The Living Kidney Donor Safety Study

NCT ID: NCT00936078

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1438 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2022-03-31

Brief Summary

The main goal of this study is to understand the long-term effects of kidney donation on blood pressure, kidney function, and patient-reported health-related quality of life. Living kidney donors and non-donor controls will be studied before and after the living donor transplant. The donors and non-donors will be followed for a minimum of 5 years and a maximum of 15 years. Both groups will be made up of healthy normotensive adults. The purpose of this study is to see if there are any long-term differences between the two groups regarding:

1. risk of hypertension

2. rate of kidney decline

3. risk of albuminuria

4. changes in health-related quality of life

The study also looks to assess other outcomes, including:

1. understand and quantify the expenses incurred by donors

2. understand donor factors which influence recipient outcomes

The pilot version of this study (The Long Term Medical and Psychological Implications of Becoming a Living Kidney Donor: A Prospective Pilot Study) began in 2004. Donors and controls in the pilot study were given the opportunity to continue on in the main study once it started in 2009.

Detailed Description

Transplantation is the preferred treatment option for patients with kidney failure. Compared to dialysis, patients who receive a transplant have a substantial reduction in the risk of death, an improved quality of life, and decreased health care costs. The demand for kidneys has resulted in long waiting lists for deceased donor kidneys. Therefore, living kidney donations have been on the increase over the years in order to meet this demand for kidneys. Living donation also has the added benefit of a shorter waiting time, increased graft success and increased recipient survival compared to deceased donor transplantation.

Aside from the advantages for the recipient, living transplantation is a complex medical practice which we must conduct in a safe and ethical manner. The premise for accepting living donors is that the "minimal" risk of short and long-term medical harm realized by the donor is outweighed by the definite advantages to the recipient and potential psychosocial benefits of altruism to the donor. The short-term potential medical consequences for living kidney donors have been well established. Yet, the long-term implications of living kidney donation are far less certain. Potential medical risks include hypertension, reduced kidney function, albuminuria, premature cardiovascular disease, and death. Estimates of these outcomes vary substantially in the literature. As well, the potential long-term medical risks are also communicated inconsistently across transplant communities. It is accepted that most living donors experience increased self-esteem, feelings of well-being and an improved quality of life after their altruistic act. However, some donors have negative psychosocial outcomes which require further clarification. There is also a financial burden to the donor from the donation process. Concerns about future life, disability, and medical insurance have been raised. These issues will be addressed through this research study on the long term implications of donation. A better understanding of post-donation risk and the timing of new disease onset is critical for donor selection, informed consent, and follow-up. The study will assess the attributable risk of living kidney donation using study techniques that meet modern criteria for high methodological quality. Non-donors will have similar indicators of baseline health as donors and will complete the same schedule of follow-up assessments.

Data was collected as follows:

1. Pre-donation/baseline (informed consent was obtained, eligibility was assessed, surveys were completed, a basic physical exam was completed, blood and urine samples were collected and training on the home blood pressure machine was completed). This occurred for both donors and non-donor controls either on site or long distance.

2. Three months post-donation (mailed 3 month surveys)

3. Annual post-donation follow-up visits (mailed surveys and blood pressure machine, lab testing completed). The number of annual follow-up visits varied depending on the year of nephrectomy, or simulated nephrectomy year for controls (between 5 years to 15 years)

Living kidney donation is practiced with the expectation that minimal risks of donor harm are outweighed by psychological benefits of altruism to the donor and improved recipient health. Our multicentre prospective cohort study of living kidney donors will inform the practice and safety of living kidney donation, including transplant center medical policies on donor selection, patient counseling, informed consent, and long-term patient follow-up and care.

Conditions

Living Kidney Donation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Non-donors/controls

Healthy normotensive people who have not donated a kidney including relatives or friends of the donor, or candidates who were ineligible to donate due to blood group or cross-match incompatibility. These non-donor/controls must meet all screening criteria (same as standard criteria donors).

