Addison DiseaseNCT00251836
Adrenal Function After Living Kidney Donation
An observational study of Addison Disease and Hypoaldosteronism, run by University of Zurich at 1 site in Switzerland.
Trial summary
The success of kidney transplantation is hampered by the shortage of organs. One attractive strategy is the use of kidneys from living donors. During the donor operation the kidney artery, kidney vein and ureter have to be interrupted as far as possible from the kidney to have sufficient length for the reconnection of… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Addison Disease, Hypoaldosteronism
- What is being tested?
- Laparoscopic hand-assisted donor nephrectomy
- Type of treatment
- Surgery or procedure
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2007to Apr 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All eligible living donors were considered for participation in the study unless exclusion criteria were present: active corticoid medication, known adrenal disease such as hypercortisolism, hyperaldosteronism or adrenal insufficiency, or the presence of metallic implants precluding MRI investigation. All living kidney donor candidates underwent a standard somatic and psychological eligibility testing during a brief hospitalization in accordance with the Swiss Transplantation Act and the guidelines of the Swiss Academy of Medical Sciences.
Who may be able to join
- Eligible kidney donor (meeting institutional selection criteria)
- Informed consent for study participation
Who cannot join
- Treatment with glucocorticoids
- Preexisting diseases of adrenal function (hypercortisolism, hyperaldosteronism, adrenal insufficiency)
- Inability to undergo MRI examination (metal implants, etc.)
- Inability to understand the study information and to give informed consent (in German)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Dept. of Visceral and Transplantation Surgery, University Hospital Zurich
Zurich, Canton of Zurich, 8091
About this study
Official title: Prospective Evaluation of Adrenal Function After Living Donor Nephrectomy With or Without Ligation of the Adrenal Vein
The success of kidney transplantation is hampered by the shortage of organs. One attractive strategy is the use of kidneys from living donors. During the donor operation the kidney artery, kidney vein and ureter have to be interrupted as far as possible from the kidney to have sufficient length for the reconnection of these structures in the transplant operation.
An adrenal gland is situated at the upper pole of each kidney. While the arterial supply is accomplished by many small vessels, the venous drainage is only through one vein. On the right side the adrenal vein empties directly into the inferior vena cava (the large vessel transporting blood from the lower body to the heart). In contrast, on the left side the adrenal vein empties into the kidney vein, which in turn drains to the inferior vana cava. Due to these anatomical differences a left-sided removal of a kidney always necessitates an interruption of the left adrenal vein, while a right-sided kidney removal does not.
As the venous drainage of the left adrenal gland is closed during living kidney donation, the gland is most likely functionally impaired. This can be compared to a right-sided kidney donation, where the adrenal vein is left intact. These comparisons are performed by adrenal function tests before, one week after and one month after kidney donation. These function tests consist of blood values drawn after stimulation with a hormone drug.
Read the detailed description
Due the lack of suitable donor organs a large proportion of kidney transplantations is now performed from living donors. In the year 2002 the number of living donors surpassed the number of cadaveric donors in Switzerland (Swisstransplant, Swiss Transplant Society 2005). Kidney grafts from living donors have superior long-term outcome (Hariharan S, N Engl J Med 2000). At the University Hospital Zurich 28 of the 84 kidney transplantations performed in the year 2004 were from living donors.
During living donor nephrectomy the renal artery and renal vein are transected as far away from the kidney as possible, to ensure an adequate vessel length for the subsequent transplantation procedure. The arterial supply of the adrenal glands is accomplished by several small vessels (ca. 5-15), while the venous drainage is usually dependent on a single vein. While the right-sided adrenal vein drains directly into the inferior vena cava (IVC), the left-sided adrenal vein drains into the renal vein. Variants are relatively rare and occur in 5% of cases (Sebe P, Surg Radiol Anat 2002). Therefore, during donor nephrectomy of the left kidney the adrenal vein is transected, while this is not necessary on the right side.
The question addressed in this clinical trial is whether left-sided donor nephrectomy affects the left adrenal gland. This might be compensated immediately by the contralateral gland or it might lead to a measurable functional adrenal deficit. Such an adrenal insufficiency could be detrimental to the immediate postoperative course. The intermediate-term outcome of the adrenal glands is also of interest, as an impairment of the left adrenal gland will lead to a hypertrophy of the contralateral gland.
