Clinical trial NCT00936078: The Living Kidney Donor Safety Study
Official title: The Living Kidney Donor Safety Study (Long-term Effects of Becoming a Living Kidney Donor)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Living Kidney Donation
Keywords: blood pressure
glomerular filtration rate
hypertension
kidney transplantation
living kidney donation
unilateral nephrectomy
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Astellas Pharma Canada, Inc.
name: Novartis
First posted: 2009-07-09
Enrollment: 1438
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The donors will come from the identified population of people who will be donating their kidney at the hospital sites participating in this study.

The non-donor population will be people who the donors identify and ask to act as their control person. As well, controls will also be found using pamphlet and poster board advertising.

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.

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)

Primary outcomes:
measure: Hypertension
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Secondary outcomes:
measure: Kidney Function
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
measure: Albuminuria
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
measure: Hypertension, an eGFR<60, and/or albuminuria
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Other outcomes:
measure: Death, kidney failure, and major cardiovascular events
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
measure: Tinnitus (tracer outcome)
timeFrame: Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
measure: Physical component summary (PCS) score of the 36-Item Short Form Survey (SF-36)
timeFrame: Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
measure: Mental component summary (MCS) score of the 36-Item Short Form Survey (SF-36)
timeFrame: Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
measure: Beck Depression Index (BDI) score
timeFrame: Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
measure: Beck Anxiety Inventory (BAI) score
timeFrame: Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
Locations:
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Hospital
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: The Montreal General Hospital
state: Quebec
Study officials:
affiliation: London Health Sciences Centre
name: Amit Garg, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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