Objective Sirolimus ( SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after re-nal transplantation.Nevertheless, the occurrence of proteinuria has recently been recognized among patients treated with SRL-based therapy.The aim of this study was to investigate the therapeutic effect of tripterygium wilfordii hook F ( T II) on proteinuria caused by SRL in renal transplant recipients who were treated by trilogy immunosuppressive therapy of sirolimus combined with mycophenolate and hormone. Methods 52 recipients were divided into 2 groups randomly:TⅡgroup (n=27) and valsartan group (n=25).The TⅡgroup was administered 1 mg/kg/d, and the valsartan group 80-160 mg/d for consecutive 12 months.Based on primary trilogy immu-nosuppressive therapy of sirolimus combined with mycophenolate and hormone, the dosage of sirolimus was adjusted according to the target concentration 6-10 ng/ml( ELASA approach) and mycophenolate was administered 750 mg twice per day, adjusting dosage ac-cording to the mycophenolate AUC 0-12 level(35-45 mg· h/L).The evaluation of therapeutic effect includes: complete remission, proteinuria decreased by>50%; partial remission, proteinuria decreased by 20% to 50%; ineffective, proteinuria decreased by<20%. Results During the 12 month follow-up, the total effective rates in the TⅡgroup and the valsartan group were 95.2%and 86.7%respectively, in which the TⅡ group decreased more significantly (P<0.01).The total cholesterol level and triglyceride level in TⅡgroup were obviously lower than those in valsartan group(P<0.01). The total cholesterol level and triglyceride level in valsartan group increased ([6.60±0.2]mmol/L vs [7.11±1.13]mmol/L, [2.47± 1.48]mmol/L vs [2.49±0.32] mmol/L).The serum protein level in TⅡ group was obviously higher than that in valsartan group ([41.1±1.2]g/L vs [37.9±4.2]g/L, P<0.05).At 3 month, 6 month and 12 month follow-up, the average serum creatinine levels in TⅡgroup were obviously lower than those in valsartan group ([1.5±0.4]mg/dl vs [1.6±0.3]mg/dl, P<0.05), ([1.3±0.3]mg/dl vs [1.8±0.5]mg/dl, P<0.05), ([1.1±0.4]mg/dl vs [2.1±0.5]mg/dl, P<0.05).The incidence rate of adverse reaction in valsartan group was obviously greater compared with TⅡgroup( P<0.05) . Conclusion Both tripterygium wilfordii multiglycosides and valsar-tan can reduce proteinuria caused by SRL in renal transplant patients,while the application of TⅡhas more remarkable effect.

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.

Objective Little research has been done on the risk factor analysis of BK virus(BKV) infection in renal transplant recipients in Chinese population.The article aimed to investigate BKV infection and analyze its risk factors in renal transplant recipients in China.Methods Renal transplant recipients who had received the detection of BKV DNA in urine and blood samples in Nanjing General Hospital from June 2015 to July 2016 were selected, while the patients with uremia hemodialysis and healthy living donors were included as control group.According to the detection results of BKV DNA in urine and blood samples, renal transplant recipients were divided into BKV DNA positive group(n=89, positive urine or blood and urine BKV DNA) and BKV DNA negative group(n=359, negative blood and urine BKV DNA).Analysis was made on BKV infection in renal transplant recipients in order to investigate the effects of factors including clinical condition, postoperative complications and immunosuppressive regimen on BKV infection.Results The positive rate of BKV DNA in urine samples of renal transplant recipients was 19.9%, which was higher than those of patients with dialysis and healthy living donors(6.3% and 4.2% respectively, P<0.001).Multivariate logistic regression analysis showed BKV infection was associated with pulmonary infection(OR[95%CI], 3.468[1.227-9.802];P=0.019) , acute rejection (OR[95%CI], 2.645[1.142-6.127];P=0.023), and FK506 (OR[95%CI], 2.408[1.104-5.254];P=0.027).Conclusion The incidence of BKV infection in renal transplant recipients increases significantly.Pulmonary infection, acute rejection and FK506-based immunosuppressive regimen are risk factors leading to BKV infection.

