[DEFERRED NEPHRECTOMY IN A PATIENT WITH METASTATIC RENAL CELL CARCINOMA AFTER A NEAR-COMPLETE RESPONSE TO IMMUNOTHERAPY].

INTRODUCTION: The treatment of newly diagnosed metastatic renal cell carcinoma (mRCC) evolved dramatically with the approval of immune checkpoint inhibitors (ICI) such as nivolumab, ipilimumab, and pembrolizumab for this indication. Herein, we describe the case of a 52-year old male patient, without chronic diseases and with a 30-pack-year smoking history, who was diagnosed with mRCC (clear cell carcinoma) including enlarged lymph nodes in the mediastinum, a mass in the pleura, and numerous metastases in both lungs. The patient was treated with a combination of nivolumab and ipilimumab, followed by nivolumab monotherapy, which is still ongoing (as of December 2021). The patient had a near-complete response (near resolution of the metastatic lesions) and did not experience adverse events. After 13 months of treatment, and in light of the near-complete response, the patient underwent a radical laparoscopic nephrectomy. The postoperative period was uneventful and the patient was discharged from the hospital 3 days after surgery. Examining the excised kidney revealed no residual tumor, connective tissue, signs of inflammation and necrosis. As of December 2021 (approximately 23 months from immunotherapy initiation) the patient had no evidence of disease. This case report demonstrates a treatment approach involving deferred nephrectomy after (and during) ICI treatment. The response of the patient described herein to a combination of nivolumab and ipilimumab is consistent with the available data supporting the efficacy of this combination as a first-line therapy in mRCC. Currently, the evidence supporting deferred nephrectomy (after ICI) vs upfront nephrectomy and then ICI, or ICI alone without nephrectomy is limited to a few retrospective studies. Thus, prospective randomized studies are needed to elucidate the role of deferred nephrectomy in mRCC. Two phase 3 studies (PROBE and NORDIC-SUN) that were designed to address this issue are currently enrolling patients and their results are expected within several years.

Successful Introduction of Human Renovascular Units into the Mammalian Kidney.

BACKGROUND: Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in in vivo formation of vascular networks. METHODS: We administered renal tubule-forming cells derived from human adult and fetal kidneys (previously shown to exert a functional effect in CKD mice) into mice, alongside MSCs and ECFCs. We then assessed whether this would result in generation of "renovascular units" comprising both vessels and tubules with potential interaction. RESULTS: Directly injecting vessel-forming cells and renal tubule-forming cells into the subcutaneous and subrenal capsular space resulted in self-organization of donor-derived vascular networks that connected to host vasculature, alongside renal tubules comprising tubular epithelia of different nephron segments. Vessels derived from MSCs and ECFCs augmented in vivo tubulogenesis by the renal tubule-forming cells. In vitro coculture experiments showed that MSCs and ECFCs induced self-renewal and genes associated with mesenchymal-epithelial transition in renal tubule-forming cells, indicating paracrine effects. Notably, after renal injury, renal tubule-forming cells and vessel-forming cells infused into the renal artery did not penetrate the renal vascular network to generate vessels; only administering them into the kidney parenchyma resulted in similar generation of human renovascular units in vivo. CONCLUSIONS: Combined cell therapy of vessel-forming cells and renal tubule-forming cells aimed at alleviating renal hypoxia and enhancing tubulogenesis holds promise as the basis for new renal regenerative therapies.