J. Fei

Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence, reduction in immunosuppression and clinical course

Huang G, Chen L‐Z, Qiu J, Wang C‐X, Fei J‐G, Deng S‐X, Li J, Chen G‐D, Zhang L, Fu Q, Zeng W‐T, Zhao D‐Q. Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence, reduction in immunosuppression and clinical course.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01141.x
© 2009 John Wiley & Sons A/S.

Tuberculosis in southern Chinese renal-transplant recipients.

Abstract: Objectives:  To analyze the characteristics of tuberculosis (TB) in Southern Chinese renal transplant recipients, and summarize the corresponding experiences in diagnosis and management.

Monitoring of polyomavirus BK replication and impact of preemptive immunosuppression reduction in renal-transplant recipients in China: a 5-year single-center analysis.

This provides the long-term patient/graft survival and outcome of BK viremia and BK virus allograft nephropathy (BKVAN) in renal transplant recipients in the setting of intensive monitoring and preemptive of reduction of immunosuppression. Quantitative BKV DNA PCR and urinary cytology surveillance were performed regularly after transplantation in 229 kidney recipients. Patients with BK viremia and BKVAN were treated with 30-50% reduction in doses of tacrolimus and/or mycophenolate mofetil and were monitored for BKV every 3-6 months. All the patients were followed for 5 years. Overall 5-year patient and graft survival were 95.6% and 92.1%, respectively, and independent of presence of decoy cells, BK viruria, viremia, or BKVAN. After reduction of immunosuppression, BK viremia (n = 38) resolved in 100% of patients, without increased acute rejection. Recurrent BK viremia was not observed in viremic patients without BKVAN (n = 30). All BKVAN patients (n = 7, 3.1%) cleared viremia with a mean time of 5.9 months (range 1-15 months) and manifested no decline in estimated glomerular filtration rate from 1 month to 5 years after transplantation. Viral monitoring and preemptive reduction of immunosuppression resulted in the successful resolution of BK viremia and BKVAN with excellent graft survival and renal function at 5 years.

Efficacy and safety of thymoglobulin and basiliximab in kidney transplant patients at high risk for acute rejection and delayed graft function.

OBJECTIVES To compare the efficacy and safety of thymoglobulin compared with basiliximab in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function. MATERIALS AND METHODS A retrospective review of patients who had 1 or more risk factors for acute rejection and delayed graft function and who were given either thymoglobulin or basiliximab for induction therapy. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, chronic rejection, cancer, infection, leucopenia, and thrombocytopenia were compared between thymoglobulin and basiliximab groups. Serum creatinine levels within 1 year and long-term graft and patient survival also were compared. RESULTS A total of 327 patients were included. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, and chronic rejection were significantly lower in the thymoglobulin group than in the basiliximab group (P < .05). Serum creatinine levels were lower in the thymoglobulin group on postoperative days 7, 14, and 30 (P < .05). There were no statistically significant differences regarding long-term graft and patient survival, cancer, or total infection rate between the groups. Incidences of Cytomegalovirus infection, leucopenia, and thrombocytopenia were significantly higher in the thymoglobulin group (P < .05). CONCLUSIONS Thymoglobulin may improve short-term outcomes, compared with basiliximab, in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function. However, long-term outcomes are similar with thymoglobulin and basiliximab.

Noninvasive tool for the diagnosis of polyomavirus BK-associated nephropathy in renal transplant recipients.

Noninvasive methods can facilitate early diagnosis of BK virus (BKV) replication and guide the evaluation of BKV-associated nephropathy (BKVAN). We developed 3 noninvasive methods for BKVAN screening including quantitative polymerase chain reaction (PCR) assay for BKV DNA load in urine and plasma, and quantitative assay of urine cytology by light microscopy or electron microscopy, and used these assays concurrently with renal transplant biopsies for the evaluation of 338 patients. BKVAN was diagnosed in 24 (7.1%) of 338 renal recipients. The median level of the 3 methods was the highest in pattern B of BKVAN (P < 0.05). Using these 3 methods for pattern B of BKVAN yielded a high sensitivity of 100%. Using decoy cells without quantitation had a sensitivity of 95.8% and a specificity of 83.1% for BKVAN. The amount of decoy cells in urine samples was related to BKV DNAuria, BKV DNAemia, and the pattern of BKVAN. Using a decoy cell threshold of >5 per 10 high-power fields (HPF) had an ideal sensitivity and specificity for high-risk BKVAN and BKVAN. Using a decoy cell threshold of >20 per 10 HPF for BKVAN had a specificity of 99.7%. Quantitative assay of urine cytology is a very convenient and sensitive method for diagnosis of BKVAN, which can be deemed as an additional diagnostic method for quantitative PCR screening with increased accuracy.

Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus –Associated Nephropathy after Renal Transplantation

Background Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. Methods Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. Results After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. Conclusions The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.

