Isolated Crystalloid Podocytopathy With Focal Segmental Glomerulosclerosis in Renal Allograft: An Unusual Presentation of Post-Transplant Monoclonal Gammopathy of Renal Significance-A Case Report.

BACKGROUND: Monoclonal gammopathy of renal significance denotes a spectrum of hematologic disorders that cause direct or indirect renal damage. CASE PRESENTATION: A 51-year-old man had received a living-donor kidney transplant from his wife in 2008. He had gradual increased proteinuria 4 years later. His renal biopsy results revealed cytoplasmic crystalloid inclusions in the podocytes. No crystalloid inclusion was found in other renal cells. Despite that immunofluorescent examination failed to show light-chain deposition, the serum immuno-electrophoresis revealed monoclonal immunoglobulin-Gκ. Bone marrow biopsy showed interstitial infiltration of plasma cells of approximately 10%. A follow-up renal biopsy was performed in 2016. Light microscopy showed focal segmental glomerulosclerosis. The immunofluorescent examination remained negative for light chain, but κ-light chain could be demonstrated after antigen retrieval. Similar to previous biopsy results, cytoplasmic inclusions were found only in podocytes without involving other renal cells. CONCLUSIONS: To the best of our knowledge, this is the first report of monoclonal gammopathy of renal significance presenting as isolated crystalloid podocytopathy in the allograft kidney. The mechanism of preferential podocyte deposition of crystalloid immunoglobulin remains unclear. The inherent features of crystalloid podocytopathy may mislead the pathologic diagnosis.

How to Improve the Positive Predictive Value of Urinary Decoy Cell Surveillance for Polyomavirus BK-Associated Nephropathy in Kidney Transplant Patients.

BACKGROUND: Polyomavirus BK-associated nephropathy (BKVN) has been a serious problem after kidney transplantation. Detection of urinary decoy cells (UDCs) and assessment of polyomavirus BK nucleic acids by polymerase chain reactions (PCRs) are currently used, noninvasive tests. PCRs have better positive predictive value (PPV) but higher cost and lower accessibility. This study investigated ways to improve the PPV of UDCs for BKVN prediction. METHODS: From 2000 to 2013, kidney transplant recipients with sustained UDCs for more than half a month and who had received allograft biopsies were enrolled. We analyzed the PPV of UDCs for BKVN with 2 variables: (i) the percentage changes in serum creatinine (SCr) levels and (ii) the duration of sustained UDCs by receiver operating characteristic (ROC) curve analysis; we predicted the percentage changes in SCr levels with the corresponding PPV using a linear regression model. RESULTS: BKVN was diagnosed in 26 of 68 enrolled patients. The percentage changes in SCr levels significantly deteriorated in the BKVN group during 1-2 months of UDC positivity. According to ROC curve analysis, percentage changes in SCr levels had a significant discriminating power for BKVN during 1-1.5 month, and if the percentage changes in SCr levels were >19%, the PPV of UDCs for BKVN was 50%. CONCLUSIONS: An UDC surveillance program is a judicious strategy to predict BKVN in kidney transplant patients, particularly when graft renal function shows deterioration after 1 month of UDC positivity.

New-onset diabetes mellitus in cyclosporine-treated organ transplant patients in Taiwan: interim analysis (6 months) of postmarketing surveillance.

Posttransplant new-onset diabetes mellitus (NODM) is an important complication among patients receiving immunosuppressants. It has a considerable impact on chronic allograft dysfunction. Calcineurin inhibitors have been implicated in the development of posttransplant NODM. Since high-risk candidates also undergo transplantation, prevention and control of posttransplant NODM is important. A 3-year postmarketing surveillance study is currently underway in Taiwan to evaluate the incidence and risk factors leading to development of NODM among de novo and maintenance solid-organ transplant patients receiving cyclosporine (CsA)-based immunosuppressive therapy. Concomitant therapy consisted of basiliximab, mycophenolate mofetil or enteric-coated mycophenolate sodium, and corticosteroids. Diabetes was diagnosed according to the American Diabetes Association criteria. This 6-month protocol-defined interim analysis included 101 patients (84 de novo, 17 maintenance) who received renal (n = 77), liver (n = 13), or heart (n = 11) transplantation. At the end of 6 months, 8/101 (7.92%) patients experienced NODM. The mean time to NODM was 3.05 months. No significant difference was observed between NODM and non-NODM patients for risk factors: age, body mass index, blood pressure, gender, high-density lipoproteins/triglycerides hdl/tg, and anti-hepatitis C virus. The composite endpoint of biopsy-proven acute rejection, graft loss, or death was reached in four patients, with a mean time to event of 3.81 months. Infections were noted in 34 subjects but, no malignancies. Among 389 adverse events reported in 91 patients (90.1%), the majority were of mild to moderate severity. Two deaths were reported: heart transplant recipients with acute rejection and cytomegalovirus meningitis with respiratory failure. Long-term enrollment with follow-up evaluation of these NODM patients up to 3 years will help evaluate the NODM incidence rates and exact graft survival and overall survival rates of CsA-treated transplant patients in Taiwan.

