Background: Chronic kidney disease (CKD) poses a significant global health challenge, affecting approximately 10% of the population. Patients with an acquired solitary kidney (ASK) from nephrectomy face elevated risks for CKD progression because of the increased functional demand on the remaining kidney. This study aims to identify risk factors for CKD progression in patients with a surgical ASK, highlighting the challenges faced by this population. Methods: This study retrospectively examined factors associated with renal function decline in 115 ASK patients who underwent nephrectomy for various pathologies, including renal tumours, urothelial tumours, and trauma. Follow-up assessments were conducted at 1, 12, 24, and 36 months post-nephrectomy, examining glomerular filtration rate (eGFR) and other renal function markers. Preoperative and postoperative data were analysed, with creatinine and eGFR measurements taken preoperatively, immediately postoperatively, and at all follow-up intervals. Results: The results of this study, which revealed that hypertension, diabetes mellitus, and preoperative kidney stones in the remaining kidney were significantly associated with accelerated CKD progression, with odds ratios of 2.7, 3.5, and 3.2, respectively, underscore the need for further research in this area. Although dyslipidaemia was observed in most patients (60%), its association with CKD risk did not reach statistical significance (p = 0.06). Conclusions: Our study highlights the critical need for ongoing urological assessment and tailored management strategies for patients with a solitary kidney following nephrectomy. By identifying key risk factors associated with renal function decline, we emphasise the importance of proactive monitoring and intervention to enhance long-term outcomes in this vulnerable population.