Long-term Risk of Cardiovascular Disease in Living Kidney Donors

NCT07431515 | Completed

• 1 other identifier: 2021 0906 443 003
• Study Type: observational
• Target: 50,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigative team will conduct a population-based, matched retrospective cohort study across Ontario, Alberta, and British Columbia using linked administrative healthcare databases to evaluate the long-term risk of major adverse cardiovascular events (MACE) among living kidney donors compared with matched healthy nondonors. Living kidney donors who donated between 1992 and 2024 will be included and matched 1:10 to a carefully selected population of nondonors based on key demographic and clinical characteristics. The primary outcome is a composite of cardiovascular death, hospital admission for myocardial infarction, or hospital admission for ischaemic stroke. Secondary outcomes will examine each component of the composite separately and all-cause mortality. The results will provide evidence to inform clinical guidelines, support informed decision-making for potential donors and recipients, and guide counselling by transplant clinicians.

Conditions

Living Donor Nephrectomy; Living Kidney Donation; Living Kidney Donor; Living Kidney Donors; Major Adverse Cardiovascular Events (MACE); Mortality; Cardiovascular Disease

Keywords

living kidney donors; living kidney donation; cardiovascular disease; mortality; major adverse cardiovascular events

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiovascular event (MACE)

  Defined as a composite of cardiovascular (CV) death, hospital admission for myocardial infarction, or hospital admission for ischaemic stroke.

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), non-CV death, emigration from the province, or the end of the observation period (March 31, 2025).

Secondary Outcomes (4)

• All-cause mortality

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until death (secondary outcome), emigration from the province, or the end of the observation period (March 31, 2025).

• Cardiovascular death

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until the study outcome (first event), non-CV death, emigration from the province, or end of the observation period (March 31, 2025).

• Hospitalization for myocardial infarction

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), death, emigration from the province, or the end of the observation period (March 31, 2025).

• Hospitalization for ischaemic stroke

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), death, emigration from the province, or the end of the observation period (March 31, 2025).

Other Outcomes (4)

• MACE composite with heart failure

  Donors and matched non-donors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), non-CV death, emigration from the province, or the end of the observation period (March 31, 2025).

• MACE composite with heart failure and revascularization

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), non-CV death, emigration from the province, or the end of the observation period (March 31, 2025).

• Hospitalization for heart failure

  Donors and matched nondonors will enter the cohort between July 1, 1992 and March 31, 2024, and will be followed until study outcome (first event), death, emigration from the province, or the end of the observation period (March 31, 2025).

Study Arms (2)

Living kidney donor cohort

Living kidney donors who had a laparoscopic nephrectomy between July 1, 1992 and March 31, 2024, at transplant centres in the provinces of Ontario, Alberta, and British Columbia. Each nephrectomy date will serve as their cohort entry date.

Procedure: Nephrectomy

Healthy non-donor cohort

A similarly healthy segment of the general provincial population selected using restriction and matching to emulate the health criteria required to be met for living kidney donation. A cohort entry date will be randomly assigned (simulated nephrectomy date) to all residents in the province, according to the distribution of cohort-entry dates among the donor cohort (between July 1, 1992 and March 31, 2024).

Interventions

Nephrectomy PROCEDURE

Receipt of a nephrectomy for living kidney donation

Living kidney donor cohort

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Living kidney donors matched to nondonors from the general population with similar indicators of baseline health.

You may not qualify if:

• Any person with data errors in their database records (such as missing or invalid age; it is expected to exclude very few persons for these reasons). Data errors also include evidence of prior dialysis or a prior solid organ transplant, as such individuals are not eligible to become donors.
• Any person who was not a permanent resident of the province (i.e., patient lives outside of the province, and only came to the province to donate a kidney to the intended recipient). This will include anyone who is not eligible for the province's health insurance plan, anyone whose date of last contact in the databases is less than 1 year after the cohort entry date, and any person without a physician visit in the last 1-year.
• Any person who is \<18 years of age on the date of nephrectomy (as only under exceptional circumstances should a person less than 18 be approved for living donation).
• Any person with data errors in their database records (such as missing or invalid age).
• Any person who was not a permanent resident of the province. This will include anyone who is not eligible for the province's health insurance plan, anyone whose date of last contact in the databases is less than 1 year after the cohort entry date.
• Any person who is \<18 years of age on the cohort entry date.
• Anyone who is pregnant at the time of index date.
• Baseline illnesses and measures of healthcare access from historic records preceding the cohort entry date will be identified. The sample of eligible nondonors will be restricted to persons without a recorded medical condition that could preclude donation. Such recorded medical conditions will include a hospitalization for mental illness in the prior year; an intensive care unit admission in the prior year; a hospitalization for palliative care services in the prior year; multiple hospital admissions in the prior year; high comorbidity (as assessed by the Charlson comorbidity index and adjusted clinical group scores); receipt of home oxygen therapy; residence at a long-term care facility; dementia; any record of prior nephrology consultation or kidney disease (including receipt of dialysis, a kidney biopsy, or a kidney procedure such as a partial or complete nephrectomy); previous solid organ transplant; disorders of the kidneys, ureters, or bladder; any record of cardiovascular disease (congestive heart failure, cardiovascular procedures, myocardial infarction, peripheral vascular disease, abdominal aortic aneurysm repair, ischemic stroke); hypertension in individuals \<50 years of age (persons with this condition are not accepted as donors in Ontario); any record of obstructive sleep apnea; any cancer diagnosis; any liver disease or cirrhosis; diabetes; any serious infection (hepatitis, HIV, infective endocarditis); any record of autoimmune rheumatic conditions (such as rheumatoid arthritis or systemic lupus erythematosus); and any record of alcoholism.
• To ensure the nondonors have the same opportunity as donors to obtain health care services from physicians, nondonors who had no evidence of a family physician visit in the 2 years prior to index will be excluded. Additionally, nondonors with more than 5 family physician visits in the 2 years prior to index will be excluded, as this could suggest an active health issue that needs attention before donation could occur.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Related Publications (12)

