Longitudinal study of the frequency of cytotoxic T cell precursors in kidney allograft recipients

Clonal deletion or inactivation of donor-specific alloreactive cells are important mechanisms that are believed to account for acquired immune tolerance in allograft recipients. Serial assessment of precursor cytotoxic T lymphocyte frequencies (CTLpf) by limiting dilution analysis (LDA) provides information at the clonal level on changes in the alloimmune response of graft recipients. We performed a longitudinal study of 15 cadaveric kidney recipients before and every 3 months throughout the first year after transplantation (Tx). Pre-Tx values of donor CTLpf showed high interindividual variability without a predictive value for the clinical outcome. All patients with well functioning kidneys had decreased CTLpf at 3 months post-Tx in comparison with pre-Tx values. This decrease was donor-specific in four patients and was permanent in two cases throughout the study. Most patients presented decreased anti-donor CTLpf values from 6 to 9 months, whereas a partial recovery of donor CTLpf was observed in three patients. Reversible acute rejection was diagnosed in three patients, and it was associated with a marked increase in anti-donor CTLpf, returning to pre-Tx values by 9 months post-Tx. In addition, one patient with chronic rejection displayed a transient increase in CTLpf 6 months after Tx. The results of this sequential study indicate the establishment of a state of either hyporesponsiveness or functional clonal inactivation, transient or permanent, which could facilitate allograft acceptance.     

测定血清及尿β2微球蛋白评估健康老年人肾功能的价值

测定72例健康老年人（60-84岁）和65例健康青中年人（20-50岁）血清和尿β2微球蛋白（β2m)，发现前血清β2m浓度比后明显增高（p<0.001)；老年组≥70岁尿液β2m浓度也明显增高（p<0.05)。结果表明肾小球滤过率下降随年龄增长而降低，以后再出现肾小管功能减退。本试验较血清尿素氮、肌酐和内生肌酐清除率测定更为敏感。     

Efficacy and safety of lowering immunosuppression to treat CMV infection in renal transplant recipients on valaciclovir prophylaxis: a pilot study.

BACKGROUND: Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis. METHODS: We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. RESULTS: The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. CONCLUSION: The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.     

咳嗽从肾论治

基于中医有关古代文献和个人的临床经验，作者举例说明咳嗽不仅能从肺治疗，从肾治疗也是行之有效的方法。     

128例肾输尿管结石临床分析

目的为探讨肾输尿管结石的临床特点,以提出更好的防治措施。方法对原西南师范大学医院1997-2004年治疗的128例肾输尿管结石病例的临床资料进行统计分析。结果本组病例男女之比为2.05∶1,29岁以下发病103例,占80.5%。2001年起发病呈上升趋势,2003年最高。每年9-10月是发病高峰,占本组病例的31.2%。经体外震波碎石99例,3个月结石排净率为83%,与文献报道的基本一致。结论该校肾输尿管结石患者,男性多于女性,30岁以下居多。发病近年增加,体外震波碎石疗效好。     

Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available. METHODS: Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50 micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC. CONCLUSIONS: In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.     

中西医结合疗法延缓慢性肾功能不全患者急性肾功能减退的临床研究

目的:探讨中医活血化瘀结合西医疗法是否具有延缓慢性肾功能不全患者急性肾功能减退的疗效.方法:回顾性分析未行透析的慢性肾功能不全患者32例,近期肾功能急性进行性减退,血尿素氮(blood urea nitrogen,BUN)、肌酐(serum creatinine,SCr)进行性升高.常规治疗基础上,均予以中药保留灌肠30 min,同时加静脉滴注活血化瘀等中西药物治疗14 d.观察治疗前后患者血常规、电解质、肝肾功能以及内生肌酐清除率(creatinine clearance rate,Ccr)的变化.结果:治疗后患者血常规、电解质无明显改变,大多数患者BUN和SCr较治疗前下降,而Ccr升高,总有效率达65.6%.结论:中西医结合疗法可有效逆转慢性肾功能不全患者伴发急性肾功能减退时肾功能的恶化.     

Paired kidney analysis of tacrolimus and cyclosporine microemulsion-based therapy in Chinese cadaveric renal transplant recipients

Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation. Most of the published data used whole blood trough levels for drug monitoring. However, the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve (AUC(0-12)) allowed better prediction of drug exposure. Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were randomized to receive either tacrolimus-based (n = 33) or cyclosporine microemulsion (Neoral)-based therapies (n = 33). Abbreviated AUC(0-12) was used for drug monitoring and dose titration. Mean follow-up duration was 2.8 +/- 2 years. The patient and graft survival were comparable. Fewer incidence of acute rejection was observed in tacrolimus group (15% vs. 27.3%) though the difference was not significant (P = 0.23). The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients. Prevalence of hypertension, post-transplant diabetes mellitus, infection, and malignancy were similar in both groups. Prevalence of hypercholesterolemia (11/33 vs. 4/33) and gum hypertrophy (6/33 vs. 1/33) was more common in cyclosporine-treated patients (P = 0.04 in both parameters). This was the first prospective, randomized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients.     

Human Renal Allograft Rejection Despite the Absence of Allogeneic Passenger Leukocytes

Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression.