The Living Kidney Donor Safety Study

Living Kidney Donation Clinical Trial

— LKD  

Official title:

The Living Kidney Donor Safety Study (Long-term Effects of Becoming a Living Kidney Donor)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00936078
• Other study ID #: R-09-117
• Secondary ID: 6056 (15974E)
• Status: Completed
• Start date: September 2009
• Est. completion date: March 2022

Study information

• Verified date: December 2022
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 was started 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1438
• Est. completion date: March 2022
• Est. primary completion date: November 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Living Kidney Donation

Locations

Country	Name	City	State
Australia	Sir Charles Gairdner Hospital	Perth
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Queen Elizabeth II Hospital	Halifax	Nova Scotia
Canada	St. Joseph's Hospital	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	The Montreal General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Health Sciences Centre	Winnipeg	Manitoba

Sponsors (4)

Lead Sponsor	Collaborator
Lawson Health Research Institute	Astellas Pharma Canada, Inc., Canadian Institutes of Health Research (CIHR), Novartis

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (8)

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) Networ — View 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 — View 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, — View Citation

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 Complicat — View 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 A — View 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. — View Citation

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, — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Death, kidney failure, and major cardiovascular events	Death, kidney failure (i.e., a persistent eGFR less than 15 mL/min per 1.73 m2, receipt of dialysis for any duration, or receipt of a kidney transplant), and major cardiovascular events (i.e., myocardial infarction, stroke, or a cardiovascular procedure such as coronary angioplasty or coronary bypass surgery) will be assessed from the annual survey and from medical records, with adjudication conducted by a physician blinded to donation status. These outcomes will be assessed individually and as a composite.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Other	Tinnitus (tracer outcome)	Tinnitus (the perception of chronic ringing or noise in the ears) will be examined as a tracer outcome (i.e., a marker of self-report bias) because it is expected to be similar in donors and non-donors. Donors and non-donors with a history of tinnitus at enrollment will be excluded from this analysis.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Other	Physical component summary (PCS) score of the 36-Item Short Form Survey (SF-36)	The PCS is derived from the following 8 domains of the SF-36 survey: physical functioning, role physical, bodily pain, general health perceptions, energy/vitality, social functioning, role emotional, and mental health. The PCS is scored according to documented procedures using Canadian or Australian normative data as appropriate, and ranges from 0 to 100 with higher scores representing better health status.	Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
Other	Mental component summary (MCS) score of the 36-Item Short Form Survey (SF-36)	The MCS is derived from the following 8 domains of the SF-36 survey: physical functioning, role physical, bodily pain, general health perceptions, energy/vitality, social functioning, role emotional, and mental health. The MCS is scored according to documented procedures using Canadian or Australian normative data as appropriate, and ranges from 0 to 100 with higher scores representing better health status."	Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
Other	Beck Depression Index (BDI) score	Depression will be assessed using the Beck Depression Inventory. The BDI has 21 items and assesses symptoms experienced over the past week. Scores range from 0 (no depression) to 63 (severe depression).	Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
Other	Beck Anxiety Inventory (BAI) score	Anxiety will be assessed using the Beck Anxiety Inventory. The BAI has 21 items and assesses symptoms experienced over the past month. Scores range from 0 (no anxiety) to 63 (severe anxiety).	Annually (one data collection per year) for a maximum of 5 years, occurring up to a maximum of 15 years after donation (baseline)
Primary	Hypertension	Incident hypertension will be adjudicated by a physician who is blinded to the participant's donation status. Adjudication will occur if a participant meets the following criteria in follow-up: (1) the participant reports a physician diagnosis of hypertension, (2) the participant reports taking medication for hypertension, or (3) the participant has a systolic blood pressure (SBP) =140 or a diastolic blood pressure (DBP) =90 mmHg based on the average blood pressure (BP) measurements at any follow-up visit. Stage 1 hypertension will be defined as SBP/DBP 130 to 139/80 to 89 mmHg. We will also assess the average change in SBP and DBP over time accounting for the use of antihypertensive medications. Donors with pre-donation hypertension will be excluded from this primary analysis.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Secondary	Kidney Function	We will assess the annualized change in eGFR over time (in mL/min per 1.73 m2 per year) in donors and non-donors using all available eGFR measurements, setting the starting eGFR value to be the one obtained (1) 1 year after the nephrectomy date (or 1 year after the assigned nephrectomy date for non-donors), (2) 3 years after the nephrectomy date, and (3) at baseline (pre-donation). We will also examine the proportion of participants whose eGFR fell below 60 mL/min per 1.73 m2 in follow-up, the proportion whose eGFR fell below 45 mL/min per 1.73 m2, and the proportion whose eGFR fell below 30 mL/min per 1.73 m2.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Secondary	Albuminuria	We will compare the geometric mean albumin-to-creatinine ratio in donors versus non-donors at the final follow-up visit, adjusted for the baseline (pre-donation) value. Values that are too low to measure will be recoded as 0.2 mg/mmol. We will also examine the proportion of participants who have an albumin-to-creatinine ratio =3 mg/mmol (=30 mg/g) or >30 mg/mmol (>300 mg/g) at any time in follow-up.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)
Secondary	Hypertension, an eGFR<60, and/or albuminuria	We will examine the proportion of participants who develop hypertension, an eGFR <60 mL/min per 1.73 m2, or an albumin-to-creatinine ratio =3 mg/mmol. This outcome will be assessed as a composite, with death (expected to be rare during the follow-up period) treated as a competing event. We will also report the proportions of participants who develop (1) 2 or 3 of these components and (2) all 3 of these components.	Annually (one data collection per year) for a minimum of 5 years to a maximum of 15 years after donation (baseline)