No interventions assigned to this group

Living Kidney Donors

Living kidney donors who went on to donate their kidney. All donors were recruited and are divided into 2 groups:

1. Standard criteria donors (meet all screening criteria)

2. Expanded-criteria donors (did not meet one or more of the screening criteria)

Expanded criteria donors will be examined in a separate protocol and analysis.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Be able to speak and read English and/or French, and
• Be able to provide informed consent, and

AND

Subjects must either:

• Be approved by the LHSC team (or applicable medical team at the participating sites) as eligible to donate their kidney and donated a kidney,

OR

• Meet study eligibility for controls (non-donors) as follows:

Be between the ages of 18 and 70 years

Meet blood pressure criteria as follows:

• Blood pressure <140 mmHg systolic and <90 mmHg diastolic based on an average of at least 3 blood pressure measurements taken during the recruitment interview, or an average blood pressure < 140 mmHg systolic and < 90 mmHg diastolic based on a minimum of 12 readings taken at home.
• All participants need to successfully record at least 12 home blood pressure readings using the self-monitoring device to be eligible

Meet local lab criteria as follows:

• Documented pre-donation serum creatinine <115 µmol/L in men or <90 µmol/L in women, or Cockcroft-Gault estimated glomerular filtration rate >80 mL/min
• Urine dipstick test for protein is negative or if trace or 0.3 g/L, a random urine albumin to creatinine ratio <8 mg/mmol (70 mg/g)
• Urine dipstick test for hematuria is negative. Those with non-persistent hematuria are eligible to participate. Those with initial evidence of dipstick hematuria may have a second assessment. Test should not occur during menses. Test should be repeated if there is evidence of urinary tract infection once treated.
• Have a body mass index of <35 kg/m2

Exclusion Criteria

• Be involved in another clinical study that would affect the outcome of this study.

AND

Control (non-donor) subjects must not:

• Ever have received dialysis, even for a short period of time
• Ever have had a kidney transplant
• Be taking any hypertension class medication for any reason
• Have any history of hypertension, currently or in the past
• Have plasma glucose of >7 mmol/L after a 6 hour fast (if available), or a two hour oral glucose test of >11.1 mmol/L (if available), or have a history of diabetes during pregnancy
• Have been symptomatic or had evidence of kidney stones any time in the past 3 years
• Have a known contraindication to anesthesia or surgery
• Be currently pregnant or have been pregnant in the past month
• Have a medical condition that would prevent him or her from becoming a kidney donor (e.g. history of renal disease, permanent protein in urine, cancer other than cured non-melanoma skin cancer, cardiovascular disease, pulmonary disease, diabetes)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Astellas Pharma Canada, Inc.

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

Amit Garg

Associate Dean (Clinical Research - Schulich School of Medicine and Dentistry); Professor (Medicine - Western University); Nephrologist (London Health Sciences Centre); Director (ICES Western Facilitly) (As of October 19 2022)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amit Garg, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre

Locations

Sir Charles Gairdner Hospital

Perth, , Australia

Foothills Medical Centre

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

Queen Elizabeth II Hospital

Halifax, Nova Scotia, Canada

St. Joseph's Hospital

Hamilton, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

The Montreal General Hospital

Montreal, Quebec, Canada

Countries

Australia; Canada

References

Garg AX, Arnold JB, Cuerden M, Dipchand C, Feldman LS, Gill JS, Karpinski M, Klarenbach S, Knoll GA, Lok C, Miller M, Monroy-Cuadros M, Nguan C, Prasad GVR, Sontrop JM, Storsley L, Boudville N. The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study. Can J Kidney Health Dis. 2022 Oct 28;9:20543581221129442. doi: 10.1177/20543581221129442. eCollection 2022.

Reference Type: BACKGROUND

PMID: 36325263 (View on PubMed)

Garcia-Ochoa C, Feldman LS, Nguan C, Monroy-Caudros M, Arnold JB, Barnieh L, Boudville N, Cuerden MS, Dipchand C, Gill JS, Karpinski M, Klarenbach S, Knoll G, Lok CE, Miller M, Prasad GVR, Sontrop JM, Storsley L, Garg AX. Impact of Perioperative Complications on Living Kidney Donor Health-Related Quality of Life and Mental Health: Results From a Prospective Cohort Study. Can J Kidney Health Dis. 2021 Aug 11;8:20543581211037429. doi: 10.1177/20543581211037429. eCollection 2021.