Objective To investigate the renal pathologic changes in both donors and transplant recipients with delayed graft function (DGF).Methods The clinical and laboratory data were retrospectively analyzed in 144 renal recipients with DGF.All the patients received renal biopsy,and donors' biopsy was performed on 131 recipients.The pathological changes were examined under the light microscopy (LM),immunofluorescence (IF) and electron microscopy (EM).Results (1) The incidence of DGF was 10.16%-7.48% during 1994 to 2005,and decreased to 5.35 % during 2006 to 2009.(2) Anuria occurred in 24 cases (16.67 %),oliguria in 24 (16.67%) and hypertension in 68 cases (47.22 %).The enlargement of transplanting kidney and the increased vascular resistance was detected in 79.67 % (98/123 cases) and 45.53 % (56/123 cases) respectively by ultrasound examination.(3) The level of serum creatinine was ranged from 451 to 707 μmol/L.The high level of urinary NAG enzyme was found in 102 cases (70.83 %),proteinuria in 79 recipients (54.86 %) and hematuria in 77 cases (53.47 %).(4) The acute rejection was observed in 66 cases (45.83 %),toxicity of CNI in 22 (15.28 %),IgA nephropathy in 18 (12.50 %),acute tubular necrosis in 8 (5.56 %),and recurrent FSGS in 2 cases (1.39 %).(5) In most recipients (66/109 cases,60.55 %)immunosuppressive regimen altered and renal replacement therapy was given.Conclusion The causes of DGF are complicated.The quality of donors' kidney and early histological changes of recipients are contributed to the development of DGF.It is necessary to perform renal biopsy not only in donors but also in recipients with DGF.And kidney biopsy in transplanted patients was also beneficial to the treatment.

Objective To discuss the clinicopathological characteristics and prognosis of the recurrence of IgA nephropathy (IgAN)after renal transplantation.Methods A total of 1 48 patients,pathologically diagnosed with IgAN which progressed into end-stage renal failure,undergoing renal transplantation in National Clinical Medical Research Center of Kidney Diseases,Nanjing General Hospital of Nanjing Military Command from January 1 996 to April 2009,were included in this study.According to whether IgAN recurred,all patients were assigned into recurrence (n =46)and non-recurrence groups (n =1 02).Urinary red blood cell (U-RBC)count,24 h urinary protein level,renal function including serum creatinine (Scr)and glomerular filtration rate (GFR)at 0,1 ,2,3 and 5 years after renal transplantation were statistically compared between two groups.The incidence of histopathological renal injury and survival rate of transplant kidneys was compared between two groups.Results In recurrence group,U-RBC count and 24 h urinary protein level were gradually elevated and renal function steadily declined.Compared with non-recurrence group,U-RBC count at 2-,3-and 5-year after renal transplantation significantly increased,and renal function was significantly aggravated at postoperative 5 years (all in P<0.01 -0.001 )in recurrence group.Renal pathological findings revealed that compared with non-recurrence group,the incidence of cellular crescent formation,glomerulus adhesion,mesangial cell proliferation,increased mesentery matrix, glomerulosclerosis,segmental glomerulosclerosis,glomerular dysfunction and tubulointerstitial fibrosis was significantly higher in recurrence group (all in P <0.001 ).After renal transplantation,chronic kidney injury index in recurrence group was 7.7 ±2.3,which was significantly higher than 4.6 ±1 .4 in non-recurrence group (P <0.01 ).Compared with non-recurrence group,the incidence of chronic rejection,glomerulopathy of transplant kidney (without IgAN)and positive C4d deposition was significantly higher in recurrence group (P <0.01 -0.001 ).At 1 -and 3-year after renal transplantation, survival rates of transplant kidney did not significantly differ between recurrence and non-recurrence groups (93.8% vs.86.7%,95.6% vs.88.3%,both in P >0.05).However,the survival rate at 5 years after transplantation was 51 .4% in recurrence group,significantly lower compared with 83.8% in non-recurrence group (P <0.001 ).In recurrence group,1 0 patients (22%)presented with renal failure after renal transplantation,and 9 patients (9%)in non-recurrence group.Conclusions After renal transplantation,the recurrence of IgAN characterized by asymptomatic microscopic hematuria, albuminuria and progressive aggravation of renal function reduce long-term survival rate of renal graft and indicate poor prognosis.