Results of kidney transplantation from high-terminal creatinine donors and the role of time-zero biopsy.

BACKGROUND: Deceased-donor kidney transplantation (DDKT) from high-terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. METHODS: From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. RESULTS: Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times (P = .011) but a higher incidence of delayed graft function after transplantation (P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. CONCLUSIONS: With a time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival.

Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial.

OBJECTIVE: To test in a prospective randomized study the hypothesis that use of thromboelastography (TEG) decreases blood transfusion during major surgery. MATERIAL AND METHODS: Twenty-eight patients undergoing orthotopic liver transplantation were recruited over 2 years. Patients were randomized into 2 groups: those monitored during surgery using point-of-care TEG analysis, and those monitored using standard laboratory measures of blood coagulation. Specific trigger points for transfusion were established in each group. RESULTS: In patients monitored via TEG, significantly less fresh-frozen plasma was used (mean [SD], 12.8 [7.0] units vs 21.5 [12.7] units). There was a trend toward less blood loss in the TEG-monitored patients; however, the difference was not significant. There were no differences in total fluid administration and 3-year survival. CONCLUSION: Thromboelastography-guided transfusion decreases transfusion of fresh- frozen plasma in patients undergoing orthotopic liver transplantation, but does not affect 3-year survival.

Evaluation of cortical perfusion in renal transplants: application of quantified power Doppler ultrasonography.

Perfusion of renal transplants may be altered by various pathological conditions. This study assessed cortical perfusion of renal transplants during acute rejection episodes using power Doppler quantification. Forty-eight renal transplant patients with clinical indications for biopsy were included in this study. Power Doppler ultrasonography (US) of these renal transplants was performed prior to biopsy. Power Doppler image intensity in the proximal outer cortex of renal transplants was quantified by image analysis software. The results of power Doppler quantification were compared with the clinical data and histological findings. Biopsies were classified into three groups based on Banff diagnostic categories: group 1 (no acute rejection; 26 patients), group 2 (acute cell-mediated rejection alone; 12 patients), and group 3 (acute antibody-mediated rejection with/or without acute cell-mediated rejection; 10 patients). The power Doppler intensity of the outer renal cortex was 1.98 +/- 1.50 dB for group 1, 1.38 +/- 0.86 dB for group 2, and 0.81 +/- 0.66 dB for group 3. Statistically, there was a significant difference between group 1 and group 3 (1.98 vs 0.81 dB, P = .01) but not between group 1 and group 2 (1.98 vs 1.38 dB, P = .34). In conclusion, the status of cortical perfusion of renal transplants can be determined noninvasively by quantified power Doppler US. Accordingly, acute antibody-mediated rejection is associated with significantly decreased cortical perfusion, which, we propose, is due to this distinct pathological process.

Hepatocellular carcinoma after renal transplantation: the long-term impact of cirrhosis on chronic hepatitis B virus infection.

Hepatocellular carcinoma (HCC) is the most common posttransplantation malignancy in hepatitis B virus (HBV) endemic areas. The aim of this study was to review the significant effect of liver cirrhosis on the outcome of renal allograft recipients with chronic hepatitis B. We performed a retrograde analysis of the clinical presentations of 66 hepatitis B surface antigen-positive kidney allograft recipients during the past 25 years with a mean follow-up of 76 months. Seven patients were diagnosed with HCC. The patients were subgrouped into cirrhotic versus noncirrhotic liver cohorts. Among renal allograft recipients with HBV infection, patients with cirrhotic livers had a higher risk of HCC (P = .003) and mortality (P = .025) than those with a noncirrhotic liver. The outcome was poor among the cirrhotic liver group. Pretransplantation liver biopsy may be indicated for the recipient candidate with HBV infection. Liver cirrhosis may be an exclusion criterion for the renal transplant waiting list due to the high incidence of HCC and the poor patient survival.

ENDO-GIA staplers for side-to-side anastomosis of veins.

