders and vitamin D analogues, erythropoiesis-stimulating agents and iron, and consideration of access flow — which gives the pattern practical as well as mechanistic interest.

The prevalence of pulmonary hypertension in this cohort was 26.6%, comparable with the 30% reported by Yigla et al. in end-stage renal disease [10] and consistent with the wider literature [1,2,11]. The value of the present analysis lies less in this figure than in the pattern of factors associated with it. Haemoglobin was significantly lower in patients with pulmonary hypertension (8.38 versus 9.84 g/dL, p = 0.005). Stauffer and Fan documented the high prevalence of anaemia in CKD and its association with cardiovascular risk [7], and the mechanism is well described: reduced oxygen-carrying capacity sustains a compensatory rise in cardiac output, which in a pulmonary bed already stiffened by uraemia elevates pulmonary artery pressure without any necessary increase in resistance. This supports a therapeutic role for erythropoiesis-stimulating agents and iron repletion, though the observational design cannot establish that correcting anaemia lowers pulmonary pressure. The mineral findings were the strongest in the analysis. Serum calcium was markedly lower and phosphorus higher in the pulmonary hypertension group, both at p = 0.0001. Levin et al. described the frequency of these derangements across the CKD spectrum [8], and Block et al. established a direct relationship between serum phosphorus and mortality in haemodialysis patients [9]. Hyperphosphataemia promotes osteogenic transformation of vascular smooth muscle and medial calcification; extension of this process to the pulmonary arterial tree would reduce compliance and raise resistance. That calcium generated the largest t statistic in the study (6.504) suggests mineral bone disorder is at least as important as anaemia in this population. Serum creatinine and blood urea were numerically higher in the pulmonary hypertension group but not significantly so (p = 0.133 and 0.477). This negative finding is informative rather than merely null: it indicates that pulmonary hypertension does not simply mirror the degree of azotaemia, and aligns with the observation that markers of filtration and pulmonary pressure are only loosely coupled [8]. Serum albumin was borderline lower (p = 0.053), consistent with the association Kaysen et al. described between hypoalbuminaemia, inflammation and adverse outcome in dialysis patients [14]. The significant association with arteriovenous fistula (45.8% versus 15.0%, p = 0.01) accords with the shunt hypothesis, in which increased venous return and cardiac output raise pulmonary blood flow. Haemodialysis showed a parallel but non-significant trend (34.1% versus 13.0%, p = 0.07), in keeping with the association reported by Yigla et al. [10] and attributable to cyclical volume overload and rapid ultrafiltration. Limitations: The single-centre sample of 64 with only 17 affected patients limits power, and the design is effectively cross-sectional, precluding causal inference. Diagnosis rested on echocardiographic estimation rather than right heart catheterisation. Fistula status, dialysis and advanced CKD stage are strongly collinear, and no multivariable analysis was performed, so their independent contributions cannot be separated. Fistula flow volume, parathyroid hormone and inflammatory markers were not measured, and ongoing treatment with phosphate binders or erythropoiesis-stimulating agents was not recorded.

Among 64 patients with chronic kidney disease, of whom 17 (26.6%) had echocardiographic pulmonary hypertension, a distinct and coherent profile emerged. Patients with pulmonary hypertension had significantly lower haemoglobin (8.38 versus 9.84 g/dL, p = 0.005), significantly lower serum calcium (7.88 versus 9.25 mg/dL, p = 0.0001) and significantly higher serum phosphorus (3.49 versus 2.87 mg/dL, p = 0.0001). Serum creatinine, blood urea and serum albumin did not differ significantly. Pulmonary hypertension was significantly more prevalent among patients with an arteriovenous fistula (45.8% versus 15.0%, p = 0.01) and showed a non-significant trend towards higher prevalence on maintenance haemodialysis (34.1% versus 13.0%, p = 0.07). The pattern is mechanistically informative. Pulmonary hypertension in chronic kidney disease tracked with anaemia, with disordered mineral metabolism and with the haemodynamic burden of vascular access, but not with the conventional markers of azotaemia. This argues that the condition arises from high-output physiology and pulmonary vascular calcification rather than from nitrogenous waste retention as such, and it implies that severity of renal impairment measured by creatinine alone will not identify patients at risk. Clinically, this supports a strategy of aggressive anaemia correction and strict control of calcium–phosphate balance through dietary restriction, phosphate binders and vitamin D analogues, alongside periodic echocardiographic surveillance in patients with an arteriovenous fistula. Where pulmonary hypertension is severe and fistula flow is high, assessment of access flow volume and consideration of flow-reduction procedures may be warranted. Larger multicentre studies with catheter confirmation, multivariable adjustment for the collinearity between dialysis, access and CKD stage, and measurement of parathyroid hormone and fistula flow are required to confirm these associations and to test whether they are causal and reversible.

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