Editorial Living Kidney Donation: Biochemical Changes and Patient Outcomes

Related Article, p. 577

very year more than 27,000 individuals worldwide choose to undergo living kidney donation to help someone in need.1 The question has been raised of whether the immediate decrement in glomerular ltration rate (GFR) after kidney donation portends the same biochemical changes and patient outcomes as chronic kidney disease (CKD).2 When certain biochemical features and clinical outcomes are observed in patients with CKD, it is difcult to know whether they are attributable entirely to the decrease in GFR. This is because patients with CKD are older and frequently have comorbid conditions that may inuence observed associations. In this issue of AJKD, Kasiske et al3 report the 6-month (interim) results of an important prospective cohort study of approximately 200 living kidney donors and 200 nondonor controls (the ALTOLD [Assessing Long Term Outcomes Of Living Donation] Study; funded by the US National Institutes of Health). Kasiske et al3 offer unique insights into the biochemical effects of mild isolated decrements in GFR after nephrectomy with less confounding than studies of patients with decreased GFR from kidney disease. This study provides more reliable estimates of effects previously described in cross-sectional and retrospective studies of living kidney donors.4,5 In brief, in this study, donors and nondonor controls were prospectively enrolled from 8 transplantation centers in the United States between 2006 and 2011. In order to investigate outcomes associated with kidney donation, it is vital to choose the best type of nondonor controls to compare with donors. Potential donors undergo a thorough selection process, which means that individuals who go on to donate are already inherently healthier than the general population. In the study by Kasiske et al,3 nondonor controls were healthy individuals who theoretically could have been donors at each enrolling site. Controls were screened with a medical history, physical examination, and basic blood and urine laboratory tests for kidney disease, but did not undergo other screening tests, such as renal imaging, that were performed in
Address correspondence to Amit X. Garg, MD, PhD, London Kidney Clinical Research Unit, Room ELL-121, Westminster, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 4G5, Canada. E-mail: amit.garg@lhsc.on.ca 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.06.006
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donors. Assays were done in a single study laboratory. Of the participants, 32% were men, 95% were of white ethnicity, 23% were obese (body mass index 30 kg/m2), and 12% were current smokers; average blood pressure was 117/70 mm Hg. Fifteen percent of nondonor controls and 31% of donors had a family history of a rst-degree relative with kidney failure. One strength of the study is that participants GFRs were measured (iohexol) at baseline and follow-up. Approximately 10% of participants were lost to 6-month follow-up. Kidney donation resulted in a 28% decline in iohexol-measured GFR (average, 97 mL/min/1.73 m2 before donation and 68 mL/min/1.73 m2 6 months after donation). The average decrement observed in measured GFR was comparable to the average decrement observed in estimated GFR, which is reassuring for clinical practice, in which estimated GFR is typically used to follow up donors. Six months after donation, the authors found no substantive difference between donors and nondonor controls in blood pressure, body weight, or body mass index and no difference in lipid, glycemic, or inammatory parameters. Donors had differences in some parameters of mineral metabolism (higher parathyroid hormone and lower serum phosphate levels), slightly lower hemoglobin levels, and higher serum uric acid and homocysteine levels versus controls. The authors conclude that kidney donors have some but not all of the biochemical abnormalities seen with mild CKD, an assertion fully supported by their data. This new knowledge of biochemical changes after donor nephrectomy is welcome. A prospective cohort design, as used in this study, is well suited to describe biochemical, GFR, and blood pressure changes after donor nephrectomy. It also is well suited to understanding the psychosocial outcomes of donation, such as evaluating the adequacy of informed consent, any changes in quality of life or anxiety, and the nancial expenses incurred by donors. However, one of the challenges with a prospective study design is that participants will need to be followed up for decades to characterize many clinically relevant outcomes that matter to donors, recipients, and their health professionals. The threat of lost follow-up is a major concern in long-term prospective studies, and thousands of participants need to be followed up to provide adequate statistical power for reliable estimates of risk. In this regard, the information for clinical and surrogate outcomes from prospective studies can prompt efforts to obtain safety information for patient outcomes in a timely way using other types of study
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designs. For example, studies by Kasiske et al3 and others4,5 now describe changes in levels of markers of bone mineral metabolism in kidney donors; higher levels of serum broblast growth factor 23 (FGF-23), plasma parathyroid hormone, and fractional excretion of urinary inorganic phosphate and lower levels of serum calcitriol and phosphate. To ensure that donors are not experiencing a higher rate of osteoporotic fractures with these biochemical changes, we recently used a retrospective cohort design using large health care databases.6 We were reassured that living kidney donors were not manifesting a higher risk of osteoporotic fractures compared with nondonor controls when followed up for almost 2 decades. In conclusion, different types of study designs will continue to be used to better understand biochemical changes and clinically important long-term outcomes in living kidney donors. This information will inform the decision-making process for potential kidney donors and recipients, strengthen the publics trust in the transplantation system, allow the nephrology community to expand to new types of living donors safely, and guide the follow-up care we provide to donors to maintain optimal long-term health.7 Amit X. Garg, MD, PhD Western University London, Canada

ACKNOWLEDGEMENTS
Support: Dr Garg and colleagues in the Donor Nephrectomy Outcomes Research (DONOR) Network have received investigatorinitiated grants from Astellas and Roche to support a Canadian Institutes of Health Researchfunded prospective study on living kidney donation. Financial Disclosure: The author declares that he has no relevant nancial interests.

REFERENCES
1. Horvat LD, Shariff SZ, Garg AX. Global trends in the rates of living kidney donation. Kidney Int. 2009;75(10):1088-1098. 2. Levey AS, Danovitch G, Hou S. Living donor kidney transplantation in the United Stateslooking back, looking forward. Am J Kidney Dis. 2011;58(3):343-348. 3. Kasiske BL, Anderson-Haag T, Ibrahim HN, et al. A prospective controlled study of kidney donors: baseline and 6-month follow-up. Am J Kidney Dis. 2013;62(3):577-586. 4. Young A, Nevis IF, Geddes C, et al. Do biochemical measures change in living kidney donors? A systematic review. Nephron Clin Pract. 2007;107(3):c82-c89. 5. Young A, Hodsman AB, Boudville N, et al. Bone and mineral metabolism and broblast growth factor 23 levels after kidney donation. Am J Kidney Dis. 2012;59(6):761-769. 6. Garg AX, Pouget J, Young A, et al. Fracture risk in living kidney donors: a matched cohort study. Am J Kidney Dis. 2012; 59(6):770-776. 7. Leichtman A, Abecassis M, Barr M, et al. Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations. Am J Transplant. 2011;11(12): 2561-2568.

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