Biochemical and radionuclide monitoring of single kidney function in patients with metastatic renal cell carcinoma in the setting of immunotherapy

Sayapina M.S., Averinova S.G., Zaharova T.V., Kashkadaeva A.V., Shiryaev S.V., Poluektova M.V., Vorob'eva O.A.

Study objective: to study the effectiveness of complex monitoring of the kidney function, based on biochemical and radionuclide (RN) methods; to assess the diagnostic value of biomarkers of chronic kidney disease (CKD) at an early stage, to determine their association with RN parameters and efficacy of immunotherapy in patients with metastatic renal cell carcinoma (mRCC).

Materials and methods: this study included 41 mRCC patients after nephrectomy within the period from 2015 to 2017. 18 patients were treated with interferon (IFN-а), 23 patients were treated with nivolumab (as part of the Bristol-Myers Squibb (BMS) expanded access program). The median age was 56 years. Before the initiation of treatment and 2 months after, all patients underwent blood chemistry, urinalysis, Rehberg test and ELISA to determine serum levels of IL-17, TGF-в, and erythropoietin. The monitoring of the renal function and urodynamics by complex renal scintigraphy (CRS) was used for all patients using a dual-detector gamma camera and simultaneous data recording in 2 projections. 74 MBq of 99mTc-technephore, a Russian product from the bisphosphonates group, having glomerulotropic properties, was intravenously administered. The effective equivalent dose for CRS was minimal, - 0,6 mSv. The interpretation of CRS data used a concentration-rate model of urinary excretion and the original SENS CRS technology.

Study results: the incidence of stage-3 CKD at the time of the treatment was 35% in the nivolumab group and 17% in the IFN-а group. End-stage renal disease that required dialysis during immunotherapy was documented in 1 patient (2.4%). Statistically significant correlations were established between biochemical parameters with inclusion of IL-17, TGF-в, and RN, -D, excretion rate of 99mTc-technephore from the parenchyma and Rnfsс, a stable sign of nephrosclerosis (presumably, sclerosis of interlobar renal arteries), respectively. A significant correlation was established between the parameters of the complex functional monitoring with the prognosis for the risk of renal failure (RF) and efficacy of immunotherapy in mRCC.

Conclusions: patients with mRCC with better kidney function parameters have a better prognosis regarding the effectiveness of immunotherapy. All mRCC patients after nephrectomy were recommended, prior to the treatment initiation, to undergo biochemical monitoring with inclusion of TGF-P1 and IL-17, as well as radionuclide monitoring (CRS) to determine the RF risk at an early stage and to establish the prognosis for the underlying disease and timely adjust the treatment in order to improve their response to immunotherapy.

Authors declare lack of the possible conflicts of interests.

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metastatic renal cell carcinoma, immunotherapy, chronic kidney disease, complex renography, IL-17, TGF-b1