In the present study, the trend of eGFR levels increased from preoperative to over 2 years after radical nephrectomy, representing that CKD is a chronic condition. Both MetS and non-MetS groups showed recovery of eGFR postoperatively, however MetS patients demonstrated a significantly lower recovery rate. Also, at 24 months after radical nephrectomy, the severity of CKD in patients with MetS was higher than the severity in patients without MetS. Baseline eGFR level, hypertension and diabetes mellitus appear to be risk factors for moderate to severe CKD. Differences in renal pathological features between the two groups, including global sclerosis, tubular atrophy and interstitial fibrosis, which were all more prevalent in patients with MetS at the time of radical nephrectomy, indicating that MetS may cause more severe kidney injury. Overall, results of the present study confirm that patients with MetS need a longer time for renal function recovery after radical nephrectomy than those without MetS. It is also clear that MetS patients who underwent radical nephrectomy had greater risk of progression of renal insufficiency.
CKD following nephrectomy due to RCC will lead to ESKD or cardiovascular events, which is associated with potential cardiovascular and overall survival, also has a heavy impact on patients’ quality of life. Thus, predicting the risk of CKD before surgical management of RCC may be invaluable in helping patients and surgeons to determine the necessity of surgical treatment, and improve both the surgery and follow-up plans to balance the risk of oncological and renal function progression and achieve maximum benefit for the patients. For example, early referral to a nephrologist and initial regular eEGF monitoring and appropriate, timely management is essential. The patient population in the present study had all undergone radical nephrectomy, which is typical for those who have advanced RCC and are more likely to have preoperative CKD, and preservation of renal function is both more necessary and more difficult. The data of patients’ baseline characteristics also confirmed these factors.
CKD, regardless of the causes, and RCC share many risk factors, including age, gender, smoking, hypertension and diabetes mellitus, and these are also related to MetS components. In a large cohort study with nearly 1,200, 000 adults with eGFR< 30 ml/min/1.73 m2 and a two-fold risk of RCC compared to those with 60-89ml/min/1.73 m,28 CKD itself was reported to be an independent risk factor for RCC. In order to clarify the effects of MetS and simplify the study design, we controlled for age and gender. Also, because associations between the tumor size and surgical approach have been studied as well as the development of CKD after nephrectomy,[26, 28] we also adjusted for these factors in our analysis. However, this strategy limited the generalization of our results and is a limitation of the present study.
MetS is a combination of metabolic disorders. Even the MetS-related abnormalities such as hypertension and diabetes mellitus are shown to increase the risk of CKD after nephrectomy. Therefore, MS may reflect a more comprehensive presentation of individuals with CKD risk than each individual component of MS. When Kriegmair et al.12 evaluated the impact of MetS and each of the single components of MetS on outcomes of patients with RCC, the results of Kaplan-Meier and log-rank analysis revealed that MetS was significantly associated with a shorter PFS (p=0.018), whereas no significant differences were found in the effects of diabetes mellitus, BMI, hypertension and hypertriglyceridemia on the outcomes. Another study of the outcomes of patients with RCC had controversial results. Diabetes mellitus and hypertriglyceridemia were shown to be associated with worse PFS in RCC patients, [29, 30] but obesity had a positive impact on RCC outcomes. No consensus has yet been reached in previously published studies. The pathogenetic mechanisms of MetS for inducing diseases or influencing disease outcomes, including insulin resistance, inflammation, endothelial dysfunction, oxidative stress, or all of above, may lead to nephron injury and further renal function impairment. Thus, using MetS as a relatively comprehensive marker for CKD risk can probably identify CKD risk before it actually occurs.
In the present study, global sclerosis, tubular atrophy and interstitial fibrosis were seem more frequently in patients with MetS. Histopathological abnormalities identified in the non-neoplastic parenchyma of the kidney are associated with renal function decline after radical nephrectomy. These findings are consistent with the results reported by Alexander et al. In addition, obesity has been shown to induce glomerulosclerosis in an animal model, resulting in ESRD. Interstitial fibrosis and tubular atrophy are both related to hyperlipidemia-induced oxidative stress, the increased reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), which together increase the level of matrix synthesis and reduce matrix degradation, resulting in glomerular, tubular and vascular damage.[35, 36]
This study has several limitations, including its retrospective nature, which limits generalizations to other populations and precludes inferences of causation. It also had a small sample size from a single hospital. Further prospective study with a large multicenter cohort study would help to confirm results of the present study.
In conclusion, clinicians treating RCC patients with concomitant MetS should be aware of the possibility of decreasing eGFR and CKD progression more than in RCC patients without MetS after radical nephrectomy, and routine monitoring of renal function should be emphasized in the post-nephrectomy follow-up plan. A large prospective cohort study should be conducted to further support the findings of the present study.