Investigation of the Vulnerability of the Remaining Kidney Postunilateral Nephrectomy under Crystalline Nephropathy Conditions

Background: The loss of a kidney is a common outcome of single kidney transplantation, renal trauma, and renal cancer. Despite many studies showing stable function after unilateral nephrectomy (UNx), it can lead to overload of the remaining kidney. This overload may become a relevant factor in the development of Acute Kidney Injury and increase the vulnerability of the remaining kidney to Chronic Kidney Disease (CKD). Therefore, the present study aims to investigate the function of the remaining kidney after UNx, its response to crystalline nephropathy, and the potential factors and mechanisms involved in its vulnerability state. Methods: Eight-week-old male C57BL/6J mice (n=23) were divided into four groups: sham, subjected to UNx, sodium oxalate (intraperitoneal injection of 9 mg/100 g of NaOx to induce crystalline nephropathy), and UNx treated with sodium oxalate (UNx/NaOx). Six days after the sham or UNx surgery and twenty-four hours before the euthanasia, mice were treated according to their group and placed in metabolic cages for metabolic parameters and kidney function track. At the end of twenty-four hours, the animals underwent isoflurane anesthesia (0.8 L/min/rate 5%), blood and urine collection, removal of the left kidney and euthanasia by exsanguination. Results: One week after the surgery, the UNx animals showed a significant increase in urinary flow (p< 0,04), kidney weight/body weight ratio (p<0,003) and in plasma creatinine(p<0,004) when compared to sham animals. They also showed a significant increase in mRNA expression for Mki-67 (p<0,02), a biomarker to measure tubular regeneration and renal repair. Still in this group, we observed an increase in mRNA expression for Col1a1(p<0,05) and Col4a1(p<0,05) and in the protein expression of a specific macrophage marker, F4/80(p<0,004). Faced with NaOx insult, UNx/NaOx animals showed more pronounced renal hypertrophy (p<0,02), greater accumulation of creatinine in plasma (p<0,003) and greater expression of mRNA for tubular injury factors such as Havcr1 (Kim-1) (p<0,006) and LCN2 (NGAL) (p<0,0006) and protein expression of Kim-1(p<0,003), when compared to NaOx animals. Conclusion: Our findings indicate that the remaining kidney has vulnerability, which affected its response to the insult, and can potentially hindering improvement and contributing to the development of CKD. Funding: Government Support – Non-U.S.