ABSTRACT
Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.
ABSTRACT
JC virus (JCV) is a member of polyomaviridae family that infects approximately 70% of the population worldwide. JCV constantly stays in a latent state after the primary infection. In immunosuppressed individuals, especially under the circumstances of low cellular immune function, JCV may be reactivated and lead to severe clinical manifestations. In recent years, the correlation between JCV and complications after renal transplantation has captivated widespread attention. JCV-associated nephropathy (JCVAN) has been reported. Here, latest research progresses on the epidemiology, molecular biology, in vivo infection process, JCV and complications after renal transplantation, and the relationship between JCV and BKV were reviewed, aiming to provide reference for the adjustment of immunosuppressive regimen following renal transplantation.
ABSTRACT
Objective To analyze the risk factors of high-level BK viruria after renal transplantation and the significance in preventing BK virus-associated nephropathy (BKVAN). Methods Clinical data of 262 renal transplant recipients with regular follow-up data were retrospectively analyzed. According to the DNA load of BK virus, all recipients were divided into the high-level BK viruria group (n=35) and non-high-level BK viruria group (n=227). The incidence of high-level BK viruria after renal transplantation was summarized. The risk factors of high-level BK viruria after renal transplantation were analyzed by univariate analysis and multivariate analysis. Survival curve was delineated by Kaplan-Meier method, and survival analysis of recipients was performed. Results Among 262 renal transplant recipients, 35 cases developed high-level BK viruria with an incidence of 13.4%. The median time of occurrence of high-level BK viruria was 181 (126, 315) d. The incidence was the highest within 6 months after renal transplantation, gradually decreased from 6 months to 2 years, and then increased after 2 years. Univariate analysis showed that the history of antithymocyte globulin (ATG) treatment, acute rejection (AR), donation type and delayed graft function (DGF) were the risk factors of high-level BK viruria after renal transplantation (all P < 0.05). Multivariate Cox regression analysis demonstrated that donation after brain death followed by cardiac death (DBCD), AR and DGF were the independent risk factors of high-level BK viruria after renal transplantation. The 1-, 3- and 5-year survival rates of recipients with ATG treatment history, AR, DGF and donation type of DBCD were significantly lower than those with non-ATG treatment history, non-AR, non-DGF and other donation types [donation after brain death (DBD), donation after cardiac death (DCD) and living organ donation] respectively (all P < 0.05). Conclusions DBCD, AR and DGF are the independent risk factors of high-level BK viruria after renal transplantation. Strengthening the postoperative monitoring of these recipients and delivering early intervention may effectively prevent BKVAN.
ABSTRACT
Objective BK virus-associated nephropathy ( BKVAN) after kidney transplantation is a key factor that influence the prognosis of transplant kidney .To our knowledge , it is believed to be associated with immune suppression .We observed the cura-tive effect and influencing factorsof anti-rejection scheme that Leflunomide was administered instead of Mycophenolate Mofetil ( MMF) on transplant kidney BKVAN .. Methods This study included 15 kidney transplant recipients with pathologically confirmed BKVAN in Nanjing General Hospital of Nanjing Military Region form March 2007 to March 2013 .Leflunomide was administered instead of Myco-phenolate Mofetil ( MMF) .Serum creatinine level , renal allograft loss rate and side effects of leflunomide were monitored after medica-tion switch.The patients were divided into two groups , which were renal allograft loss group and renal allograft survival group , for fur-ther analyses . The differences between each groups in clinical characteristics as well as histochemical features of the transplanted kidneys were analyzed to determine the cause of renal allograft loss in patients with BKVAN . Results Six patients experienced renal al-lograft loss after switching to leflunomide and needed hemodialysis , and 9 patients had stable renal allograft function , renal allograft loss rate was 40.0%.Hyperuricemia occurred in 8 patients in the period before the medication switch and in 5 patients after the switch;a decrease in blood white cell orplateletcount was found in 2 patients during both periods;an increase in Alanine aminotransferase ( ALT) level occurred in one patient after the medication switch .There were no statistically significant differences in any of the above parame-ters before and after the medication switch.Compared to allograft survival group, serum creatinine level[(1.80 ±0.53)mg/dL vs (2.74 ±0.58)mg/dL, P=0.007], the number of B lymphocytes [(206.44 ±144.96) vs (439.67 ±267.77), P=0.047] and CD68[(588.44 ±271.80) vs (944.67 ±259.32), P=0.025] in renal allograft tissue were significantly higherin the allograft loss group. ConclusionLeflunomide is a safe and effective medication for BKVAN .Patients with significantly increased serum creatinine level might have a poorer prognosis .Significantly increased B lymphocytes and CD 68 cells in renal allograft tissue might indicate a poor prognosis.