Few scientific publications have addressed these questions. There are case reports of acute intra- and postoperative adrenal insufficiency in patients undergoing nephrectomy with adrenalectomy (Cassinello Ogea C, Rev Esp Anestesiol Reanim 2002, Henrich WL, Urology 1976, Messiant F, Ann Fr Anesth Reanim 1993, Safir MH, Geriatr Nephrol Urol 1998). A small prospective study in patients undergoing radical nephrectomy (including adrenalectomy) did not find signs of adrenal insufficiency (Bischoff P, Anaesthesist 1997). However a subgroup analysis of a newer study demonstrated adrenal insufficiency in radical versus adrenal-sparing nephrectomy (Yokoyama H, BJU Int 2005).
The study hypothesis is that left-sided donor nephrectomy (i.e. with transaction of the adrenal vein) is deleterious to the left adrenal gland and causes a measurable transient adrenal insufficiency after the operation. The primary study endpoint is the assessment of adrenal function after donor nephrectomy. This is done by an ACTH stimulation test, performed at baseline, in the first week after the operation and 4 weeks after the operation. Comparisons are performed between baseline and postoperative values, as well as between left-sided kidney donors (n=20) and right-sided kidney donors (n=10). A secondary study endpoint is to assess the morphological response of both adrenal glands after donor nephrectomy. To this end MRI and volumetry of the adrenal glands is performed at the same time points, with the hypothesis that left-sided nephrectomy will lead to an involution of the left adrenal followed by hypertrophy of the right adrenal.
- Conditions
- Addison Disease, Hypoaldosteronism
- Being tested
- Laparoscopic hand-assisted donor nephrectomy
- Keywords
- Kidney donation, Organ Donation, Vascular anatomy, Adrenal Insufficiency
- Medical subject headings
- Addison Disease, Hypoaldosteronism, Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laparoscopic hand-assisted donor nephrectomyProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Left-sided donor nephrectomy | Left-sided laparoscopic hand-assisted donor nephrectomy Receives: Procedure: Laparoscopic hand-assisted donor nephrectomy | |
| Right-sided donor nephrectomy | Right-sided laparoscopic hand-assisted donor nephrectomy Receives: Procedure: Laparoscopic hand-assisted donor nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma cortisol response to low-dose ACTH stimulation
Low-dose ACTH1-24 stimulation test was conducted by drawing blood at 8 am, then injecting 1 Ig of Synacthen intravenously and drawing further blood samples after 30, 60, and 90 minutes
Measured: Pre-operative, day 1 and day 28 after kidney donation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2005 (estimated)
- Study startJan 2007
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Addison DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Responsible party
- Sponsor
- Investigators
- Markus Weber, MD, Principal investigator, Dept. of Visceral and Transplantation Surgery, University Hospital Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00251836
- Sponsor's protocol ID
- StV 34-2005
- Other IDs
- RAB-F-02-0046
- Status last verified
- Dec 2016
- First submitted
- 8 Nov 2005
- Last updated
- 29 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000 Mar 2;342(9):605-12. doi: 10.1056/NEJM200003023420901.
PubMed 10699159Sebe P, Peyromaure M, Raynaud A, Delmas V. Anatomical variations in the drainage of the principal adrenal veins: the results of 88 venograms. Surg Radiol Anat. 2002 Aug-Sep;24(3-4):222-5. doi: 10.1007/s00276-002-0021-x. Epub 2002 Jun 13.
PubMed 12375078Cassinello Ogea C, Giron Nombiela JA, Ruiz Tramazaygues J, Izquierdo Villarroya B, Sanchez Tirado JA, Almajano Dominguez RM, Oro Fraile J. [Severe perioperative hypotension after nephrectomy with adrenalectomy]. Rev Esp Anestesiol Reanim. 2002 Apr;49(4):213-7. Spanish.
PubMed 14606383Henrich WL, Goldberg J, Lucas M, Gabow P. Adrenal insufficiency after unilateral radical nephrectomy. Urology. 1976 Dec;8(6):584-5. doi: 10.1016/0090-4295(76)90525-2.
PubMed 997054Messiant F, Duverger D, Verheyde I, Declerck N, Pruvot FR, Scherpereel P. [Postoperative acute adrenal insufficiency]. Ann Fr Anesth Reanim. 1993;12(6):594-7. doi: 10.1016/s0750-7658(05)80629-x. French.
PubMed 8017676Safir MH, Smith N, Hansen L, Kozlowski JM. Acute adrenal insufficiency following unilateral radical nephrectomy: a case report. Geriatr Nephrol Urol. 1998;8(2):101-2. doi: 10.1023/a:1008305627588.
PubMed 9893218Bischoff P, Noldus J, Harksen J, Bause HW. [The necessity for perioperative cortisol substitution. Spontaneous and stimulated ACTH and cortisol secretion during unilateral adrenalectomy for renal cell carcinoma]. Anaesthesist. 1997 Apr;46(4):303-8. doi: 10.1007/s001010050405. German.
