LIVE KIDNEY DONATION LONG-TERM HEALTH-RELATED OUTCOME Shiromani Janki The studies described in this thesis were performed at the Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Financial support for the printing of this thesis was generously provided by: Astellas Pharma B.V. Biomedic B.V. Chiesi Pharmaceuticals B.V. ChipSoft Duo-Med BV Erasmus MC Erasmus MC, Afdeling Epidemiologie Erasmus MC, Afdeling Heelkunde Ipsen Farmaceutica B.V. Krijnen Medical Innovations B.V. Nederlandse Transplantatie Vereniging Olympus Nederland BV Pfzer B.V. Samsung Simendo B.V. ISBN: 978-94-6169-999-2 Cover design by: Drawin Janki Layout and printing: Optima Grafsche Communicatie, Rotterdam, The Netherlands Copyright S. Janki, Rotterdam, The Netherlands. No parts of this thesis may be repro- duced, stored in a retrieval system, or transmitted in any form or by any means without permission of the corresponding journals or the author. LIVE KIDNEY DONATION LONG-TERM HEALTH-RELATED OUTCOME Levende nierdonatie: lange termijn gezondheidsuitkomsten Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnifcus Prof.dr. H.A.P. Pols en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op vrijdag 16 december 2016 om 11.30 uur Shiromani Janki geboren te ‘s-Gravenhage PROMOTIECOMMISSIE Promotoren Prof.dr. J.N.M. IJzermans Prof.dr. A. Hofman Overige leden Prof.dr. W. Weimar Prof.dr. E.W. Steyerberg Prof.dr. J.J. Homan van der Heide TABLE OF CONTENTS Chapter 1 General introduction 7 Chapter 2 Live kidney donation: are concerns about long-term safety justifed? 17 - A methodological review Chapter 3 More than a decade after live donor nephrectomy - A prospective 35 cohort study Chapter 4 Five-year follow-up after live donor nephrectomy - Analysis of a 51 prospective cohort within the era of extended donor acceptance criteria Chapter 5 Validation of ultrasonographic kidney volume measurements - A 73 reliable imaging modality Chapter 6 Impact after live donor nephrectomy - A long-term comparative 89 follow-up study Chapter 7 General discussion, recommendations and future perspectives 109 Chapter 8 Summary in English and Dutch 117 Appendices 131 Contributing authors 133 Dankwoord 137 List of publications 141 PhD Portfolio 145 Curriculum Vitae 149 Chapter 1 General introduction Shiromani Janki Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands Adapted from: Surgical aspects of live kidney donation - An updated review Frontiers of Bioscience (Elite Edition). 2015 Jan 1;7:346-65 Long-term follow-up after live kidney donation (LOVE) study: a longitudinal comparison study protocol BMC Nephrology 2016 Feb 1;17(1):14 General introduction 9 The kidneys are two bean shaped organs, each about 10cm in length, located under the diaphragm at the rear of the abdominal cavity in the retroperitoneal space behind 1 the intestines. Blood supply is received from direct branches of the abdominal aorta, the left and right renal artery and after f ltration the blood drains into the left and renal vein respectively, which connect with the inferior vena cava. Each kidney contains up to a million functioning units called nephrons (Figure 1). A nephron consists of a f ltering unit of tiny blood vessels called a glomerulus attached to tubules. When blood enters the glomerulus, it is f ltered and the remaining f uid then passes along the tubules. In the tubules, chemicals and water are either added to or removed from this f ltered f uid according to the body’s need, the f nal product is the urine we excrete. The kidney is an essential organ, which plays a pivotal role in acid/base balance, sodium/potassium balance, calcium metabolism, regulation of blood pressure, red blood cell synthesis, and excretion of metabolites. Figure 1. Kidney and nephron A progressive loss in kidney function could ultimately lead to end-stage renal disease (ESRD), where kidneys are no longer able to remove waste and excess water from the body and patients require renal replacement therapy to survive. Renal replacement therapy may consist of maintenance dialysis or renal transplantation. Renal transplanta- tion of ers a better prognosis and long-term benef t to patients with ESRD compared with other renal replacement therapies1. 10 Chapter 1 In the early 1950s, Rene Kuss and Joseph Murray performed the frst successful kidney transplantations using identical twins as live donors in France and the United States, 2,3 respectively . The invention of adequate immunosuppressive therapy in the 1960s enabled deceased donor kidney transplantation, preventing risky operations performed on healthy individuals. As enough deceased donors were present at that time, live kid- ney donor transplantation was pushed into the background. In the late 1980s and 1990s, a discrepancy between deceased organ demand and supply occurred due to an increas- ing number of patients sufering from ESRD and a stagnating number of transplants. This prompted renewed interest in live donor kidney transplantation as an alternative. With the increase in the number of live kidney donor transplantations signifcant benefts over kidney transplantation from a deceased donor were demonstrated: superior organ 1 quality, increased graft survival and the possibility of pre-emptive transplantation . 4-7 Live kidney donation has been proven to be a safe surgical procedure with a very 8,9 low mortality rate . Justifed by all these excellent results a signifcant increase in live kidney donations was observed. Thus, live donor kidney transplantation has helped to narrow the gap between deceased organ shortage and the number of ESRD patients on 10 the transplant waiting list . Nevertheless, a shortage in donor kidneys still remains, and against this background an extension of the donor acceptance criteria was observed in recent years; donors with comorbidities such as cardiovascular disease, obesity and 11,12 higher age are no longer denied for donation . As a result, nearly 30,000 transplants from live kidney donors are annually performed worldwide, and this number has re- 13,14 mained stable over the past decade . With the extension of donor acceptance criteria we must be attentive to the potential efect on the donor’s health, as any harm to the donor has to be prevented. Live kidney donation is possible because of the capacity of the remnant kidney to physiologically compensate for the decrease in kidney function by hyperfltration and increase in kidney 15-21 volume . Increase in volume of the remnant kidney can be considered as the physi- ological response to adapt for the decrease in kidney function. To assess which individu- als are suitable for live kidney donation potential donors are exhaustively screened by a multidisciplinary team of nephrologists, transplant surgeons and anesthesiologists prior to donation. Medical suitability of the donor is assessed by using criteria defned by the Amsterdam Forum, a group of experts that developed an international standard of care on live donor evaluation in 2004. They set forth a list of all the (relative) contra-indica- tions to live kidney donation. Donors must have sufcient renal function (GFR more than 80 ml/min), no hypertension (less than 140/90), no obesity (BMI less than 35 kg/m²), negative urine analysis for protein (less than 300mg/24 hours), no diabetes, no kidney stone disease, no malignancy or recurrent urinary tract infections, no or at most a minor 22 cardiovascular or pulmonary risk, no smoking, and no alcohol . In addition to providing