Chi-Hung Cheng

Long-Term Impact of Hepatitis B, C Virus Infection on Renal Transplantation

Chronic liver disease and its complications are major problems in renal transplant recipients. Our aim was to elucidate the influence of hepatitis B, C virus infection on the long-term outcome of renal transplantation. Four hundred and seventy-seven patients who received renal transplantation between January 1984 and December 1999, and who were followed up at our hospital were enrolled. HBsAg was detected by the RIA method and anti-HCV Ab was assayed by the second-generation RIA kit. SGOT/ SGPT were checked every 3 months. Hepatoma was diagnosed by dynamic CT scan, elevated α-fetoprotein, hypervascularity by angiography and confirmed by pathological examination. The prevalence of HBV, HCV, coinfected HBV/HCV was 9.9% (n = 47), 28.5% ( n = 136), 3.1% (n = 15), respectively. The incidences of hepatoma in the HBV–/HCV–, HBV–/HCV+, HBV+/HCV–, HBV+/HCV+ groups were 1.4% (n = 4), 4.4% (n = 6), 6.4% (n = 3), 6.7% (n = 1), respectively (p = 0.114). The incidences of liver cirrhosis/hepatic failure were 3.2% (n = 9) , 6.6% (n = 9) , 21.3% (n = 10) , 20% (n = 3), respectively (p < 0.001). The frequencies of chronic liver disease were 10.4% (n = 29) , 45.6% (n = 62) , 66% (n = 31) , 80% (n = 12), respectively (p < 0.001). Patient and graft survival rates were lower in the HBV-infected group than in the other groups. Cox regression analysis revealed that HBV infection is likely an independent risk factor for patient mortality although the statistical significance was only borderline. Patients with HBV as well as HCV infection were not at risk of graft loss according to this model of analysis. Patients with HBV infection showed higher incidences of hepatoma, hepatic failure, graft failure and death. Therefore, HBV-infected patients who are candidates for renal transplantation should be carefully evaluated. It seems that HCV infection has little influence on the outcome of renal transplant recipients. A longer period of follow-up is needed to clarify the impact of HCV on renal transplant recipients.

Lower Variability of Tacrolimus Trough Concentration After Conversion From Prograf to Advagraf in Stable Kidney Transplant Recipients

Backgrounds. Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation. Methods. The aim of this study is to prospectively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf. Results. The mean age of 129 patients was 51.3±12.1 years. The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation. The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion. Only six patients increased daily dose by 16.7% to 25% to maintain target levels. The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf; it was 4.9±1.5 ng/mL on the seventh day (P<0.001) and 5.4 to 5.5 ng/mL at 1 to 6 months (P<0.05). Forty-one (31.8%) patients have reduced C0 of more than 25% on the seventh day. The percent coefficient of variation of tacrolimus C0 more than 22.5% before conversion is associated with higher risk of reduced C0 after conversion (P<0.05). Compared with before conversion, less kidney transplant recipients have percent coefficient of variation more than 22.5% after conversion (3.1% vs. 17.4% with P<0.01). Conclusions. The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0. The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf.

Prevalence of subclinical cryoglobulinemia in maintenance hemodialysis patients and kidney transplant recipients

We studied the prevalence and the clinical spectrum of cryoglobulinemia (Cryo) among 101 maintenance hemodialysis (HD) patients and 148 kidney transplant (KT) recipients, with or without chronic hepatitis C virus (HCV) infection. Cryo was present in 32% (16 of 50) of the HCV-positive HD patients, 5.9% (3 of 51) of the HCV-negative HD patients, 37.8% (28 of 74) of the HCV-positive KT recipients, and 27% (20 of 74) of the HCV-negative KT recipients. Cryoprecipitate in 56.3% (9 of 16) of the HCV-positive Cryo HD patients and 53.8% (14 of 26) of the HCV-positive Cryo KT recipients contained HCV-RNA. Interestingly, the cryocrit values among HD and KT patients were much lower than these in other reports on nonrenal failure cases. Also, the cryoglobulinemic syndrome (with purpura, arthralgia, etc.) in HD and KT patients with Cryo were not common (Tables 1 and 2). There was not correlation between Cryo and age,sex, and liver function. Only longer duration of end-stage renal disease was noted in these patients. In addition, we suggested that KT patients are more susceptible to having Cryo. Further studies are necessary to better define whether any other subclinical viral or nonviral chronic infection may induce Cryo in HCV-negative KT recipients.