PubMed 9229984Yokoyama H, Tanaka M. Incidence of adrenal involvement and assessing adrenal function in patients with renal cell carcinoma: is ipsilateral adrenalectomy indispensable during radical nephrectomy? BJU Int. 2005 Mar;95(4):526-9. doi: 10.1111/j.1464-410X.2005.05332.x.
PubMed 15705073
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Adrenal Function After Living Donor Nephrectomy With or Without Ligation of the Adrenal Vein
- ClinicalTrials.gov ID
- NCT00251836
- Acronym / sponsor ID
- StV 34-2005
- Conditions
- Addison Disease, Hypoaldosteronism
- Keywords
- Kidney donation, Organ Donation, Vascular anatomy, Adrenal Insufficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Study start
- Jan 2007
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 10 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The success of kidney transplantation is hampered by the shortage of organs. One attractive strategy is the use of kidneys from living donors. During the donor operation the kidney artery, kidney vein and ureter have to be interrupted as far as possible from the kidney to have sufficient length for the reconnection of these structures in the transplant operation.
An adrenal gland is situated at the upper pole of each kidney. While the arterial supply is accomplished by many small vessels, the venous drainage is only through one vein. On the right side the adrenal vein empties directly into the inferior vena cava (the large vessel transporting blood from the lower body to the heart). In contrast, on the left side the adrenal vein empties into the kidney vein, which in turn drains to the inferior vana cava. Due to these anatomical differences a left-sided removal of a kidney always necessitates an interruption of the left adrenal vein, while a right-sided kidney removal does not.
As the venous drainage of the left adrenal gland is closed during living kidney donation, the gland is most likely functionally impaired. This can be compared to a right-sided kidney donation, where the adrenal vein is left intact. These comparisons are performed by adrenal function tests before, one week after and one month after kidney donation. These function tests consist of blood values drawn after stimulation with a hormone drug.
Detailed description
Due the lack of suitable donor organs a large proportion of kidney transplantations is now performed from living donors. In the year 2002 the number of living donors surpassed the number of cadaveric donors in Switzerland (Swisstransplant, Swiss Transplant Society 2005). Kidney grafts from living donors have superior long-term outcome (Hariharan S, N Engl J Med 2000). At the University Hospital Zurich 28 of the 84 kidney transplantations performed in the year 2004 were from living donors.
During living donor nephrectomy the renal artery and renal vein are transected as far away from the kidney as possible, to ensure an adequate vessel length for the subsequent transplantation procedure. The arterial supply of the adrenal glands is accomplished by several small vessels (ca. 5-15), while the venous drainage is usually dependent on a single vein. While the right-sided adrenal vein drains directly into the inferior vena cava (IVC), the left-sided adrenal vein drains into the renal vein. Variants are relatively rare and occur in 5% of cases (Sebe P, Surg Radiol Anat 2002). Therefore, during donor nephrectomy of the left kidney the adrenal vein is transected, while this is not necessary on the right side.
The question addressed in this clinical trial is whether left-sided donor nephrectomy affects the left adrenal gland. This might be compensated immediately by the contralateral gland or it might lead to a measurable functional adrenal deficit. Such an adrenal insufficiency could be detrimental to the immediate postoperative course. The intermediate-term outcome of the adrenal glands is also of interest, as an impairment of the left adrenal gland will lead to a hypertrophy of the contralateral gland.
Few scientific publications have addressed these questions. There are case reports of acute intra- and postoperative adrenal insufficiency in patients undergoing nephrectomy with adrenalectomy (Cassinello Ogea C, Rev Esp Anestesiol Reanim 2002, Henrich WL, Urology 1976, Messiant F, Ann Fr Anesth Reanim 1993, Safir MH, Geriatr Nephrol Urol 1998). A small prospective study in patients undergoing radical nephrectomy (including adrenalectomy) did not find signs of adrenal insufficiency (Bischoff P, Anaesthesist 1997). However a subgroup analysis of a newer study demonstrated adrenal insufficiency in radical versus adrenal-sparing nephrectomy (Yokoyama H, BJU Int 2005).
