Incidence of RCC in a transplanted kidney
Among all patients who underwent kidney transplant and were monitored at the Moscow City Nephrology Center, the proportion of adult men was 57.52% (1881 people), while the female proportion was 42.48% (1389 people). The age of the patients ranged from 18 to 84 years, with an average of 41.3 ± 12.5 years. It is also worth noting that among patients with verified cancer of a transplanted kidney, the proportion of men was 51.6% (16 people), and women − 48.4% (15 people). The age distribution of patients with RCC allograft was predominantly within the range of 26 to 69 years, with an average age of 51.8 ± 8.5 years.
The overall incidence of renal cell carcinoma (RCC) in kidney transplants was 0.95%. The time from transplantation to RCC development ranged from 2 to 25 years, with an average of 8.4 years. Pathomorphological examinations revealed clear-cell RCC in 20 patients (64.5%) and papillary RCC in 11 patients (34.5%). The average time to the development of clear-cell RCC was 9.9 years, compared to 5.5 years for papillary RCC.
Surgical treatment of RCC in transplanted kidney
The surgical treatment was performed in 29 patients (94%): 28 patients underwent laparoscopic organ-preserving resection of the neoplasm-bearing kidney graft, one patient underwent laparoscopic transplantectomy due to extensive tumor involvement. The median duration of surgical intervention in the patient group with intraoperative minimally invasive ultrasound navigation was 135 minutes (117.5–144 minutes), compared to 123 minutes (112.5-144.5 minutes) in the group without navigation. The median ischemia time was significantly lower in the ultrasound guidance group at 24 minutes (20–25 minutes) versus 29 minutes (24–32 minutes) in the group without additional imaging (p < 0.05). Intraoperative blood loss ranged from 50 to 500 ml, and averaged approximately 162 ml. After laparoscopic resection of the transplanted kidney with the tumor, all patients experienced maintained function of the kidney transplant, despite a transient increase in serum nitrogenous base levels and a reduction in urine output. Specifically, the average serum creatinine level prior to surgical treatment and 12–18 hours post-laparoscopic resection were 187.1 µmol/L and 232.4 µmol/L, respectively (p < 0.05). A decrease in average creatinine levels to nearly preoperative values was observed on postoperative day 6 and 7, reaching 192.5 µmol/L.
Genetic insights.
The extraction of DNA from paraffin-embedded blocks of tumor and transplanted kidney tissue, obtained at post-histological examination, was successful in only 11 out of 31 patients. A 100% match was observed between the DNA markers of the transplanted kidney tumor and the DNA from the unaffected transplanted kidney tissue. A study of the VHL gene in the context of clear-cell RCC in transplanted kidneys was possible in 7 tissue samples. Mutations in the exons of VHL gene were identified in 5 of these samples (71.4%). Specifically, a c.221_222 TC > AT substitution in exon 1 of the VHL gene was detected, leading to a p.Val74Asp amino acid substitution (Fig. 1).
Deletion of c.470_473delCTCT (p.Thr157Arg*fs12) was found in exon 3 of the VHL gene, resulting in a frameshift mutation. This alteration leads to the substitution of the C-terminal peptide with a different amino acid sequence and the premature introduction of a stop codon. (Fig. 2).
The identification of VHL gene mutations in the tumor DNA, corresponding to the donor genotype, established that the cancer in the transplanted kidney originated from an inherent genetic predisposition of the transplant's renal parenchyma, i.e. the donor tissue, to the development of RCC. Such predisposition was likely exacerbated by the continuous administration of immunosuppressive therapy.
The average time to RCC development in patients receiving tacrolimus as IST primary component was statistically shorter compared to those receiving cyclosporine, with median times of 5 years (3.8–6.3 years) and 14 years (8.5–16 years), respectively (p < 0.05).