Reference Type: RESULT

PMID: 34394947 (View on PubMed)

Habbous S, Arnold J, Begen MA, Boudville N, Cooper M, Dipchand C, Dixon SN, Feldman LS, Gozdzik D, Karpinski M, Klarenbach S, Knoll GA, Lam NN, Lentine KL, Lok C, McArthur E, McKenzie S, Miller M, Monroy-Cuadros M, Nguan C, Prasad GVR, Przech S, Sarma S, Segev DL, Storsley L, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Duration of Living Kidney Transplant Donor Evaluations: Findings From 2 Multicenter Cohort Studies. Am J Kidney Dis. 2018 Oct;72(4):483-498. doi: 10.1053/j.ajkd.2018.01.036. Epub 2018 Mar 24.

Reference Type: RESULT

PMID: 29580662 (View on PubMed)

Przech S, Garg AX, Arnold JB, Barnieh L, Cuerden MS, Dipchand C, Feldman L, Gill JS, Karpinski M, Knoll G, Lok C, Miller M, Monroy M, Nguan C, Prasad GVR, Sarma S, Sontrop JM, Storsley L, Klarenbach S; Donor Nephrectomy Outcomes Research (DONOR) Network. Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort Study. J Am Soc Nephrol. 2018 Dec;29(12):2847-2857. doi: 10.1681/ASN.2018040398. Epub 2018 Nov 7.

Reference Type: RESULT

PMID: 30404908 (View on PubMed)

Barnieh L, Klarenbach S, Arnold J, Cuerden M, Knoll G, Lok C, Sontrop JM, Miller M, Ramesh Prasad GV, Przech S, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Nonreimbursed Costs Incurred by Living Kidney Donors: A Case Study From Ontario, Canada. Transplantation. 2019 Jun;103(6):e164-e171. doi: 10.1097/TP.0000000000002685.

Reference Type: RESULT

PMID: 31246933 (View on PubMed)

Garcia-Ochoa C, Feldman LS, Nguan C, Monroy-Cuadros M, Arnold J, Boudville N, Cuerden M, Dipchand C, Eng M, Gill J, Gourlay W, Karpinski M, Klarenbach S, Knoll G, Lentine KL, Lok CE, Luke P, Prasad GVR, Sener A, Sontrop JM, Storsley L, Treleaven D, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Perioperative Complications During Living Donor Nephrectomy: Results From a Multicenter Cohort Study. Can J Kidney Health Dis. 2019 Jul 18;6:2054358119857718. doi: 10.1177/2054358119857718. eCollection 2019.

Reference Type: RESULT

PMID: 31367455 (View on PubMed)

Barnieh L, Arnold JB, Boudville N, Cuerden MS, Dew MA, Dipchand C, Feldman LS, Gill JS, Karpinski M, Klarenbach S, Knoll G, Lok C, Miller M, Monroy M, Nguan C, Prasad GVR, Sontrop JM, Storsley L, Garg AX; Donor Nephrectomy Outcomes Research (DONOR) Network. Living Kidney Donors' Financial Expenses and Mental Health. Transplantation. 2021 Jun 1;105(6):1356-1364. doi: 10.1097/TP.0000000000003401.

Reference Type: RESULT

PMID: 33741846 (View on PubMed)

Barnieh L, Kanellis J, McDonald S, Arnold J, Sontrop JM, Cuerden M, Klarenbach S, Garg AX, Boudville N; Donor Nephrectomy Outcomes Research (DONOR) Network. Direct and indirect costs incurred by Australian living kidney donors. Nephrology (Carlton). 2018 Dec;23(12):1145-1151. doi: 10.1111/nep.13205.

Reference Type: RESULT

PMID: 29215180 (View on PubMed)

Garg AX, Arnold JB, Cuerden MS, Dipchand C, Feldman LS, Gill JS, Karpinski M, Klarenbach S, Knoll G, Lok CE, Miller M, Monroy-Cuadros M, Nguan C, Prasad GVR, Sontrop JM, Storsley L, Boudville N. Hypertension and Kidney Function After Living Kidney Donation. JAMA. 2024 Jul 23;332(4):287-299. doi: 10.1001/jama.2024.8523.

Reference Type: RESULT

PMID: 38780499 (View on PubMed)

Other Identifiers

6056 (15974E)

Identifier Type: OTHER

Identifier Source: secondary_id

R-09-117

Identifier Type: -

Identifier Source: org_study_id