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Aim. To elucidate the safety profile and symptom-modifying effect of Аlflutop and diacerein in the treatment of Kellgren—Lawrence Stages II—III knee osteoarthrosis (OA) in patients with oxalate nephropathy and Stages I—II chronic kidney disease (CKD) and to refine the effect of these drugs on urinary syndrome and renal function as compared to a response to nonsteroidal anti-inflammatory drugs — cyclooxygenase inhibitors (diclofenac). Subjects and methods. This open-label comparative randomized trial enrolled 86 female patients with Kellgren—Lawrence Stages II—III primary gonarthritis concurrent with oxalate nephropathy and Stages I—II CKD. The patients were randomized into 3 groups: 1) 20 patients took diclofenac sodium 100 mg/day; 2) 30 received a complex pharmaceutical on the basis of glycozaminoglycans Аlflutop injection 1 ml per day for 20 days, then 2 ml intraartricular twice weekly in the following month; 3) 36 had diacerein (diaflex, «Rompharm Company») in a dose of 50 mg twice daily for 3 months. On day 30 and day 90 of treatment, the symptom-modifying effect was evaluated from changes in the joint pain and morning stiffness domains of the WOMAC index. Renal function was measured using the estimated glomerular filtration rate (GFR), uric acid clearance (Cua), and urinary sediment. Results. On day 30 of treatment, the patients taking diclofenac were found to have nephrotoxic effects (lower GFR, Cua, evolving secondary hyperuricemia, progressive proteinuria, emerging microhematuria, elevated urinary levels of total lipid hydroperoxides, and enhanced calcium oxalate crystalluria). Alflutop and diacerein exerted no negative effects on renal function. On day 30 day of treatment, all the patient groups showed a reduction in the WOMAC pain score. The diclofenac group displayed a more marked decrease in the pain score than did the two other groups by day 30. Otherwise by day 90 of therapy with Аlflutop and diacerein, the pain scores were reduced by 60 and 67%, respectively, which was similar to those in the diclofenac group by day 30 of a follow-up. By day 30 day of treatment, the stiffness score was also observed to fall in all the groups and achieved even lower values in the Аlflutop and diacerein groups compared with diclofenac group.. Conclusion. Alflutop and diacerein used by patients with knee OA do not produce nephrotoxic effects and by day 90 demonstrated similar to diclofenac symptom-modifying effect by reducing pain and stiffness scores. Diclofenac administration contributed to oxalate nephropathy progress.