Association Between Biomarkers and Kidney Function Decline in Pulmonary Hypertension

PH is a severe, progressive disease associated with right ventricular dysfunction, right-sided heart failure (HF) and death. Kidney disease is present in approximately 35% of patients with PH, and its presence is associated with an enhanced risk for adverse outcomes, with the risk increasing incrementally with declining kidney function. Poor right ventricular function may increase venous congestion, alter ventricular interdependence, decrease effective cardiac output and activate the renin-angiotensin- aldosterone system, thereby aggravating kidney disease.

There is a crucial need to better understand the pathophysiological mechanisms linking the failing right heart and the kidney. To date, diagnostic and prognostic biomarkers of kidney disease in PH are lacking. The objective of this study is to examine the association between urinary and plasma biomarkers and change in eGFR among patients with PH.

• No intervention is planned as part of the study (Other): No intervention is planned as part of the study

Primary outcomes

• Major adverse kidney events [Baseline to 12 months]: Number of patients experiencing ≥q of the individual outcomes of the composite outcome of eGFR decline ≥25%, initiation of dialysis, or kidney-related death
• Worsening PH or HF [Baseline to 12 months]: Number of patients experiencing worsening of PH, defined as hospitalization due to acute right heart failure, increase in PH-targeted medication or diuretics (outpatient or inpatient), or worsening of PH as diagnosed by right heart catheterization

Secondary outcomes

• All-cause mortality [Baseline to 12 months]: Number of patients experiencing all-cause mortality during follow-up
• Kidney function decline [12 months]: Number of patients with 50% decline in eGFR from baseline and the eGFR slope at 12 months
• Pulmonary hypertension-related death [12 months]: Death attributed to pulmonary hypertension

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Inpatients aged ≥18 years
* Undergoing right heart catheterization (RHC)

Exclusion Criteria:

* multifactorial or indeterminate PH, for which no single underlying mechanism could be reliably classified
* active tumor disease requiring targeted therapy
* inflammatory or autoimmune disease with renal involvement requiring systemic immunosuppressive treatment
* unexplained kidney function decline, defined as serum creatinine increase ≥0.5 mg/dL from baseline within the prior 7 days before RHC
* Chronic kidney disease with eGFR <20 ml/min/1.73 m2
* non-kidney failure requiring extracorporeal or peritoneal ultrafiltration for diuretic-resistant volume overload
* if they had received non-steroidal anti-inflammatory drugs or intravenous contrast within 72 hours before RHC
* prediagnosed glomerulonephritis
* polycystic kidney disease
* postrenal obstruction
* single kidney (functional or anatomical)
* solid organ transplantation
* anticipated life expectancy of <12 months
* likelihood of receiving advanced therapy (mechanical circulatory assist device/lung or cardiac transplant)
* pregnancy or possibility of pregnancy in the next 12 months
* inability to cooperate with respiratory maneuvers during renal Doppler
* refusal to participate
* not available for follow-up visits

• Husain-Syed F, DiFrancesco MF, Deo R, Barr RG, Scialla JJ, Bluemke DA, Kronmal RA, Lima JAC, Praestgaard A, Tracy RP, Shlipak M, Kawut SM, Kim JS. Associations between eGFR and albuminuria with right ventricular measures: the MESA-Right Ventricle study. Clin Kidney J. 2023 Apr 21;16(9):1508-1520. doi: 10.1093/ckj/sfad096. eCollection 2023 Sep. PMID 37664568
• Results publication: Chakinala MM, Coyne DW, Benza RL, Frost AE, McGoon MD, Hartline BK, Frantz RP, Selej M, Zhao C, Mink DR, Farber HW. Impact of declining renal function on outcomes in pulmonary arterial hypertension: A REVEAL registry analysis. J Heart Lung Transplant. 2018 Jun;37(6):696-705. doi: 10.1016/j.healun.2017.10.028. Epub 2017 Nov 6. PMID 29174533

• Faeq Husain-Syed, MD, Principal investigator, University of Giessen