Association Between Biomarkers and Kidney Function Decline in Pulmonary Hypertension

Association Between Biomarkers and Kidney Function Decline in Patients With Pulmonary Hypertension

The objective of this study is to examine the association between urinary and plasma biomarkers and change in estimated glomerular filtration rate (eGFR) among patients with pulmonary hypertension (PH).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Disease; Pulmonary Hypertension
• Intervention / Treatment: Other: No intervention is planned as part of the study

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

Study Locations

• Germany
  • Hesse
    • Giessen, Hesse, Germany, 35392
      • University Hospital Giessen and Marburg, Campus Giessen, Department of Internal Medicine II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Inpatients admitted at University Hospital Giessen and Marburg, Campus Giessen with suspected or pre-diagnosed PH undergoing RHC

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pulmonary hypertension; Patients with diagnosed PH by right heart catheterization with or without PH-specific treatment	Other: No intervention is planned as part of the study; No intervention is planned as part of the study
No pulmonary hypertension; Patients in whom PH was excluded by right heart catheterization	Other: No intervention is planned as part of the study; No intervention is planned as part of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse kidney events	Number of patients experiencing ≥q of the individual outcomes of the composite outcome of eGFR decline ≥25%, initiation of dialysis, or all-cause mortality	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initiation of dialysis	Number of patients requiring initiation of dialysis during follow-up	Baseline to 12 months
All-cause mortality	Number of patients experiencing all-cause mortality during follow-up	Baseline to 12 months
Kidney function decline	Number of patients with eGFR decline ≥25% from baseline	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worsening PH	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), worsening of PH as diagnosed by right heart catheterization, or cardiovascular death	Baseline to 12 months

Collaborators and Investigators

• Sponsor: University of Giessen
• Collaborators: Icahn School of Medicine at Mount Sinai; University of Virginia
• Investigators: Principal Investigator: Faeq Husain-Syed, MD, University of Gießen

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Renal Insufficiency; Hypertension; Pathological Conditions, Signs and Symptoms; Hypertension, Pulmonary; Renal Insufficiency, Chronic
• Other Study ID Numbers: AZ174/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No