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• Li D, Lu W, Shu D, Toh S, Wang R. Distributed Cox proportional hazards regression using summary-level information. Biostatistics. 2023 Jul 14;24(3):776-794. doi: 10.1093/biostatistics/kxac006.

  PMID: 35195675 BACKGROUND

• Young A, Nevis IF, Geddes C, Gill J, Boudville N, Storsley L, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Do biochemical measures change in living kidney donors? A systematic review. Nephron Clin Pract. 2007;107(3):c82-9. doi: 10.1159/000108648. Epub 2007 Sep 21.

  PMID: 17890875 BACKGROUND

• Segev DL, Muzaale AD, Caffo BS, Mehta SH, Singer AL, Taranto SE, McBride MA, Montgomery RA. Perioperative mortality and long-term survival following live kidney donation. JAMA. 2010 Mar 10;303(10):959-66. doi: 10.1001/jama.2010.237.

  PMID: 20215610 BACKGROUND

• Okamoto M, Akioka K, Nobori S, Ushigome H, Kozaki K, Kaihara S, Yoshimura N. Short- and long-term donor outcomes after kidney donation: analysis of 601 cases over a 35-year period at Japanese single center. Transplantation. 2009 Feb 15;87(3):419-23. doi: 10.1097/TP.0b013e318192dc95.

  PMID: 19202449 BACKGROUND

• Mjoen G, Hallan S, Hartmann A, Foss A, Midtvedt K, Oyen O, Reisaeter A, Pfeffer P, Jenssen T, Leivestad T, Line PD, Ovrehus M, Dale DO, Pihlstrom H, Holme I, Dekker FW, Holdaas H. Long-term risks for kidney donors. Kidney Int. 2014 Jul;86(1):162-7. doi: 10.1038/ki.2013.460. Epub 2013 Nov 27.

  PMID: 24284516 BACKGROUND

• Ibrahim HN, Foley R, Tan L, Rogers T, Bailey RF, Guo H, Gross CR, Matas AJ. Long-term consequences of kidney donation. N Engl J Med. 2009 Jan 29;360(5):459-69. doi: 10.1056/NEJMoa0804883.

  PMID: 19179315 BACKGROUND

• Garg AX, Prasad GV, Thiessen-Philbrook HR, Ping L, Melo M, Gibney EM, Knoll G, Karpinski M, Parikh CR, Gill J, Storsley L, Vlasschaert M, Mamdani M; Donor Nephrectomy Outcomes Research (DONOR) Network. Cardiovascular disease and hypertension risk in living kidney donors: an analysis of health administrative data in Ontario, Canada. Transplantation. 2008 Aug 15;86(3):399-406. doi: 10.1097/TP.0b013e31817ba9e3.

  PMID: 18698242 BACKGROUND

• Garg AX, Meirambayeva A, Huang A, Kim J, Prasad GV, Knoll G, Boudville N, Lok C, McFarlane P, Karpinski M, Storsley L, Klarenbach S, Lam N, Thomas SM, Dipchand C, Reese P, Doshi M, Gibney E, Taub K, Young A; Donor Nephrectomy Outcomes Research Network. Cardiovascular disease in kidney donors: matched cohort study. BMJ. 2012 Mar 1;344:e1203. doi: 10.1136/bmj.e1203.

  PMID: 22381674 BACKGROUND

• Fehrman-Ekholm I, Elinder CG, Stenbeck M, Tyden G, Groth CG. Kidney donors live longer. Transplantation. 1997 Oct 15;64(7):976-8. doi: 10.1097/00007890-199710150-00007.

  PMID: 9381544 BACKGROUND

• Boudville N, Prasad GV, Knoll G, Muirhead N, Thiessen-Philbrook H, Yang RC, Rosas-Arellano MP, Housawi A, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Meta-analysis: risk for hypertension in living kidney donors. Ann Intern Med. 2006 Aug 1;145(3):185-96. doi: 10.7326/0003-4819-145-3-200608010-00006.

  PMID: 16880460 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Nephrectomy

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 24, 2026
• Study Start: July 1, 1992
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2025
• Last Updated: March 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share