Factors related to suboptimal recovery of renal function after living donor nephrectomy: a retrospective study

End-stage renal disease (ESRD) substantially increases the risk of death and cardiovascular disease [1‐4]. Renal transplantation is the best treatment option for ESRD [5]. In Japan, due to the shortage of deceased donors, 89.2% of renal transplants are from living donors [6]. To minimize the risk of ESRD after donation, the selection of living donors requires great care [7].

The renal function of the remaining kidney in living donors usually recovers up to 60~70% of baseline function through a compensatory hypertrophy mechanism [8, 9]. However, the degree of this compensatory hypertrophy varies from donor-to-donor. The reason for this between-donor difference is unclear; however, considering the wide range of the health status among living donors, the presence of subtle metabolic syndromes or preclinical renal diseases prior to transplantation are possible, [5] which could affect functional renal recovery after the donation.

Despite meticulous efforts to avoid adverse events for living donors, the 15-year risk of ESRD in donors is 3.5 to 5.3 times higher than that of a matched population [10, 11]. Therefore, accurate estimation of the residual glomerular filtration rate (eGFR) is crucial in order to maintain a donor’s life-long renal function and to prevent cardiovascular events.

We hypothesized that donors’ baseline characteristics and findings on baseline renal biopsy would predict the extent of compensatory hypertrophy after renal donation [5, 10]. Therefore, our aim in this study was to identify the factors related to a suboptimal recovery of renal function in living donors after donation.

We identified that hyperuricemia and chronic pathological changes (1 h after biopsy) are independent risk factors for suboptimal compensatory hypertrophy. Although pre-donation eGFRs were not different between the optimal and suboptimal groups, post-donation eGFR was nearly 10 ml/min/1.73m² lower in the suboptimal group in contrast to that in the optimal group.

We defined suboptimal compensatory hypertrophy at 1-year post-donation by an eGFR < 60% from baseline, based on the findings of Colin et al. [8] who reported that renal function after donation recovered to about 62.5~67% of baseline values, which is consistent with the findings in other studies [8, 9, 17, 18]. In addition, the rate of GFR decline was significantly higher in patients with a baseline GFR < 50 ml/min/1.73m² [2, 19, 20]. The risk of cardiovascular events and uremic symptoms significantly increased in patients with an eGFR < 45 ml/min/1.73m², [3, 20] with this risk increasing from 13 to 51%, for an eGFR range of 7.5 to 15 ml/min/m at 1 year [21]. Thus, by setting the cut-off at 60%, we were able to differentiate donors close to chronic kidney disease (CKD) stage IIIA (45~59 ml/min/1.73m²) from those with CKD stage IIIB (30~44 ml/min/1.73m²), which allowed us to identify the clinically relevant risk factors for suboptimal compensatory hypertrophy.

Interstitial fibrosis and tubular atrophy (IFTA) on baseline biopsy are more closely associated with lower long-term renal function in living donors than other abnormalities, including glomerulosclerosis and arteriolar hyalinosis [10]. However, IFTA is a pattern of injury that has many underlying causes, [22] which is why, in our study, we strived to specify the cause of IFTA by combining ct/ci and ah scores, which identified chronic ischemia induced by arteriosclerosis as the main cause of IFTA. Interestingly, the impact of this combination was independent of age, which is suggestive of a discrepancy between actual and biological age. Moreover, there was no correlation between chronicity score (ah≧1 ∩ ct + ci≧1) and glomerular atrophy. This result was consistent with the well-known fact that tubular atrophy is superior to glomerular pathology as a predictor of declining renal function [23].

It is impractical to obtain a baseline renal biopsy specimen as a component of the primary donor selection process. Instead, Ohashi et al. [5] showed that metabolic syndrome in donors is associated with chronic histological changes in the kidney and subsequent protracted recovery of kidney function after donation. In our study, hypertension, hyperlipidemia, and BMI were not significantly different between the two groups. Furthermore, HbA1c tended to be higher in the suboptimal group, but was not retained as an independent predictor on multivariate analysis. This may be due to the small number of donors. However, uric acid was an independent risk factor for suboptimal recovery of donor renal function. Although the uric acid levels of both groups were in the normal range in our study, this result suggests that higher uric acid levels may be related to the suboptimal recovery of renal function after nephrectomy. Iseki et al. [24] reported a decline in eGFR of 1.91 ~ 4.19 ml/min/1.73m² per 1-mg/dl increment in uric acid, indicative of a role of uric acid in CKD progression. The OR for CKD of 1.4 (95% CI, 1.1~1.8) per 1-mg/dl increment in uric acid, which does not conflict with previous findings by Ficociello et al. [25], who demonstrated a significant association between uric acid and the development of early GFR loss. Sumiyoshi et al. [26] and Nagahama et al. [15] reported that higher uric acid levels were independently associated with a greater risk of incident metabolic syndrome and that hyperuricemia tends to have a clustering of cardiovascular risk factors. In addition, Antonini et al. [27] showed that carotid arterial stiffness is related to uric acid, independently of established cardiovascular risk factors. Although pre-donation hyperuricemia is not included in the donor evaluation guidelines [7], caution should be exerted when hyperuricemia is detected in a donor, regardless of normal renal function.

Some limitations of our study were that it was a single-institution study with a small sample size; further, analysis was retrospective in nature and the follow-up term was relatively short. As biopsies are difficult to perform prior to donor selection, these findings cannot be included in the donor selection process. Additional studies are needed to investigate the added contribution of other factors to the health status of donors, such as pre-sarcopenia, to predict chronic renal pathology from clinical findings.

Pathological findings in biopsy specimen at 1 h and higher uric acid level were associated with insufficient recovery of renal function at 1 year after donation. Living donors with hyperuricemia and a high chronicity score (ah≧1 ∩ ct + ci≧1) should be followed up with caution after donation.