Objective: To evaluate the efficacy and safety of bortezomib in kidney transplant recipients with chronic active antibody-mediated rejection (cABMR). Methods: A retrospective study wad conducted in patients(n=136)fulfilling the Banff 2017 criteria for cABMR from January 2004 to July 2017, including 29 patients bortezomib group and 97 patients in control group. Identified cABMR patients were dichotomized into bortezomib and control groups with a 1∶1 match using the propensity score matching method. The primary outcome was initiation of replacement therapy or an estimated glomerular filtration rate(eGFR)declined to <15 ml·min^-1·(1.73m²)^-1. The prognosis and adverse reactions of two groups were analyzed and evaluated. Results: No significant inter-group differences existed in age, sex ratio, immunosuppressive regimen, allograft age, serum creatinine, eGFR, urine protein, serum albumin, hemoglobin or HCV positive rate(all P>0.05). There were no significant inter-group differences in Banff scores (g, i, t, v, ah, mm, ci, ct, cv, ptc, c4d, all P>0.05). The median survival for bortezomib group and control group was 40.7 months and 36.9 months respectively. No statistically significant difference in graft survival between the two groups was observed(P=0.83), even after propensity score adjustment(P=0.29). The incidence of nausea, diarrhea and thrombocytopenia in bortezomib group was higher than those in control group (P<0.05). Conclusions Bortezomib does not seem to improve the prognosis of cABMR while is associated with higher incidence of adverse reactions.

Objective:To explore the clinicopathologic features and renal prognosis of patients with post-transplant membranous nephropathy (MN).Methods:Patients with allograft biopsy-proven MN were reviewed retrospectively and divided into unknown etiology group (A, n=12) and recurrent membranous nephropathy (rMN) group (B, n=7). Their clinicopathological data and renal prognosis were assessed and compared.Results:No differences existed in the proportion of living-related donor or post-transplant allograft function. Group B had recurrence at 16.4 months after transplantation and it was significantly shorter than group A. Allograft impairment manifested as proteinuria, nephrotic syndrome and/or renal insufficiency in both groups. The positive rate of serum anti-PLA2R antibody and renal PLA2R staining was significantly higher in group B than that in group A. Similarly, the intensity of IgG4 subtype staining was also stronger in group B than that in group A. The 5-year cumulative renal survival rates from end-stage renal disease (ESRD) were 77.8% and 66.7% in groups A and B respectively. No significant inter-group difference existed in renal prognosis.Conclusions:Anti-PLA2R antibody plays an important role in the recurrence of rMN after renal allografting. PLA2R staining is useful for detecting primary disease and its sensitivity is higher than that of serum anti-PLA2R antibody. Rituximab is an effective treatment for post-transplant MN. Follow-up studies with a larger sample size are required for further verification.

