The kidney presents a functional reserve capacity after unilateral nephrectomy [1,2]. Many studies reported that the donor’s global renal function decreased immediately after kidney donation . Although most of these studies compared the global GFR of the bilateral kidneys before donation with that of the single kidney preserved after nephrectomy , they did not compare the functional change of the same donor’s remnant and donated kidney in their new milieus after operation. The renal function of split kidneys from living donors can be monitored perioperatively in real world. In this study, we sought to measure the initial GFR of the split kidney and compare it with the kidney preserved and donated respectively, aiming to explore the potential compensation capacity of the split kidney from living donors.
Time and mechanism of the renal compensation phenomenon
Compensatory renal growth of the remnant kidney starts within hours following nephrectomy and reaches a stable compensatory state in varying periods post-operation. For human living kidney donation, GFR of donors and recipients was compensated and remained stable about one month after operation [6,7]. Gong et al. reported that donor’s mean GFR remained stable at (85.2±17.6) ml/(min·1.73 m2), (87.2±15.9) ml/(min·1.73m2), (82.1±14.6) ml/(min·1.73m2) and (83.0±13.7) ml/(min·1.73 m2) 5 days, 3 months, 1 year and more than one year after LKT respectively. Knowing that the GFR reached stability about one month after operation in most related studies [4-7], we used GFR at one month after operation as the main parameter for analysis.
Compensatory renal growth following nephrectomy is predominantly due to renal cell hypertrophy [1,8]. The mechanisms that sense and respond to renal volumetric reduction which generate renal growth remain elusive. Two main mechanisms have been proposed. One ascribes it to the increased activity of the remnant kidney that leads to hypertrophy, and the other attributes it to the release of kidney specific factors such as insulin-like growth factor 1, epidermal growth factor and hepatocyte growth factor and pathways such as mammalian target of rapamycin in response to unilateral nephrectomy [1,8].
GFR compensation capacity of the remnant kidney
Several studies have reported on the compensatory capacity of remnant kidneys after nephrectomy [2,4,9]. Chien et al. reported that GFR of donor’s remnant kidney compensated from 58.2 ml/(min·1.73m2) to 79.6 ml/(min·1.73m2), with a 36.9% increase in C-percentage . Our finding is consistent with the results from other centers in term of the tendency, indicating an acceptable and reasonable compensation in the remnant kidney. In our study, GFR in the remnant kidney averaged a 46.6% increase, which is better than 36.9% reported by Chien.
We also observed a case with the highest C-percentage in a 43-year-old father who donated the left kidney to his 22-year-old son. GFR of the father’s right kidney was 51.3 ml/(min·1.73 m2) before operation and increased to 107.0 ml/(min·1.73 m2) after operation, with a C-percentage of 108.6%, indicating that the remnant kidney of a healthy donor possesses a powerful compensation capacity after donation to meet the physiological needs of the donor.
Impact of donor’s age on renal function compensation
Serrano et al.  reported that donors in the optimal group were significantly younger, the optimal/suboptimal ratio being 56.0±10.4 vs. 60.7±8.7 years(p=0.018). Univariate analysis in our study showed a significantly higher GFR C-percentage of the remnant kidneys in younger donors ≤50 years than that in older donors (58.2% vs. 26.6% , p=0.005). The above results showed that the remnant kidneys of younger donors have higher compensation capabilities, which is in line with the natural psychological tendency that the renal function decreases with age in ordinary healthy people. However, it is interesting to find that there was no significant difference in the GFR compensation rate of the donated kidneys in the recipients’ bodies between the young and old donor age groups [67.9% (IQR=47.6-93.9%) vs. 67.8% (IQR=36.1-95.0%), p=0.675]. The reason may be that transplanted kidneys are affected by multiple factors in the new milieus of the recipients, such as immunological and hemodynamic factors, all of which may attenuate the impact of age on the grafts.
Preoperative assessment of nadir GFR for the kidney to be donated
The donated kidney has to adapt to the new milieu before it can gradually recover its function and compensatorily develop its infiltrating capacity in the recipient’s body. Further sub-group analysis of our study showed that among 12 donors with donated GFR < 40 ml/(min·1.73m2) before donation, the median GFR D-value was 30.4 ml/(min·1.73m2)(IQR=25.7-37.1ml/(min·1.73 m2)) and C percentage was 90.2%(IQR=67.8-127.4%). In the group with GFR of the donated kidneys ≥40 ml/(min·1.73m2) before donation, the median GFR D-value was 18.2ml/(min·1.73 m2)(IQR=6.8-28.1ml/(min·1.73 m2)) and C-percentage was 62.0% (38.4%-92.7%). This indicates that donated kidneys with a relatively low GFR before operation have an even more powerful compensatory capability because the donated kidney is fully compensated in the body of the recipient.
Currently, it is difficult to define the acceptable nadir GFR value of the kidney to be donated before operation. Most transplantation centers recommend ≥40 ml/(min·1.73 m2) as the cutoff value [3,11]. But as the compensation capability of the donated kidney is higher than that of the remnant kidney as shown in our study, donated kidneys with an estimated GFR value <40 ml/(min·1.73 m2) before operation can still be considered as potential candidates for donation. We suggest that the GFR criterion for kidney donation could be selectively reduced to 30 ml/(min·1.73 m2) in potential donors. Of course, the baseline GFR of the remnant kidney should be maintained at a ≥40 ml/(min·1.73 m2) level so as to guarantee that the donor’s remnant kidney has a good filtering function after nephrectomy .
Our study has some limitations. First, it is of retrospective nature with all data retrieved from a single center, which may bring about tertiary selection bias. In addition, sample is relative small due to the gradual application of LKD in our country. Therefore, further studies are required to focus on the compensatory growth after kidney donation.