Kidney transplantation from living related donors aged more than 60 years: a single center experience

Abstract Objectives: To evaluate whether the outcomes of renal grafts from living related donors more than 60 years old are acceptable, in terms of renal function and patient/graft survival. Material and Methods: Twenty-one patients who received kidneys from donors older than 60 years constituted the study group (Group 1). The control group (Group 2) consisted of 110 patients who received renal transplants from ideal donors, aged 18 to 45 years. The recipients were analyzed for posttransplantation serum creatinine, the number of acute rejection episodes and delayed graft function, and patient/graft survival. Results: The mean age of donors was 62.6 ± 2.2 years in Group 1 and 32.8 ± 7.0 years in Group 2. Recipient serum creatinine was higher on postoperative day 1, year 1, year 5 in Group 1 than that in Group 2 (536.8 ± 203.3 vs. 409.8 ± 213.8, 142.4 ± 38.2 vs. 100.3 ± 22.9, 152.6 ± 42.7 vs. 107.1 ± 22.1, respectively; all p < 0.05). Acute rejection was seen in 4 cases in Group 1 (19.0%) and in 15 cases in Group 2 (13.6%; p = 0.759). Delayed graft function was seen in two cases in Group 1 (9.5%) and in four cases in Group 2 (3.6%; p = 0.540). One-, 3- and 5-year patient survival was 100%, 100% and 100% for Group 1, and 97%, 97% and 97% for Group 2. Corresponding death-censored graft survival was 100%, 100% and 100% for Group 1, and 98%, 98% and 96% for Group 2. No significant difference was observed in terms of patient/graft survival. Conclusions: Although compromising renal function, donor age did not affect patient and graft survival in the 5-year follow-up in our study. Age alone seems not to be an exclusion criterion to living kidney donation.

Calcineurin Inhibitor Conversion to Rapamycin Can Improve Graft Function in Living Donor Kidney Transplantation With Older Donors

BACKGROUND Recipients of living donor kidney transplantations from older donors often experience a lower glomerular filtration rate (GFR) than those from young donors. Calcineurin inhibitors (CNI) may cause nephrotoxicity, especially in recipients of older donor organs. The aim of this study was to investigate whether CNI withdrawal and conversion to rapamycin improved graft function among transplantation recipients of living donor kidneys from older donors. METHODS We collected 83 living donor kidney transplantations using donors aged >50 years from January 2004 to December 2009, including 25 who underwent conversion to rapamycin at the end of 3 months, while 58 cases were maintained on CNI. Baseline characteristics, complications, and graft functions were compared between the groups. RESULTS Donor age, recipient age, body weight, human leukocyte antigen mismatch, delayed graft function, acute rejection rate, serum creatinine, and estimated GFR were comparable between the 2 groups at the end of 3 months. The 1-year serum creatinine were 111.8 ± 25.5 μmol/L in CNI withdrawal versus 132.5 ± 35.9 μmol/L in the CNI-maintained group (P = .013) with 1-year estimated GFR of 86.9 ± 8.2 mL/min versus 77.4 ± 7.2 mL/min and 3-year estimated GFR of 76.1 ± 7.8 mL/min versus 67.0 ± 6.4 mL/min, respectively (both P < .001). The rates of acute rejection were 24% versus 22.4%, and chronic rejection, 4.0% versus 10.3% respectively (P > .05). One CNI withdrawal patient (4.0%) lost the graft function while 4 (6.9%) did so in the CNI-maintained group (P > .05). Logistic multivariate regression showed that maintained CNI usage, acute rejection episodes, and female donors to male recipients were independent risk factors for abnormal 1-year serum creatinine levels (P < .05). CONCLUSION CNI withdrawal with conversion to rapamycin improved graft function in living donor kidney transplantations from older donors.

Kidney Transplantation From Donors After Brain or Cardiac Death in China—A Clinical Analysis of 94 Cases

BACKGROUND We analyzed outcomes of kidney transplantation (KTx) from donation after brain death (DBD) or cardiac death (DCD) in China under the current level of the health care system. METHODS Among 94 KTx performed from February 2007 to March 2012 in two organ transplant centers in the south of China, 50 KTx were used DBD and 44 DCD donors. We retrospectively analyzed the clinical outcomes. RESULTS At a mean follow-up of 25.5 months, the 1-year and 2-year graft survival rates were 96.8% and 95.2% respectively. Delayed graft function (DGF) occurred in 27.7% recipients, three of whom lost graft function. Among six observed acute rejection episodes, five were reversed. When compared to the DCD group in DBD patients were apt to recover from DGF. Serum creatinine decreased more promptly in the DBD than in DCD group. Serum creatinine in the DCD group increased after months 12, when it was significantly higher than that in the DBD group (P < .05). CONCLUSIONS Kidney transplantation from DBD donors showed good outcomes with few complications. Although KTx from DCD donors showed a higher DGF rate and longer duration of graft recovery, we achieved favorable short-term clinical outcome using this source.

Kidney Transplantation From Donation After Cardiac Death Donors in China—A Single-Center Experience

OBJECTIVE To report clinical outcomes of kidney transplantation from cardiac death donors (DCD) in China, and to investigate its feasibility to expand the organ donor pool. PATIENTS AND METHODS We retrospectively studied clinical data of 46 DCD kidneys from 31 donors from February 2007 to August 2011. Recipients were followed for patient and graft survival. RESULTS We discarded the organs from 3 of 29 (10.3%) DCD donors and 7 of 42 (16.7%) kidneys that displayed renal thrombosis. Of the 39 recipients engrafted with DCD kidneys successfully, the mean follow-up was 16 months, (range = 50 days to 43 months). Delayed graft function (DGF) occurred in 15 (38.5%) recipients, who except one recovered within 3 months. Three biopsy-proven acute rejection episodes were observed in two recipients (5.1%). All patients survived through the follow-up. The graft survival rate was 97.4% at 12 months and 94.9% at 24 months. A 45-year-old male recipient who received a pair of grafts from a 6-year-old child survived with good renal function. CONCLUSION Although kidney transplantations from DCD donors showed a higher rate of DGF with a longer duration of graft recovery, we achieved favorable short-term clinical outcome in terms of graft survival and function. Donation after cardiac death can expand the organ donor pool in China.