Use of Pulsed-Field Gel Electrophoresis in the Analysis of Recurrent Staphylococcus aureus Infections in Patients on Continuous Ambulatory Peritoneal Dialysis

Background/Aim: The purpose of this study was to evaluate pusled-field gel electrophoresis (PFGE) for distinguishing between relapse and reinfection of Staphylococcus aureus infections in patients on continuous ambulatory peritoneal dialysis (CAPD). Methods: Between July 1993 and May 1997, 4 patients with recurrent CAPD-associated infections caused by S. aureus we enrolled in this study. There were nine episodes of peritonitis, one episode of temporary double lumen catheter infection, and one episode of Hickman catheter infection. A total of eleven S. aureus isolates were collected from peritoneal fluid (n = 9) and blood (n = 2). PFGE typing was applied. Results: In our study, from PFGE typing, the 11 S. aureus isolates were classified into seven patterns. Antibiogram profiling classified only four patterns. Patient A had a reinfection by another strain of S. aureus, and patient B had three episodes of peritonitis caused by the same strain of S. aureus due to exit site infections. Patient C had two episodes of CAPD peritonitis caused by two different strains, respectively. Patient D had four episodes of S. aureus infection (three CAPD peritonitis and one bacteremia); the first two episodes of peritonitis were caused by an identical strain of S. aureus, whereas the subsequent two infections were caused by other organisms. Conclusion: PFGE has a high discriminatory power and can be an assistant method to antibiogram profiling for distinguishing relapse from reinfection in CAPD-associated peritonitis.

Peritoneal-dialysis-associated penicillium peritonitis.

Accessible online at: www.karger.com/journals/ajn Dear Sir, Fungal peritonitis carries a high mortality and morbidity rate and is a significant cause of treatment failure [1] in patients on continuous ambulatory peritoneal dialysis (CAPD). We report a case of unusual fungal peritonitis caused by Penicillium sp. in a 56year-old female undergoing CAPD. Penicillium are blue-green, saprophytic molds with several hundred species identified, but only a few are known to cause human diseases. The other 4 cases of Penicillium peritonitis reported in the English language literature are also reviewed. A favorable outcome for Penicillium peritonitis may be feasible if the catheter is removed early after identification of this organism followed by antifungal therapy. A 56-year-old female with diabetic nephropathy in the uremic stage who had received CAPD with a Tenckhoff catheter for 18 months without experience of peritonitis before was admitted to Taichung Veterans General Hospital with turbid peritoneal effluent and a decreased fluid amount for about 2 weeks. She had presented with abdominal pain for 2 weeks and had received intraperitoneal antibiotic therapy with cefazolin and gentamicin at another hospital for 1 week prior to this admission. The color of the peritoneal effluent became clear once but returned to cloudy again. On the day of admission, she did not have abdominal pain but low-grade fever could be noticed. The

Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy

A quantitative scoring method was designed to assess the extent of muscle damage. Technetium-99m pyrophosphate (99mTc-PYP) scintigraphy was performed for 9 patients experiencing crush injury in the Chichi (Taiwan) earthquake. The magnitude of muscle uptake of 99mTc-PYP was graded as follows: grade 0, less than bone radioactivity (BRA); grade 1, equal to BRA; grade 2, higher than BRA; or grade 3, greatly higher than BRA. The area of muscle injury was estimated according to the rule of nines. The sum of the muscle injury size multiplied by its corresponding grading was defined as the anterior or posterior score according to the anterior or posterior images. Each image was interpreted by two physicians and average anterior and posterior scores were calculated. The muscle score was defined as the geometric mean of the average anterior and posterior scores. Significant correlations were obtained between the muscle score and duration of time trapped (r = 0.868, p < 0.01), peak serum creatine kinase level (r = 0.866, p < 0.01), peak serum phosphorus level (r = 0.877, p < 0.01) and number of hospital days (r = 0.875, p < 0.01). A negative correlation between the muscle score and blood pH (r = –0.706, p < 0.01) was also observed. We concluded that this scoring method may be used as an adjunct for evaluating the locations of trauma and the severity of crush syndrome, and for predicting the duration of hospital stay.

Possible Mechanism by Which Rapamycin Increases Cyclosporine Nephrotoxicity

It is well known that the combination of cyclosporine A (CsA) with rapamycin produces serious nephrotoxicity. Herein we suggest a mechanism by which rapamycin increases CsA nephrotoxicity. Previously, we demonstrated that activation of Akt/protein kinase B protects against cyclosporine nephrotoxicity and prevents apoptosis. Recently, it has been shown that Akt phosphorylation activates mammalian target of rapamycin (m-TOR) and inhibits programmed cell death including apoptosis and autophagy. Akt is believed to be an importance factor for cell survival. In theory, blockade of the Akt pathway through inhibition of m-TOR may increase cyclosporine-induced apoptosis. We added cyclosporine and rapamycin to cultures of ER52K proximal renal tubule cells, leading to a significantly decreased survival rate. The nephrotoxicity was associated with increased apoptosis by cleavage of caspase-3 and decreased phosphorylation of m-TOR and AktSer473, findings that support this hypothesis. This nephrotoxic effect may explain the clinical finding that patients treated with rapamycin alone exhibited better renal function than those treated with concomitant cyclosporine therapy.

Consultants for the American Journal of Nephrology 1997

Consultants for the American Journal of Nephrology 1997 Abrass, Christine Adler, Sharon Agodoa, Lawrence Akmal, Mohammad Anderson, Sharon Andreucci, Vittorio Avram, Morel Bakris, George Balow, James Bennette, William Boswell, William Breyer, Julia Langman, Craig Levin, Nathan Limb, Victoria Maroni, Bradley Martinez-Maldonado, Manuel Matthew, Weir R. Mitch, William Mushnick, Robert Nissenson, Allan Nolph, Karl Nosrati, Saeid