The study hypothesis is that left-sided donor nephrectomy (i.e. with transaction of the adrenal vein) is deleterious to the left adrenal gland and causes a measurable transient adrenal insufficiency after the operation. The primary study endpoint is the assessment of adrenal function after donor nephrectomy. This is done by an ACTH stimulation test, performed at baseline, in the first week after the operation and 4 weeks after the operation. Comparisons are performed between baseline and postoperative values, as well as between left-sided kidney donors (n=20) and right-sided kidney donors (n=10). A secondary study endpoint is to assess the morphological response of both adrenal glands after donor nephrectomy. To this end MRI and volumetry of the adrenal glands is performed at the same time points, with the hypothesis that left-sided nephrectomy will lead to an involution of the left adrenal followed by hypertrophy of the right adrenal.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Left-sided donor nephrectomy | – | Procedure: Laparoscopic hand-assisted donor nephrectomyLeft-sided laparoscopic hand-assisted donor nephrectomy |
| Right-sided donor nephrectomy | – | Procedure: Laparoscopic hand-assisted donor nephrectomyRight-sided laparoscopic hand-assisted donor nephrectomy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All eligible living donors were considered for participation in the study unless exclusion criteria were present: active corticoid medication, known adrenal disease such as hypercortisolism, hyperaldosteronism or adrenal insufficiency, or the presence of metallic implants precluding MRI investigation. All living kidney donor candidates underwent a standard somatic and psychological eligibility testing during a brief hospitalization in accordance with the Swiss Transplantation Act and the guidelines of the Swiss Academy of Medical Sciences.
Key inclusion criteria (2 listed)
- Eligible kidney donor (meeting institutional selection criteria)
- Informed consent for study participation
Key exclusion criteria (4 listed)
- Treatment with glucocorticoids
- Preexisting diseases of adrenal function (hypercortisolism, hyperaldosteronism, adrenal insufficiency)
- Inability to undergo MRI examination (metal implants, etc.)
- Inability to understand the study information and to give informed consent (in German)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laparoscopic hand-assisted donor nephrectomy | Procedure or surgery | Left-sided donor nephrectomy, Right-sided donor nephrectomy |
Primary outcome
Plasma cortisol response to low-dose ACTH stimulation
Time frame: Pre-operative, day 1 and day 28 after kidney donation
Low-dose ACTH1-24 stimulation test was conducted by drawing blood at 8 am, then injecting 1 Ig of Synacthen intravenously and drawing further blood samples after 30, 60, and 90 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2016.
- Background: PubMed 10699159Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000 Mar 2;342(9):605-12. doi: 10.1056/NEJM200003023420901.
- Background: PubMed 12375078Sebe P, Peyromaure M, Raynaud A, Delmas V. Anatomical variations in the drainage of the principal adrenal veins: the results of 88 venograms. Surg Radiol Anat. 2002 Aug-Sep;24(3-4):222-5. doi: 10.1007/s00276-002-0021-x. Epub 2002 Jun 13.
- Background: PubMed 14606383Cassinello Ogea C, Giron Nombiela JA, Ruiz Tramazaygues J, Izquierdo Villarroya B, Sanchez Tirado JA, Almajano Dominguez RM, Oro Fraile J. [Severe perioperative hypotension after nephrectomy with adrenalectomy]. Rev Esp Anestesiol Reanim. 2002 Apr;49(4):213-7. Spanish.
- Background: PubMed 997054Henrich WL, Goldberg J, Lucas M, Gabow P. Adrenal insufficiency after unilateral radical nephrectomy. Urology. 1976 Dec;8(6):584-5. doi: 10.1016/0090-4295(76)90525-2.
- Background: PubMed 8017676Messiant F, Duverger D, Verheyde I, Declerck N, Pruvot FR, Scherpereel P. [Postoperative acute adrenal insufficiency]. Ann Fr Anesth Reanim. 1993;12(6):594-7. doi: 10.1016/s0750-7658(05)80629-x. French.
- Background: PubMed 9893218Safir MH, Smith N, Hansen L, Kozlowski JM. Acute adrenal insufficiency following unilateral radical nephrectomy: a case report. Geriatr Nephrol Urol. 1998;8(2):101-2. doi: 10.1023/a:1008305627588.
- Background: PubMed 9229984Bischoff P, Noldus J, Harksen J, Bause HW. [The necessity for perioperative cortisol substitution. Spontaneous and stimulated ACTH and cortisol secretion during unilateral adrenalectomy for renal cell carcinoma]. Anaesthesist. 1997 Apr;46(4):303-8. doi: 10.1007/s001010050405. German.
- Background: PubMed 15705073Yokoyama H, Tanaka M. Incidence of adrenal involvement and assessing adrenal function in patients with renal cell carcinoma: is ipsilateral adrenalectomy indispensable during radical nephrectomy? BJU Int. 2005 Mar;95(4):526-9. doi: 10.1111/j.1464-410X.2005.05332.x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus Weber, MD principal investigator
Dept. of Visceral and Transplantation Surgery, University Hospital Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Addison Disease and Hypoaldosteronism, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma cortisol response to low-dose ACTH stimulation (time frame: Pre-operative, day 1 and day 28 after kidney donation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00251836, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2016.