(UroToday.com) In a podium presentation in the ESU-ESOU-ERUS session at the 19th Meeting of the EAU Section of Oncological Urology, Dr. Andrea Minervini discussed functional results following partial nephrectomy. He began by emphasizing that the goal of nephron sparing surgery is to provide an oncologically rigorous operation with low perioperative morbidity and limited renal functional damage.
In the evolution of nephron sparing surgical approaches, the initial focus was on oncologic outcomes and equivalence. However, he emphasized that longer-term functional outcomes should deserve equal attention, as has happened over time. In terms of renal functional outcomes, he emphasized the importance of both short-term acute kidney injury (AKI) and longer-term chronic kidney disease (CKD).
First focusing on AKI, he defined this as a rapid decrease of renal function (within 12-24 hours) due to impairment of nephrocyte function leading to fluid and catabolic waste retention with the potential for electrolyte and acid-base disturbances. There are a variety of criteria that may be used to assess AKI, including the KDIGO clinical practice guidelines, the RIFLE criteria, and the AKIN criteria.
There are a number of technical considerations which may contribute to the risk of immediate postoperative acute kidney injury. Most notably, the use of an enucleating approach, compared to enucleoresection or formal resection, was associated with a decreased risk of AKI. Further, the technique of renography may contribute to renal dysfunction: the use of a single-layer approach decreased the degree of decline in early postoperative renal function compared to a standard two-layer approach. In addition to these factors, for years, the duration of ischemia has been considered the greatest determinant of AKI. However, Dr. Minervini emphasized that a growing body of literature suggests that the quality of kidney is probably more important than ischemia time: patients with functionally normal kidneys can well tolerate prolonged warm ischemia. Thus, unmodifiable patient-related factors play a large part in determining the short- and long-term renal functional loss associated with partial nephrectomy.
Using comorbid characteristics including cardiovascular disease, diabetes, obesity, metabolic syndrome which may correlate with “kidney quality”, patients can be defined as low- and high-risk with respect to their likelihood of post-operative AKI on the basis of their comorbidities. This risk categorization was strongly associated with the effect of ischemia. Among patients at low baseline risk, warm ischemia of <10 minutes was associated with a 13% risk of AKI and those with warm ischemia of >20 minutes had a 28% risk. While the relative effect is similar, the absolute magnitude is much larger among those at high baseline risk: 31% among those with warm ischemia <10 minutes and 77% in those with warm ischemia > 20 minutes.
Acute kidney injury may have important consequences. While AKI was observed in 4.9% of patients, it was associated with increased in-hospital mortality, increased postoperative complications, increased transfusion rates, increased likelihood of prolonged hospitalizations, increased risk of hemodialysis, and increased risk of chronic kidney disease.
This highlights that there is a key interplay between AKI and chronic kidney disease. Thus, the initial functional damage associated with acute kidney injury is not entirely reversible. A maladaptive response of hyperfiltration, rather than regeneration, that leads to improvements over time in post-operative eGFR ultimately leads to premature cell senescence. This interplay is highlighted by data on nearly 2000 patients which showed that initial postoperative AKI was associated with a higher rate of CKD upstaging and that the duration of AKI was also associated with this longer-term risk.
Additionally, citing mouse data, Dr. Minervini highlighted that AKI may be associated with the development of papillary RCC, through an adenoma-carcinoma sequence of carcinogenesis.
Moving forward with discussion of the risks of CKD, he emphasized that it is associated with an increased risk of cardiovascular events, an increased risk of infective disease, and an increased risk of overall mortality. However, there is consistent evidence that, compared to radical nephrectomy, partial nephrectomy is associated with a reduced risk of de novo CKD and of CKD progression.