Changes in Renal Function
After surgical donation of a kidney, the remaining kidney hypertrophies and increases single-nephron GFR to compensate for the decrease in nephron mass. After kidney donation, there is a significant drop in GFR with the loss of one kidney. A meta-analysis showed that there is an average 26 mL/min/1.73 m2 decrease in GFR.17 In cases of renal disease, renal hyperfiltration contributes to the progression of CKD.
Whether this process is deleterious to the remaining kidney following living kidney donation is unclear. This is often difficult to interpret given the variable ages of the donors at the time of donation. It is well known that GFR declines with advancing age and whether living kidney donation hastens that process remains unclear. A recent study has suggested that decline in renal function may accelerate with increasing age.19 Other studies, however, suggest that the decline in GFR reflects only the normal decline in renal function associated with the ageing process.5
In a similar study, Gossmann et al. noted a drop in estimated GFR from 92 to 71 mL/min/1.73 m2 over an average of 12 year after donation.11 The study found no correlation with the drop in GFR and time after donation, but showed that the largest declines in GFR were associated with the highest GFRs prior to donation. This suggests that the rate of decline mirrors the age-related decline in GFR. In the study by Ibrahim et al., the average GFR was 76% of the pre-donation GFR. In addition, 85.5% of donors had an iohexol-measured GFR greater than 60 mL/min/1.73 m2. 7
No donor had a GFR below 30 mL/min and the average rate of decline was calculated to be 0.49 mL/min annually. Although living kidney donation does not appear to cause an accelerated decline in GFR, it should be noted that these studies focused on primarily homogenous Caucasian populations, so their applicability to other races is unknown. There is a current concern that outcomes may be significantly worse after living kidney donation in African-American donors.20
Risk of ESRD
The risk of developing ESRD after living kidney donation does not appear to be worse than the general population, supporting the notion that living kidney donation is safe. This is controversial, however. According to the current literature, the risk of developing ESRD after living kidney donation ranges from 0.1% – 1.1%. 21,22 Most studies, however, were not sufficiently powered to provide an accurate assessment of risk.
The study by Ibrahim et al. found that the ESRD rate among living kidney donors was 180 per 1 million people, which compares favorably to the national rate of 268 per 1 million. However, individuals have to undergo rigorous screening to become donors, raising the question of whether the general population is an adequate control group for comparison.
Although living kidney donation is considered relatively safe, long-term risks of living kidney donation remain unclear. Even more concerning is the slow shift in demographics of the average living donor. The average age of living donors has increased with time. In 1998, 13.9% of donors were aged 50 years or older compared with 22.8% in 2008.4 In addition, obesity within the donor population has also increased. In 2000, 17% of donors were obese; this percentage rose to 21% in 2007.23
In addition, some centers now accept select patients with hypertension for living kidney donation. In fact, in a recent review of kidney donors, up to 24% were found to be medically complex, which was defined as obese (BMI greater than 30 kg/m2), hypertensive, or having a GFR less than 60 mL/min /1.73 m2. 24 The increasing demand for living donors to fill the void between new potential kidney recipients and deceased kidney donors has caused more transplant centers to consider living donors with isolated medical abnormalities (IMA) as potential donors. These are people who would likely have been turned down as living donors one or two decades ago.
However, long-term outcome data for donors with IMAs are lacking.25 Clearly, there is a critical need for better and larger studies reviewing long-term outcomes for living kidney donors. The creation of a national database to study outcomes of living kidney donors would be a large step forward in that direction. As physicians, we all take the Hippocratic oath and pledge to first and foremost cause no harm to our patients, but in this case, do we really know?
Dr. Hofmann is Associate Professor of Nephrology at the University of Wisconsin in Madison.
- Schweitzer EJ, Wiland A, Evans, D, et al. The shrinking renal replacement therapy “break-even” point. Transplantation. 1998;66:1702-1708.
- Mjøen G, Øyen O, Holdaas H, et al. Morbidity and mortality in 1022 consecutive living donor nephrectomies: benefits of a living donor registry. Transplantation. 2009;881273-1279.
- Najarian JS, Chavers BM, McHugh LE, Matas AJ. 20 years or more of follow-up of living kidney donors. Lancet. 1992;340:807-810.
- Segev DL, Muzaale AD, Caffo BS, et al. Perioperative mortality and long-term survival following live kidney donation. JAMA. 2010;303:959-966.
- Fehrman-Ekholm I, Elinder CG, Stenbeck M, et al. Kidney donors live longer. Transplantation. 1997;64:976-978.
- Eberhard OK, Kliem V, Offner G, et al. Assessment of long-term risks for living related kidney donors by 24-h blood pressure monitoring and testing for microalbuminuria. ClinTransplant. 1997;11(5 Pt 1):415-419.
- Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. N Engl J Med. 2009;360:459-469.
- Gracida C, Espinoza R, Cedillo U, Cancino J. Kidney transplantation with living donors: nine years of follow-up of 628 living donors. Transplant Proc. 2003; 35: 946-947.
- Saran R, Marshall SM, Madsen R, et al. Long-term follow-up of kidney donors: a longitudinal study. Nephrol Dial Transplant. 1997;12:1615-1621.
- Kasiske BL, Ma JZ, Louis TA, Swan SK. Long-term effects of reduced renal mass in humans. Kidney Int. 1995;48:814-819.
- Gossmann J, Wilhelm A, Kachel HG, et al. Long-term consequences of live kidney donation follow-up in 93% of living kidney donors in a single transplant center. Am J Transplant. 2005;5:2417-2424.
- Williams SL, Oler J, Jorkasky DK. Long-term renal function in kidney donors: a comparison of donors and their siblings. Ann Intern Med. 1986;105:1-8.
- Boudville N, Prasad GV, Knoll G, et al. Meta-analysis: risk for hypertension in living kidney donors. Ann Intern Med. 2006;145:185-196.
- Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.
- Textor SC, Taler SJ, Driscoll N, et al. Blood pressure and renal function after kidney donation from hypertensive living donors. Transplantation. 2004;78:276-282.
- Hemmelgarn BR, Manns BJ, Lloyd A, et al. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010;303:423-429.
- Garg AX, Muirhead N, Knoll G, et al. Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression. Kidney Int. 2006;70:1801-1810.
- Beekman GM, van Dorp WT, van Es LA, et al. Analysis of donor selection procedure in 139 living-related kidney donors and follow-up results for donors and recipients. Nephrol Dial Transplant. 1994;9:163-168.
- Poggio ED, Rule AD, Tanchanco R, et al. Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors. Kidney Int. 2009;75:1079-1087.
- Nogueira JM, Weir MR, Jacobs S, et al. A study of renal outcomes in African American living kidney donors. Transplantation. 2009;88:1371-1376.
- Pereira RB, Scheeren J, Castro D, et al. Follow-up of kidney donors who developed uremia and went on the waiting list for a transplant: should they have allocation priority? Transplant Proc. 2008;40:1012-1013.
- Gibney EM, Parikh CR, Garg AX. Age, gender, race, and associations with kidney failure following living kidney donation. Transplant Proc. 2008;40:1337-1340.
- Davis CL. Living kidney donors: current state of affairs. Adv Chronic Kidney Dis. 2009;16:242-249.
- Reese PP, Feldman HI, McBride MA, et al. Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers. Am J Transplant. 2008;8:2062-2070.
- Young A, Storsley L, Garg AX, et al. Health outcomes for living kidney donors with isolated medical abnormalities: a systematic review. Am J Transplant. 2008; 8:1878-1890.