Regulation of the rapid compensatory growth seen in the remaining adrenal gland of rats following unilateral adrenalectomy is poorly understood. The role of adrenocorticotropic hormone (ACTH) is obscure as immunoneutralization of circulating ACTH does not affect the observed compensatory growth or hyperplasia. This finding, together with the fact that mechanical manipulation of one adrenal without extirpation is followed by growth only in the contralateral gland, has led to the concept of neural regulation of compensatory adrenal growth via a loop from one adrenal through the hypothalamus and back to the contralateral gland which is independent of ACTH secretion. We recently showed that peptides from the N terminal of ACTH precursor proopiocortin (POC), not containing the gamma-melanocyte-stimulating hormone (gamma-MSH) sequence, can stimulate adrenal mitogenesis and proposed that normal long-term adrenal growth and proliferation involves post-secretional proteolytic cleavage of pro-gamma-MSH [or N-POC(1-74)] to generate the mitogenic factor N-POC(1-48/49) and a C-terminal fragment N-POC(50-74), or rat gamma 3-MSH. We have now investigated this hypothesis further in rats by selectively quenching different regions of circulating POC peptides with specific antisera and observing the effect on the increases in weight, RNA and DNA normally seen in the remaining gland following unilateral adrenalectomy. Our results, reported here, suggest that neurally mediated proteolytic cleavage of the circulating inactive mitogenic precursor pro-gamma-MSH at the adrenal gland is the major mechanism of control of compensatory growth.

What's known on the subject? and What does the study add? Previously, donors with asymptomatic stones found incidentally on CT were not considered ideal donor candidates because of the presumed risk of morbidity to both the donor and recipient. Increasingly, studies show that these risks are low. This study aims to evaluate the long‐term safety of using ex vivo ureteroscopy to remove the stones from the donor kidney on the bench before donation. Outcomes so far suggest that this technique can safely render a kidney stone‐free before transplantation. This has led to 20 more transplants in our institution than would otherwise be possible. Objectives To evaluate the prevalence of asymptomatic renal stones in our potential donor population. To assess the safety and success of ex vivo ureteroscopy (ExURS) to remove stones from explanted donor kidneys before transplantation. Patients and Methods We conducted a retrospective analysis of 377 computed tomography (CT) angiograms of potential kidney donors between October 2004 and May 2007 to assess the prevalence of asymptomatic renal stones in our donor population. Between October 2005 and October 2011, kidneys from suitable donors underwent ExURS. Stones were removed using basket extraction or were fragmented with holmium laser on bench before transplantation. Immediate and long‐term complications of the transplanted recipients were recorded. Donors were followed with yearly ultrasonography of the remaining kidney in addition to standard follow‐up protocol. Results Review of 377 CT angiograms between October 2004 to May 2007 showed a 5% prevalence of asymptomatic renal stones. Out of 55 potential donors (19 identified between October 2004 to May 2007 and a further 36 identified since May 2007), 20 donors with stones proceeded to donation, with stone size ranging from 2 to 12 mm. Of the patients, 17 proceeded to ExURS. Stones were removed in 10 patients; five with basket retrieval, four with laser fragmentation and one with both laser fragmentation and basket retrieval. There were no early or late allograft stone‐related complications and no evidence of stones on follow‐up imaging at a mean (range) of 10 (1–24) months. There has been no reported stone recurrence in any of the donors to date and no stone on ultrasonography of eight donors with >1‐year follow‐up (mean 26 months, range 12–49 months). Conclusions Asymptomatic renal stones are present in 5% of our donors. ExURS can be safely used to remove stones in these kidneys before transplantation, without the risk of subjecting the donor to an additional stone‐removing procedure. Continued long‐term follow‐up of donors and recipients is still required to ensure the safety of this approach.

No abstract

Summary Living kidney donors are at risk of long‐term end‐stage renal disease, and obesity is an independent risk factor. In our centre, predonation counselling of obese donors concentrates on lifestyle modifications, particularly weight loss and exercise. Whether these recommendations have a sustainable effect after donation remains unknown. We conducted a retrospective analysis of all donors who proceeded to donation between 2012 and 2016. Donors’ body mass index (BMI) was compared between predefined time points using matched pair analysis. Among 303 donors included, 15% were obese at initial assessment. Obese donors were observed to lose weight by the time of donation (mean BMI difference 1.32 kg/m2, P < 0.001), but bounced back to their initial weight at one‐year postdonation (mean BMI difference + 1.47 kg/m2, P < 0.001), which was maintained at two‐year postdonation. While 71% of obese donors lost weight by the time of donation, 56% of them gained that weight back at one year. Our findings underline the success of predonation counselling on lifestyle modification in highly motivated obese donors, although additional strategies are required to sustain weight loss. The impact of weight gain on long‐term risk needs further evaluation. Living donor programmes should provide continued support with lifestyle modifications after donation.

No abstract