Objective To characterize the clinicopathologic features,treatment efficacy and prognoses of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts.Methods Electronic medical records of Jinling Hospital were searched for PGNMID that was diagnosed during January 2008 to April 2017.Clinicopathologic features,treatment regimens and prognoses information were retrieved and analyzed.Results We identified 5 cases of PGNMID with clinical symptoms of proteinuria (5/5),serum creatinine elevation (4/5) or hematuria (4/5) 5 to 19 months after kidney transplantation.Various light microscopic features were observed,with predominantly membranoprolifeative pattern.Mild mesangial proliferation pattern could be observed in early stages of disease progression.Immunofluorescence revealed monoclonal IgG3κ in 3 patients and IgG3λ in another 2 cases.One case of PGNMID with normal light microscopy but monoclonal IgG deposits was verified by IgG and light-chain subtyping.In the 4 patients treated with rituximab or bortezomib,decreased proteinuria was achieved in all treated patients while the decreases in serum creatinine decrease were only observed in 2 patients At last follow-up,one patient was in dialysis and serum creatinine levels of other 2 patients were ＞265.2 μmol/L.Conclusion Membranoprolifeative pattern is the most frequently observed microscopic findings and IgG3 is the most frequent IgG subtype in PGNMID.PGNMID recurs shortly after kidney transplantation.Rituximab and/or bortezomib is conducive to decrease proteinuria while their efficacy to decrease serum creatinine is dubious.The most effective treatment protocol for PGNMID remains to be determined in larger samples.

Objective:We aimed to evaluate the predictive value of pre-implantation biopsy combined with Lifeport for the short-term prognosis of kidney allograft from donation after citizen death (DCD).Methods:Data from a total of 34 patients who had undergone kidney transplantation in Jinling Hospital from December 2017 to December 2019 were retrospectively analyzed. Histopathological data from pre-implantation biopsy , Lifeport parameters and recipient kidney transplant function at 3 months post-surgery were collected. The performances of histopathological indexes , and Lifeport parameters to predict delayed graft function (DGF) and estimated glomerular filtration rate (eGFR) at 3 months post-surgery were observed evaluated.Results:13 cases of DGF occurred, accounting for 38.2%. Serum creatinine at death and resistance index (RI) at 0.5 h, 1 h, 2 h and 4 h after Lifeport hypothermic machine perfusion (HMP) in the DGF group was significantly higher than that in the non-DGF group. Histologically, the acute tubular injury (ATI) score of the DGF group was higher than that of the non-DGF group, whereas the Remuzzi score was not statistically different between the two groups. The eGFR at 3 months post-transplant was moderately correlated with the RI at 4 h HMP and the Remuzzi score (RI: r=-0.48, P<0.001; Remuzzi score: ρ=-0.42, P=0.01), but no correlated with ATI score of the donor kidney. Although Remuzzi score was not correlated with kidney allograft recovery time (ρ=-0.25, P=0.16), it was inversely correlated with eGFR at 3 months post-transplant (ρ=-0.42, P=0.01). Combined use of Lifeport HMP 4-hour RI and ATI score increased the sensitivity and specificity of predicting DGF to 100% (95% CI: 75.3%-100%) and 90.5% (95% CI: 69.6%-98.8%) respectively. Conclusions:The serum creatinine at death, Lifeport RI, and ATI score of the DGF group were significantly higher than those of the non-DGF group, and the eGFR at 3 months post-transplant was correlated with the Lifeport RI and Remuzzi score. Combined use of ATI score and RI at 4 hours of Lifeport perfusion improved the sensitivity and specificity of predicting DGF .

Objective:To explore the long-term prognosis of chronic active antibody-mediated rejection(cABMR)and independent risk factors for prognosis.Methods:A single-center retrospective cohort with biopsy-proven cABMR was examined. Renal biopsies were scored according to the criteria of Banff 2017. The primary outcome was death-censored graft failure defined as resuming dialysis or estimated glomerular filtration rate(eGFR)decreased to <15 ml·(min·1.73m 2) -1. The prognostic significance of clinical and histopathologic parameters were determined by a Cox proportional hazard model. Results:Clinical data from 149 cases were available for analysis with a median follow-up of 28(15~51)months. In a multivariable model, ci + ct score(HR 3.0; 95 % CI 1.9~4.7), cg score(HR 1.9; 95 %CI 1.1~3.1), eGFR(HR 2.0; 95 % CI 1.3~3.2)and proteinuria(HR 2.0; 95 %CI 1.3~3.2)were independent predictors of primary outcome.Conclusions:eGFR, proteinuria, Banff ci + ct and Banff cg are independent risk factors for the prognosis of cABMR.