Research highlights on kidney transplantation in 2022 from China / 器官移植

As a mature organ transplantation surgery, kidney transplantation has become the best means for treating end-stage renal diseases and improves the quality of survival of patients. However, there are still many challenges after kidney transplantation, such as rejection, infection, ischemia-reperfusion injury and fibrosis of transplant kidney, which seriously affect the efficacy of kidney transplantation. With the development of translational medicine, regenerative medicine, biomaterials and other emerging fields, Chinese research teams continue to work hard and publish many bright researches to solve various clinical problems related to kidney transplantation. This article reviews the basic and clinical frontiers of kidney transplantation in 2022 as well as the new techniques and advances in the field of transplantation, focuses on the achievements made by the Chinese team in the field of transplantation in 2022, and provides ideas for solving the major clinical problems of kidney transplantation from the perspective of localization to promote the further development of kidney transplantation in China.

Effects of Tacrolimus Combined with Valsartan in Immunosupperessive regimen on Renal Function and Lipid Metabolism in Patients with Chronic Allograft Dysfunction and Its Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of tacrolimus combined with valsartan in immunosuppressive regimen on renal function， lipid metabolism and matrix metalloproteinase 2 （MMP-2）， MMP-9， tissue inhibitors of matrix metalloproteinases 2 （TIMP-2） and transforming growth factor-β （TGF-β） in patients with chronic allograft dysfunction （CAD）. METHODS： CAD patients admitted to nephrology department of our hospital from Mar. 2016 to Jun. 2018 were enrolled in group A， B， and C according to the random number table， 34 cases in each group. Group A was given cyclosporin A+Mycophenolate capsules+Prednisone acetate tablets； group B was treated with tacrolimus+Mycophenolate capsules+Prednisone acetate tablets； group C was treated with valsartan on the basis of group B； they were treated for continuous 3 months. Renal function indexes （24 h urinary protein， Scr）， lipid metabolism indicators （TC， TG， HDL， LDL） and the levels of MMP-2， MMP-9， TIMP-2 and TGF-β were compared among those groups. RESULTS： Before treatment， there was no statistical significance in above indexes among 3 groups （P＞0.05）. After treatment， 24 h urinary protein， Scr and TC levels of group A were still higher than normal level， while other lipid metabolism indexes were within normal range. 24 h urinary protein and TC level of group B were still higher than normal level， while Scr level was near the upper limit of the normal range， and other lipid metabolism indicators were within the normal range. Renal function indexes and lipid metabolism indexes of group C were within normal range， while renal function indexes levels of it were lower than those of group B （P＜0.05）； there was no statistical significance in lipid metabolism indexes， compared with group B （P＞0.05）. Compared with before treatment， TGF-β level of group A was significantly increased （P＜0.05）； there was no statistical significance in MMP-2， MMP-9 or TIMP-2 levels （P＞0.05）. TGF-β level of group B and group C was increased significantly （P＜0.05）， while the levels of MMP-2， MMP-9 and TIMP-2 were decreased significantly （P＜0.05）. CONCLUSIONS： Tacrolimus combined with valsartan can effectively delay renal dysfunction and improve lipid metabolism in CAD patients. The mechanism may be related to the inhibition of TIMP-2， MMP-2， MMP-9 and TGF-β expression.

Clinical significance of Th17 cells in kidney transplantation

Transplantation research has focused on cytotoxic T-cell and plasma cell/B-cell-targeted strategies, but little attention has been paid to the role of T helper 17 (Th17) cells in allograft dysfunction. However, accumulating evidence suggests that Th17 cells contribute to the development of acute and chronic allograft injury after transplantation of various organs, including the kidney. This review summarizes recent reports on the role of Th17 cells in kidney transplantation. Means of improving allograft outcomes by targeting the Th17 pathway are also suggested.

Biomarkers for long-term survival of renal graft: Recent progress / 第二军医大学学报

How to maintain a good long-term graft function is currently the most prominent problem in renal transplantation. Due to inefficiency of the existing diagnostic tools, extensive studies have been made to search for novel biomarkers and have made rapid progression. Here we aimed to make a brief review of important biomarkers that have been shown relevant to the long-term outcome of renal graft.

A Case of Transplant Glomerulopathy Complicated by Crescent Formation / 대한이식학회지

Transplant glomerulopathy (TGP) is specified as thickening of capillary wall of glomerulus and clinically presented with proteinuria and progressive graft dysfunction. In contrast, crescent formation represents an extracapillary proliferative glomerular change and is clinically presented with rapidly progressive renal failure. Previously, in transplant kidneys, crescent formation was reported only in anti-GBM disease and ANCA- associated vasculitis. Here we report a case with a very unusual combination of transplant glomerulopathy and crescent formation. Ten years after the renal transplantation the patient was admitted due to proteinuria and progressive azotemia. Although his underlying renal disease was IgA nephropathy, the transplant kidney biopsy revealed typical findings of transplant glomerulopathy without specific immune deposits, but with extensive cellular crescents. Methylprednisolone pulse therapy was not successful, and he was switched to maintenance hemodialysis.

