Pulmonary Hypertension in Renal Disease: Epidemiology, Potential Mechanisms and Implications

Abstract

Pulmonary hypertension (PH) is highly prevalent in end-stage renal disease. Several observational studies, based on an echocardiographic diagnosis of PH, have suggested a prevalence of 30-60% and an association with increased mortality and poorer outcome following renal transplantation. The pathogenesis of PH in this population remains poorly understood. Reported associations include arteriovenous fistulae, cardiac dysfunction, fluid overload, bone mineral disorder and non-biocompatible dialysis membranes. However, due to the small numbers, the cross-sectional nature of the majority of studies in this field, and the reliance on echocardiography for the diagnosis of PH, no consistent association with any individual risk factor has been demonstrated. There is no difference in prevalence between patients receiving different dialysis modalities and emerging evidence suggests that the onset of the condition may precede dialysis treatment in many patients. Furthermore, little is known about the impact of the ‘uraemic vasculopathy' on the pulmonary vasculature. Given the similarities between vascular changes in uraemia and those seen in pulmonary arterial hypertension, it is possible that a pulmonary vasculopathy may be present in a proportion of patients. There is a need for better understanding of the natural history and the pathogenesis of the condition which would help to individualise treatment of PH in end-stage renal disease. To enable such understanding, prospective adequately powered studies with an integrated investigational approach including right heart catheterisation are needed.

Presence and Outcomes of Kidney Disease in Patients with Pulmonary Hypertension

“…In CKD, higher PAP was noted in those patients with higher PCWP. In addition, previous studies have speculated on the potential influence of uremic toxins, bone-mineral disorder, and endothelial dysfunction on outcomes among those PH patients who are on dialysis (23,27,28). Particularly, these reports note that nitric oxide levels are reduced along with an attenuated release of nitric oxide in those patients on hemodialysis with PH.…”

“…Recent systematic reviews studying PH in the kidney disease population highlighted several other studies addressing the higher prevalence and consequences of PH in both hemodialysis and peritoneal dialysis populations (21)(22)(23). These reviews highlighted the lack of data relating to prevalence and effects of PH in those patients with nondialysis-dependent CKD (22).…”

Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKD

“…[7][8][9][10] PH, defined by elevated pulmonary arterial pressure, is rare in the general population but seen in 30%-40% of patients with ESRD (on the basis of echocardiographic studies). 11,12 After it is established, PH is often progressive and associated with high morbidity and mortality.…”

Pulmonary hypertension in renal transplant candidates: A systematic review and meta-analysis of the available evidence and a proposed algorithm for pre-transplant management

“…The pathogenesis of PHT in this population remains poorly understood with reported associations including AV fistulae, cardiac dysfunction, fluid overload, bone mineral disorders, non-biocompatible dialysis membranes, uremia-induced endothelial dysfunction [21,22].…”