Shuming Ji

De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection

Anti-endothelial cell antibodies (AECAs) are thought to be involved in the development of renal allograft rejection. To explore this further, we determine whether AECAs play a role both in predicting the incidence of allograft rejection and long-term outcomes by analysis of serum samples from 226 renal allograft recipients for AECAs pre- and post-transplant. Surprisingly, the presence of pre-existing AECAs was not associated with either an increased risk of rejection or a detrimental impact on recipient/graft survival. Subsequent de novo AECAs, however, were associated with a significantly increased risk of early acute rejection. Moreover, these rejections tended to be more severe with a significantly increased incidence of both steroid-resistant and multiple episodes of acute rejection. The acute rejections associated with de novo AECAs did not correlate with C4d deposition at the time of renal biopsy, but did demonstrate an association with the presence of glomerulitis and peritubular capillary inflammation. Significantly more patients with de novo AECAs developed graft dysfunction. Thus, our prospective study suggests the emergence of de novo AECAs is associated with transplant rejection that may lead to allograft dysfunction.

Effect of CYP3A5 Genotype on Renal Allograft Recipients Treated With Tacrolimus

OBJECTIVE Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months. METHODS Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy. RESULTS There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group. CONCLUSION CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.

The fate of glomerular mesangial IgA deposition in the donated kidney after allograft transplantation

Objective:  To investigate the fate of the mesangial IgA deposits in the donor kidney after allograft transplantation.

Recurrent or De Novo IgA Nephropathy with Crescent Formation after Renal Transplantation

IgA nephropathy is the most common glomerular disease in China, accounting for 38.8% of primary glomerular disease. It has been reported that 20.8% patients of IgA nephropathy had a different degree of crescent formation. From January 1995 to December 2004, 1000 patients had undergone cadaveric renal transplantation, and 1742 allograft renal biopsies were reviewed in the Department of Nephrology at Jinling Hospital, Nanjing University. Among them, 18 cases were found with crescent formation, in which 10 patients were diagnosed as recurrent or de novo IgA nephropathy because their immunofluorescence showed strong IgA deposition in mesangial area and capillary. The initial treatment protocol was CsA+Azp+Pred, except in two cases of CsA+MMF+Pred. There were 8 males and 2 females, with ages from 25 to 69 (mean of 37.1) years old. All of them showed progressive renal dysfunction with increasing level of serum creatinine ranged from 1.48 to 6.25 mg/dL. Seven cases presented edema with an increasing level of proteinuria (1.36 to 3.58 g/24hr), and nine cases presented with hematuria ranging from 50 to 1250 × 104/mL (one showed gross hematuria). In pathological examinations, they showed mesangial proliferation and matrix expansion with 10% to 66.7% crescents (mean of 37.5%) in their allograft renal biopsys samples. All patients changed their immunosuppressive regimens; however, nine of them eventually advanced to ESRD and returned to hemodialysis after 6 to 36 months. Two cases received second renal transplantation after six months to five years, and one kept stable renal function with 2.5 mg/dL of serum creatinine after three years of follow-up. IgA nephropathy with crescentic formation was not rare in renal allografts or native glomerulonephritis in Chinese patients. These patients showed rapidly progressive renal dysfunction, and most of them lost graft function and needed hemodialysis therapy.

An aggressive systematic strategy for acute respiratory distress syndrome caused by severe pneumonia after renal transplantation

Acute respiratory distress syndrome (ARDS) caused by pneumonia after renal transplantation was usually associated with overimmunosuppression and high mortality rate. We evaluated the efficacy of an aggressive systemic protocol including strategies improving bodys immune function. Twenty‐one recipients were enrolled in this study. Patients were subjected to a protocol including (i) withdrawal of most immunosuppressants, (ii) early use of immunoenhancers and continuous renal replacement therapy (CRRT), (iii) reasonable administration of antibiotic regimen, (iv) prompt mechanical ventilating strategy, and (v) adequate nutrition. Immunosuppressants were adjusted according to the value of CD4+, CD8+T lymphocytes in peripheral blood. CRRT was conducted at once when patients were admitted to the intensive care unit (ICU), regardless the graft function. Thirteen (62%) survived and eight died finally. This is a high survival rate for this kind of patients. Eighteen patients had received thymosin treatment. All patients who survived experienced renal allograft dysfunction during CRRT, but when CRRT stopped, the function of all grafts gradually recovered. No acute rejection episodes were documented during the treatment. The aggressive systemic protocol including strategies improving the bodys immune function and CRRT can improve the outcome of patients with ARDS after renal transplantation. The count of CD4+, CD8+T lymphocytes of peripheral blood is useful in the adjustment of immunosuppressants and the prediction of patient outcome.

