Understanding Chronic Kidney Disease of Surgical Versus Medical Origin: The Missing Link to the Partial Versus Radical Nephrectomy Debate?

Abstract

In the USA and Europe, nephron-sparing surgery (NSS) has become accepted as the gold standard for renal masses of 4 cm in size [1,2]. There is general consensus in the urologic community that the acceptable increase in perioperative surgical risk inherent to partial nephrectomy (PN) is justified by the theoretical benefit of avoiding the long-term deleterious renal functional consequences associated with radical nephrectomy (RN). Concerns regarding adverse events associated with a decline in glomerular filtration rate (GFR) [3], such as cardiovascular compromise, chronic anemia, bone demineralization, and metabolic disturbances, have resulted in the intuitive and widely embraced hypothesis that NSS may result in a survival advantage when comparing PN and RN. Enthusiasm for NSS was fueled by observational studies demonstrating large differences in overall survival favoring PN [4,5], and PN rates have accordingly increased over the past decade [6]. Because of robust evidence of the oncologic efficacy of nephron-sparing excision of tumors of <5 cm [7], the indications for PN have expanded to include cT1b and cT2 lesions when technically feasible. However, momentum for the decision to perform PN in all amenable cases has been tempered by the results of European Organisation for Research and Treatment of Cancer (EORTC) trial 30904, which demonstrated an unanticipated survival advantage for RN [7]. The limitations of this study—early cessation because of failure to accrue and p values bordering statistical insignificance—have been cited as reasonswhy these data have largely been dismissed bymany kidney surgeons.With accumulating evidence that PN for renal masses of greater anatomic complexity is associated with higher perioperative risk [8] and that oncologic safety data for NSS for cT1b–2 tumors are lacking, preservation of a favorable risk/benefit ratio for complex PN versus RN for patients with a normal contralateral kidney remains contentious. It is indisputable that PN results in preserved renal function compared to RN [9]. However, the relationship between a surgically induced decline in GFR and overall health remains controversial, and clarification of this relationship will help us to understandwhy a demonstrable survival benefit was not observed for PN in EORTC 30904. In 2013, Lane et al [10] proposed that chronic kidney disease (CKD) resulting from surgical removal of nephrons (CKD-S) may be associated with a lower risk of CKD progression and improved overall survival when compared to CKD of medical etiology (CKD-M). While thought-provoking, this initial work was limited by a lack of data on cause of death and follow-up duration. In this issue of European Urology, Lane and colleagues [11] expand on their initial study by reporting extended follow-up of the impact of CKD-S on renal function, overall survival, and cause-specific survival in comparison to patients with CKD-M and those with no CKD. By retrospectively examining their institutional registry, the investigators were able to identify 2350 patients who developed CKD (GFR <60 ml/min/1.73 m) postoperatively from 1998 to 2008. Patients with postoperative CKD were further stratified into those with an estimated GFR <60 ml/min/1.73 m noted only after surgery (CKD-S) and EU RO P E AN URO LOG Y 6 8 ( 2 0 1 5 ) 1 0 0 4 – 1 0 0 6