Live kidney donors are healthy volunteers who are exposed to major surgical procedure and physical harms with no direct therapeutic benefits. Efforts to minimize their risks and morbidity are therefore of utmost importance. The current thesis describes studies on donor evaluation, surgical procedure and postoperative management of live kidney donors. The overall purpose is to evaluate and possibly improve routines and treatments in order to reduce risks and the overall morbidity of live kidney donors. In Study I, we evaluated the assessment of kidney function during donor evaluation and found that the accuracy of iohexol glomerular filtration rate (GFR) is compromised by large variations in repeated measurements in presumably healthy donors. We proposed that there is a need for improvement of GFR measurements and that the assessment of predonation kidney function should be more comprehensive, involving GFR, laboratory investigations, functional and morphological examinations and sound clinical judgment. In Study II, we addressed the risk of perioperative venous thromboembolism (VTE) and concluded that expanding the standard screening protocol for VTE to include perioperative venous duplex can potentially decrease the VTE-related morbidity. In studies III and IV, we investigated the impact of hand-assisted retroperitoneoscopic (HARS) nephrectomy on donor safety and perioperative morbidity. The HARS nephrectomy uses the hand-assisted approach, which enables immediate manual compression for hemostasis in case of sudden and severe bleeding. Additionally, the pure retroperitoneal access further increases the safety margin of laparoscopic donor nephrectomy by 1) minimizing the risk of intestinal injury, and 2) exposure of the retroperitoneal nerves, making HARS suitable for continuous infusion of local anesthetics (CILA). CILA effectively reduces the need for opioid consumption and has the potential to totally obviate opiate analgesics postoperatively. Consequently, CILA in combination with HARS reduces morphine-related morbidity and promotes postoperative recovery. In accordance with these data, we recommend improvement and modification of the donor evaluation process as well as a broad introduction of HARS nephrectomy in combination with CILA to increase the safety margin for live kidney donors.

Introduction: Renal transplantation is the treatment of choice for patients with end stage renal disease [ESRD]. An increased risk of ESRD has been demonstrated when comparing donors to age matched healthy non-donors. There are no outcome data in Africa on long term donor renal function or mortality. Therefore, this study aimed to assess long term health complications in the living donor population and evaluate risk factors associated with poor health outcomes of the donors. Methods: This was a retrospective review with prospective follow up of persons undergoing living related donor nephrectomy for renal transplantation, at Groote Schuur Hospital (GSH) from January 2005 to November 2017. We retrospectively analysed baseline demographics, clinical information including blood pressure and renal function (creatinine, eGFR and proteinuria) and compared them with follow up blood pressure and renal function. Results: The majority of the donors were of mixed ancestry 94/154(61%) and 1st degree relatives 111/154 (72%) of which 63/111 (56.8%) donors were siblings. Hypertension developed in 16/31 (51.6%) donors at follow-up. Those developing hypertension had a higher mean baseline blood pressure (systolic blood pressure 139±11.3 mmHg and diastolic blood pressure 85.5±7.3 mmHg). 21/49(42.9%) developed chronic kidney disease [CKD], of which, 16 donors had an eGFR < 60 ml/min/1.73m2 . In those that developed CKD there was a higher percentage of males (p=0.018) and they were older (p=0.048) at baseline. Baseline systolic and diastolic blood pressures was not statistically different in those that developed CKD. 3/31(9.6%) donors developed diabetes. Conclusions: In South Africa, CKD is on the rise and the need for kidney donors for patients with ESRD is therefore also increasing. This study demonstrates that our living donors are at increased risk of CKD and hypertension and therefore need to be followed up more rigorously.

<p>Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough.</p><p>The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN.</p><p>In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function.</p><p>Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches.</p><p>In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.</p>

Live donor nephrectomy (LDN) is a unique surgical challenge where surgery is performed on healthy individuals. It is of great importance to keep the morbidity of donors as low as possible, as well as harvesting a kidney in optimal condition. Lowering morbidity is the motive for introducing the endoscopic technique in LDN. Oliguria and impaired kidney function can, however, be seen during pneumoperitoneum and endoscopic LDN have been criticized for not yet being proven safe enough. The aims of this study were to investigate the changes in renal function during elevated intraabdominal pressure (IAP) in donors and rats and to evaluate donor morbidity and safety of the new endoscopic techniques compared to the open LDN. In two studies, a rat model was used. It was found that elevation of IAP diminished glomerular filtration rate (GFR). Cardiac output (CO) and renal blood flow decreased as well. Elevation of IAP activates the renin system and aldosterone was increased. Acute angiotensin II receptor 1 blockade (candesartan) treatment lowered blood pressure significantly and impaired renal function during elevated IAP. Volume expansion prior to, and during, pneumoperitoneum reduces the deleterious effects on renal function. Three studies on kidney live donors show that traditional laparoscopic surgery (TLS) takes longer time to perform than open LDN. Hand-assistance facilitates the operation and increases the safety margin as well as shortens the operation by 27% compared to TLS. Evaluation of a hand-assisted retroperitoneoscopy (HARS), performed for the first time ever in Uppsala 2001, show that the operation is short and safe, the donors experience little pain and the renal function is favourable compared to open surgery, TLS and hand-assisted transperitoneal laparoscopic approaches. In conclusion, the results indicate that elevated IAP decreases GFR due to decreased CO and activation of the RAAS, which can be avoided with adequate hydration. Endoscopy can be facilitated if hand-assistance is applied and in particular hand-assisted retroperitoneoscopic nephrectomy shows advantages for the donor.