The demographics of our cohort are similar to that of previous studies in terms of age, gender (10–14, 18–20), mean follow up period 7.5 to 10 years (5, 11–14, 19, 20), prevalence of hypertension and diabetes (10–12, 14, 19, 20), indication for RC bladder cancer (10–12, 14, 18, 19), with stages T ≥ 2 from 63 to 78% (12, 19, 20), therefore, our study is comparable to these previous reports.
We found that the majority experienced a decrease in renal function during long-term follow up. The initial eGFR in our cohort was 65.8 ml/min/1.73 m2, which is similar to previous reports (10, 12–14, 19) with initial eGFR ranging from 65 to 69.7 ml/min, with the exception of Samuel et al, that show an eGFR of 77, most likely because of a younger population group. The eGFR after two years was 55 ml/min, again similar to previous reports with ranges from 55 to 59 (11–14, 19), being comparable. 62.8% of patients had a decline of their kidney function during follow up, and 32.8% of patients had a decrease of > 10 ml/min/1.73 m2 at 2 years. Previous studies have shown a high prevalence 70% (11, 20) at 10 years, and 49% at 5 years (11), however there are reports with a lower prevalence 34 to 51% (12–15). The difference in the prevalence through the different studies could be explained due to different definitions to categorize the decline in kidney function, as well as different follow up times, and different methods to measure the GFR.
There is a predictable decline in the kidney function related to aging; the annual age-related decline in eGFR from age 30 years is believed to be ± 1 mL/min/1.73 m2 in healthy population (21–23), this GFR declines by about 8–10 ml/min/1.73 m2 per decade (24, 25), by other side, a linear decline in eGFR over time is often observed (26) in patients with diabetes or HTN, the decline in persons with diabetes range from ± 2–3 mL/min/1.73 m2 per year (27). In patients with RC and ICD, previous reports have used definitions such as a decrease of 1 ml/min/year (5, 11, 12) in a time period of 5 to 10 years, a decrease of > 25% (15, 19) in eGFR from baseline, or a decline > 10% in eGFR (11, 14). The definition of clinical significant deterioration in renal function in our study was a decrease of > 10 ml/min/1.73 m2 in the first two years. This was selected because the majority of the observed decline in kidney function in previous studies happens in the first 2 years (12, 19). This represents the period for major risk for kidney function deterioration, which is likely associated with RC and of clinical significance.
A further difference relates to the method used to measure the kidney function in patients with RC. The most common methods used are the MDRD (12, 14, 18), CKD-EPI (10, 11) and isotopic (5, 18) methods. These equations represent a practical way to measure kidney function, which is reliable, easy to use and reproducible. The gold standard to measure the GFR is the use of isotopes or inulin; these methods are costly and not widely available in clinical practice. There are reports that suggest that methods like MDRD and CKD-EPI overestimate the GFR comparing this with isotopic methods (18) in patients post RC. Therefore, the differences between these series can be explained by variations in patient selection and the variety of methods used to calculate the eGFR.
The use estimated methods to assess the kidney function have some caveats and considerations. One important consideration is that these equations are dependent of the level of creatinine; this can be modified for a decreased or increase in the kidney function, but can also be affected by muscle mass, weight, diet, exercise and other possible factors (28, 29). A decrease in weight after diagnosis of cancer is a frequent phenomenon, Meyerhardt et al, previously reported a decrease in 37.5% of patients (30). On the other hand, it is unclear whether there is significant reabsorption of urea and creatinine in ICD patients, as the contact time of urine is shorter and the reabsorbing surface of an ICD is small. Animal models suggest that much of the creatinine is reabsorbed by solvent drag, a glucose-dependent way of transport. Creatinine is reabsorbed less well by an active carrier mediated transport. As urine normally does not have large amounts of glucose, creatinine may be resorbed to a lesser degree (31).
It should be noted that changes in renal function were not uniform across patients, in our analysis we showed that 36.7% of our patients has stable or mild increase in their eGFR, and 10.6% an increase > 10%, previous reports showed similar findings Rouanne (12) et al 26%, Gondo (10) et al 56%. The presence of urinary obstruction (5) clinical or subclinical can affect the kidney function, therefore, once release of the ureteral obstruction happen after the RC, the kidney function will often improve (5, 10).
Our study showed cumulative incidence of dialysis of 5.6% at 5 years; Jin et al (14), report only 1.2% and Rouanne (12) et al 2.5%. The low incidence in the Jin (14) et al report may be related to a younger population patient selection, exclusion criteria. Additionally, the incidence of dialysis may be affected by high mortality; also, because there is a higher incidence of comorbidity, the decision for conservative treatment may have been made.
The long-term renal function after RC can be adversely affected by several factors, including age, potential nephrotoxic chemotherapy, comorbidities, and diversion-related factors. Our results are concordant with previous studies, in that age and preoperative eGFR are associated significantly with postoperative renal function on both univariate and multivariate analyses (11, 12, 32). However, there is not a clear consensus about other risk factors; neither chronic hypertension nor diabetes mellitus were associated with the decline eGFR (10, 12, 19, 32), or different types of ureterointestinal anastomoses, such as Bricker versus Wallace (12, 32) and urinary infection (12), chemotherapy (19, 32); nonetheless, other reports have shown association with HTN (5, 11, 14), Diabetes (14), hydronephrosis post RC (11), urinary infection (5, 11, 14) or total subcutaneous fat (10).
The mortality at 10 years in the different cohorts was from 59 to 65% (12, 14) in our study was 76.5%. After adjustment in multivariate analysis the main risk factors associated were age, eGFR pre operative and sex. The lack of association with previous well-known risk factors like HTN or DM are most likely related to the follow up, the nature of the cancer and a high mortality rate, that have a high impact as a competitive event.
The present study is limited by its retrospective nature, nonrandomized design and it single institution study design may be associated with unknown biases. Additionally, we could not include well-known other clinical factors such as nutrition condition due to unavailability of data; excluding who did not have complete data available may have introduced selection bias. Despite these limitations, we have analysed a significant number of patients, with regular follow up, and we confirmed the live status, mortality and dialysis status with the National Cancer Centre Office and the National Renal Registry databases which are regularly updated and maintained prospectively. We did not evaluate the gold standard measures of inulin clearance or use of isotopes, we recognize the potentially limited accuracy of measuring serum creatinine in our patients, but the use of the eGFR is the common general practice, due to simplicity, cost and availability, and the eGFR is mainly used for management and therapeutic approach in practice.