Adrenal Function After Living Kidney Donation
Condition: Addison Disease; Hypoaldosteronism
MeSH terms: Addison Disease; Hypoaldosteronism
Study type: Observational

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 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.
    

Intervention name(s): Laparoscopic hand-assisted donor nephrectomy
Intervention type(s): Procedure
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
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.
      
Keywords: Kidney donation; Organ Donation; Vascular anatomy; Adrenal Insufficiency