Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) or kidney failure, with an estimated prevalence of up to 78% in those referred for right-heart catheterization. PH is independently associated with adverse outcomes in CKD, raising the possibility that early detection and appropriate management of PH might improve outcomes in at-risk patients. Among patients with PH, the prevalence of CKD stages 3 and 4 is estimated to be as high as 36%, and CKD is also independently associated with adverse outcomes. However, the complex, heterogenous pathophysiology and clinical profile of CKD–PH requires further characterization. CKD is often associated with elevated left ventricular filling pressure and volume overload, which presumably leads to pulmonary vascular stiffening and post-capillary PH. By contrast, a distinct subgroup of patients at high risk is characterized by elevated pulmonary vascular resistance and right ventricular dysfunction in the absence of pulmonary venous hypertension, which may represent a right-sided cardiorenal syndrome defined in principle by hypervolaemia, salt avidity, low cardiac output and normal left ventricular function. Current understanding of CKD–PH is limited, despite its potentially important ramifications for clinical decision making. In particular, whether PH should be considered when determining the suitability and timing of kidney replacement therapy or kidney transplantation is unclear. More research is urgently needed to address these knowledge gaps and improve the outcomes of patients with or at risk of CKD–PH. In this Review, the authors discuss potential pathophenotypes of coexisting chronic kidney disease and pulmonary hypertension, discuss the principles of clinical management of patients with chronic kidney disease or kidney failure and pulmonary hypertension, and outline key areas for further research. Key points: Pulmonary hypertension (PH) is common and independently associated with increased mortality in patients with chronic kidney disease or kidney failure; conversely, chronic kidney disease and kidney failure are common and independently associated with increased mortality in patients with PH. In left-heart cardiorenal syndrome, impaired left ventricular function leads to pulmonary venous hypertension, which promotes pulmonary hypertension as well as renal dysfunction in the setting of renin–angiotensin–aldosterone system overactivation, salt avidity and hypervolaemia. In right-heart cardiorenal syndrome, pulmonary arterial hypertension leads to severe pulmonary arterial remodelling, right-heart failure and impaired cardiac output, despite normal left-heart function. This process promotes kidney failure via neurohumoral, sympathetic and mechanical mechanisms. Major overlap exists in the pathophysiology of pulmonary arterial remodelling and kidney failure, which could serve as the basis for potential therapeutic targets for both conditions. No clear screening algorithms have been established for PH in kidney failure or kidney failure in PH. PH could be a potential surrogate marker for risk of kidney failure, and opportunities may exist to improve outcomes by considering PH when determining the timing and appropriateness of kidney replacement therapy and/or kidney transplantation. [ABSTRACT FROM AUTHOR]