Objective: The aim of the study was to compare the treatment outcomes between suctioning flexible ureteroscopic lithotomy (SF-URL) with automatic control of renal pelvic pressure and minimally invasive percutaneous nephrolithotomy (MPCNL) for the management of 2–3-cm renal stones in patients with a solitary kidney. Materials and Methods: A total of 127 patients with a solitary kidney who underwent SF-URL (n = 57) or MPCNL (n = 70) for large renal stones (>2 cm) between June 2015 and October 2020 were consecutively analyzed. The stone characteristics, operative times, stone-free rate (SFR), hospital stays, and incidences of complications were compared. Results: There was a significantly shorter operative time with MPCNL than with SF-URL (43.4 ± 18.9 min vs. 61.8 ± 21.1 min, p = 0.012). SFR at 30 days were 80.7% (46/57) and 90.0% (63/70) for SF-URL and MPCNL, respectively (p > 0.05). The SFR at the 3-month follow-up was comparable in both groups (91.2% vs. 95.7%, p > 0.05). The hemoglobin decline value, hospital stay, serum cystatin C, and percentage of patients requiring blood transfusions in the SF-URL group were obviously better than those in the MPCNL group: (0.8 ± 0.4) versus (3.9 ± 2.7) g/dL (p = 0.007), (3.6 ± 1.5) versus (6.9 ± 3.1) days (p = 0.013), (1.02 ± 0.48) versus (2.54 ± 0.69) mg/L (p = 0.011), and 0 (0.0%) versus 7 (10.0%) (p = 0.016), respectively. The percentages of patients with thrombosis and perirenal hematoma in the MPCNL group were higher than those in the SF-URL group, but the difference was not statistically significant (p > 0.05). Conclusion: For the treatment of 2–3-cm renal stones in patients with a solitary kidney, both SF-URL and MPCNL are effective. MPCNL has the advantage of a shorter operation time. However, SF-URL is characterized by less bleeding, shorter hospital stay, and less damage to kidney function.

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