Pulmonary Lophomonas blattarum infection in patients with kidney allograft transplantation

The aim of the study was to analyse the clinical manifestation and management of pulmonary Lophomonas blattarum infection in four allograft transplantation recipients retrospectively. Four patients with pulmonary L. blattarum infection were diagnosed by using Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) examination. Their clinical manifestation and management are summarized. Four cases of pulmonary L. blattarum were found during the period from the second month to the third month after transplantation. Concurring infection by other pathogens was found in three of them. Common initial symptoms included fever (>38 °C) without cough and breathlessness. Lower lobe shadowing could be found on chest X‐ray. Body temperature decreased to the normal range in three patients and to 37.5 °C in the other one, after intravenous injection of metronidazole and tapering immunosuppressant. Radiological examination confirmed improved health condition of the patients afterwards. Two patients received repeated FOB and only dead L. blattarum was found. Pulmonary L. blattarum infection in allograft transplant recipients carry relatively obscure initial symptoms. Possible L. blattarum infection needs to be screened in post‐transplantation pulmonary infection patients with similar symptoms, especially in those who respond poorly to anti‐infection treatment. Microscopic examination of BAL fluid can help to identify pulmonary L. blattarum infection and metronidazole is an ideal treatment choice.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

Evaluation of vascular lesions using circulating endothelial cells in renal transplant patients.

To investigate the correlation between circulating endothelial cells (CECs) and vascular lesions in renal allografts.

The Prevalence of Immunologic Injury in Renal Allograft Recipients with De Novo Proteinuria

Post-transplant proteinuria is a common complication after renal transplantation; it is associated with reduced graft and recipient survival. However, the prevalence of histological causes has been reported with considerable variation. A clinico-pathological re-evaluation of post-transplant proteinuria is necessary, especially after dismissal of the term “chronic allograft nephropathy,” which had been considered to be an important cause of proteinuria. Moreover, urinary protein can promote interstitial inflammation in native kidney, whether this occurs in renal allograft remains unknown. Factors that affect the graft outcome in patients with proteinuria also remain unclear. Here we collected 98 cases of renal allograft recipients who developed proteinuria after transplant, histological features were characterized using Banff scoring system. Cox proportional hazard regression models were used for graft survival predictors. We found that transplant glomerulopathy was the leading (40.8%) cause of post-transplant proteinuria. Immunological causes, including transplant glomerulopathy, acute rejection, and chronic rejection accounted for the majority of all pathological causes of proteinuria. Nevertheless, almost all patients that developed proteinuria had immunological lesions in the graft, especially for interstitial inflammation. Intraglomerular C3 deposition was unexpectedly correlated with the severity of proteinuria. Moreover, the severity of interstitial inflammation was an independent risk factor for graft loss, while high level of hemoglobin was a protective factor for graft survival. This study revealed a predominance of immunological parameters in renal allografts with post-transplant proteinuria. These parameters not only correlate with the severity of proteinuria, but also with the outcome of the graft.

Observation of Efficacy and Safety of Converting the Calcineurin Inhibitor to Sirolimus in Renal Transplant Recipients With Chronic Allograft Nephropathy

OBJECTIVE The objective of this study was to evaluate the efficacy and safety of converting from a calcineurin inhibitor (CNI) to sirolimus among renal transplant recipients with chronic allograft nephropathy (CAN). METHODS In 16 patients with CAN, substituted sirolimus for CsA or FK506 and observed the incidence of acute rejection and changes in serum creatinine, triglycerides, cholesterol, blood uric acid, and peripheral blood leukocyte/platelet counts within 12 months. All recipients underwent an allograft biopsy before conversion. The targeted sirolimus level was 4-8 ug/L. RESULTS After conversion to sirolimus, the creatinine level of 7 cases decreased and the efficacy rate was (43.8%). No acute rejection occurred during the follow-up. The cases with hypercholesteremia increased from 3 to 7 after conversion; hypertriglyceridemia increased from 3 to 5; leukopenia occurred in 2; subnormal platelet counts increased from 2 to 3; and hyperuricemia increased from 6 to 7. Meanwhile, the average level of peripheral blood leukocytes obviously decreased in the first month, the average peripheral blood cholesterol increased over 12 months, but the average content of peripheral blood platelets, triglyceride and blood uric acid failed to display as statistic difference. Eight patients showed C4d deposition in peritubular capillary in graft tissue before conversion, 7 cases of whom showed no improvement in renal function. In 6 cases there was no C4d deposition in peritubular capillary in graft tissue. Only 2 of 6 cases showed no improvement in renal function. There were 6 patients whose creatinine level was <2.48 mg/dL before conversion, and renal function in 5 of them improved in a year after conversion. In contrast, among 10 patients whose blood creatinine level was >2.48 mg/dL, only 2 cases improved. CONCLUSION It is safe for patients with CAN to use substitute sirolimus for CNI; the incidence of acute rejection did not increase. In this study, 43.8% of patients showed improved renal function. The main adverse reactions after conversion to sirolimus were hypercholesteremia and decreased peripheral blood leukocytes. The serum creatinine level and the deposition of C4d in peritubular capillary were important factors influencing therapeutic efficacy.