Post-Renal Transplantation Dyslipidemia / 대한이식학회지

Long-term survivors in renal transplantation have been increasing, as medical care has improved in addition to development of new immunosuppressants. Therefore, cardiovascular disease, especially ischemic heart disease and chronic allograft dysfunction have become main obstacles to longer survival and better quality of life. Dyslipidemia, which is a well-known risk factor of ischemic heart disease in general population, is more common in renal transplantation patients. Moreover, dyslipidemia is suggested as a nonimmunological risk factor of chronic allograft dysfunction. Therefore, it is important to manage dyslipidemia properly to improve patient and graft survival in renal transplantation. But, specific approach, tailored to renal transplant patients is necessary in the treatment of dyslipidemia, because there are significant differences between renal transplantation patients and general population. We present here, epidemiology, mechanism, and impact of dyslipidemia on ischemic heart disease and chronic allograft dysfunction, and overall approach to dyslipidemia in renal transplantation patients, including treatment guideline.

Peritubular Capillary C4d Deposition in Chronic Allograft Dysfunction

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.

Association of Polymorphisms of the TNF-alpha and TGF-beta1 Genes with Renal Allograft Dysfunction / 대한이식학회지

PURPOSE: Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 have been shown to play important roles in allograft rejection of various organs. This study was performed to evaluate the association of TNF-alpha and TGF-beta1 genes and renal allograft dysfunction. METHODS: Five TNF-alpha ( 1,031 T/C, 863 C/A, 857 C/T, 308 G/A, 238 G/A) and two TGF-beta1 (codon 10 T/C, codon 25 G/C) single nucleotide polymorphism (SNP) sites were studied using PCR-SSCP and PCR-RFLP methods in 100 controls and 165 patients underwent renal transplantation. For the TGF-beta1 gene, we also studied the polymorphism of donors. RESULTS: The allele frequencies of each SNP sites in controls were not different from those of patients. The phenotype frequency of TNF-alpha high producer type, 308 A was significantly higher in the patients with recurrent acute rejection episodes (REs) compared with patients with no or one RE (38.5% vs. 9.2%, P=0.007). The frequency of TGF-beta1 low producer genotype, codon 10 CC was also significantly higher in the patients with recurrent REs (53.8% vs. 22.4%, P=0.029). Analysis of chronic renal allograft dysfunction (CRAD) revealed that the TGF-beta1 high producer type, codon 10 T allele in donors was associated with CRAD (66.7% vs. 48.2%, P=0.043). This association was significant only among patients with recurrent REs. Occurrence of CRAD was not influenced by TGF-beta1 polymorphisms in the patients. CONCLUSION: These results would be useful for predicting high risk group for acute rejection or CRAD in renal transplantation and might be useful for implying individualized immunosuppressive therapy.

Tacrolimus plus Mycophenolate Mofetil(MMF) for Patients with Chronic Allograft Dysfunction / 中国药房

OBJECTIVE:To discuss our experience of switching use of immunosuppressive agents for patients after renal transplantation.METHODS:23 patients with chronic allograft dysfunction(CAD) were treated with tacrolimus + mycophenolate mofetil instead of cyclosporine A+ azathioprine.The change of renal function and the adverse effects were observed.RESULTS:The serum creatinine(Scr) level before and after therapy conversion were 167～478 ?mol?mL-1 with a mean value of(268?78) ?mol?mL-1 and 112～346 ?mol?mL-1 with a mean value of(174?65) ?mol?mL-1,respectively,showing significant difference in the t test(P

Study on the Factors Affecting the Chronic Renal Allograft Dysfunction / 대한신장학회잡지

We studied the chronic renal allograft dysfunction in Korean renal transplants from 1 year after transplantation to 5 years. We evaluated renal function by simply using the reciprocal serum creatinine level and sought to find factors affecting the value of the reciprocal serum creatinine and graft survival, and changes of the slope of reciprocal serum creatinine. We also estimated the reciprocal serum creatinine from demographic parameters and routine laboratory results. This study included 114 patients, 87 male and 27 female who underwent renal transplantations and had functioning allografts for more than 18 month after transplantation. The results were as follows. 1) The reciprocal serum creatinine level decreased slowly and linearly. 2) There were many factors related to the reciprocal creatinine, including blood urea nitrogen, serum uric acid level, age of donors, sex of recipients, presence of acute rejecton, age of recipient, serum phosphorus, white cell count in blood, cyclosporine level in blood, hemoglobin level, posttransplantation period. We could derive the estimated reciprocal serum creatinine from data of the patients. 3) The age of the recipient and cyclosporine level at 1 year after transplantation affected the slope of the reciprocal serum creatinine during follow-up time. 4) There were 16 graft loss, including 3 functioning graft loss and 13 graft loss due to chronic allograft dysfunction. 5) Besides creatinine and BUN level at 1 year, higher blood pressure and proteinuria and lower hemoglobin levels at 1 year after transplantation were related to the graft loss from chronic allograft dysfunction. 6) There were more chronic allograft loss in patients who had lower actuarial reciprocal serum creatinine than estimated reciprocal serum creatinine. Because follow-up time was relatively short and there were only mild increases in serum creatinine level in our study, follow up of our patients for a longer-term period is required to find other factors affecting the renal allograft dysfunction.

Treatment of chronic allograft dysfunction with mycophenolate mofetil after kidney transplantation:a multicenter study / 中华器官移植杂志

Objective To investigate the therapeutic effectiveness and safety of mycophenolate mofetil (MMF) in the treatment of chronic allograft dysfunction (CAD).Methods Seventy-eight patients with CAD were administrated with MMF substituting for Aza or CTX with concomitant low-dose CsA. The effectiveness and complications were analyzed. The mean follow-up time after MMF treatment was 9.48 months.Results After treatment with MMF in combination with low doses of CsA and Pred,the serum creatinine concentration (SCr) in 74 CAD patients was significantly decreased and remained stable at the end of follow-up ( P