OBJECTIVE: To study the application of ENDO-GIA staplers for the side-to-side anastomosis of veins. MATERIALS AND METHODS: An animal study was conducted. Five dogs received side-to-side anastomosis of allograft IVC by ENDO-GIA staplers (Group 1). In addition, five received the same operation with right renal vein reimplantation to allograft IVC (Group 2). Five dogs, receiving the same operation as in Group 1 using polypropylene sutures (control group, Group 3). An autopsy was performed if the dogs survived more than 8 weeks. RESULTS: The IVC anastomosis remained patent in four subjects (80%) for Group 1, in five subjects (100%) for Group 2 and in four subjects (80%) for Group 3. CONCLUSIONS: From the results of our experiment, ENDO-GIA staplers can be considered for use in the side-to-side anastomosis of large veins such as piggyback cavacaval side-to-side anastomosis in cadaveric orthotopic liver transplantation (OLT) or side-to-side splenorenal shunt in portal hypertension.

Antioxidant supplementation may improve renal transplant function: a preliminary report.

Dysfunction of the renal graft may not only be due to rejection but also other causes such as ischemia and reperfusion injury and calcineurin inhibitor nephrotoxicity. Antioxidant free radical scavengers may decrease oxidative stress and lipid peroxidation. Previous animal studies suggest that vitamins C (ascorbic acid) and E (alpha-tocopherol) are both strong antioxidants, that decrease oxidative stress caused by ischemia-reperfusion injury and calcineurin inhibitor nephrotoxicity. But there have been only limited reports about clinical efficacy. We report five cases supplemented with vitamin C (500 mg per day), vitamin E (500 mg per day), or both. After a 1- to 3-month prescription, the serum creatinine level decreased more than 20% from the original value. Interestingly, one patient had this experience: he ceased vitamin E for 1 month due to noncompliance. The serum creatinine level increased more than 50%. When he took vitamin E again, his serum creatinine level declined and returned to the previous level. From our limited experience, antioxidant supplementation with vitamin C or E may improve renal transplant function, especially in grafts donated from marginal donors.

Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome.

AIM: The prognosis of patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection varies widely. This study analyzed long-term survival and prognostic factors of patients with recurrent HCC after hepatectomy. METHODS: From July 1991 to December 2000, 623 patients underwent hepatic resection for HCC. Of those, 347 (56.5%) patients had tumour recurrence, and 286 patients with follow-up time more than 24 months after recurrence were enrolled. Twenty-seven clinicopathologic factors underwent both univariate and multivariate analysis. RESULTS: Of these 286 patients, survival times after tumour recurrence were mean 672+/-619 days; median 468 days; and, range 10-3753 days. The overall 1-, 3-, 5-, and 10-year post-recurrence survival rates were 61.5, 33.4, 18.2, and 9.0%, respectively. Seventy (24.5%) patients were alive at the time of study, and 10 of the 34 patients who underwent re-resection were disease-free. By Cox regression analysis, multiple initial tumours (relative risk (RR) 1.428), recurrent multiple (RR 1.372), extrahepatic recurrence (RR 2.434), recurrent tumour size >2 cm (RR 1.926), post-hepatectomy period until recurrence <1 year (RR 1.769), and non-resectional treatment of recurrent tumours (RR 3.527) were independent prognostic factors for post-recurrent survival rates. CONCLUSIONS: In patients with recurrent HCC after hepatectomy, both initial and recurrent tumour factors influenced their prognosis. Early detection of recurrent tumours is important. Re-resection correlated with better post-recurrent survival rates.

Reliability of contemporary radiology to measure tumour size of hepatocellular carcinoma in patients undergoing resection: limitations and clinical implications.

BACKGROUND: Preoperative radiology has been widely used to detect and measure hepatocellular carcinoma (HCC). However, its accuracy and reliability are unclear. This study aimed to assess the ability of current radiology to measure tumour size in patients undergoing resection. METHODS: We evaluated 212 HCC patients undergoing curative resection. Tumour size measured in the pathological examination was correlated with that obtained in preoperative ultrasound (US) and contrast-enhanced dynamic computed tomography (CT). Accuracy and association with tumour recurrence were investigated. RESULTS: The mean size of the tumour was 4.5 +/- 2.6 cm and was accurate in both US and CT in only 6 (3%) patients. Cirrhosis (P = 0.015), absence of tumour stain (P = 0.002) and small (< or = 4 cm) tumour (P < 0.001) were the significant factors associated with size deviation using both US and CT. Ninety-four (44%) patients developed tumour recurrence within 17 +/- 11 months of resection. Recurrence rate was 52%, 52% and 67% in patients with underestimation in US (relative risk [RR]: 2.0, 95% confidence interval [CI]: 1.2-3.4, P = 0.01), CT (RR: 2.1, 95% CI: 1.1-4, P = 0.022) and both modalities (RR: 2.5, 95% CI: 1.4-4.2, P = 0.001), respectively, compared to 30% recurrence in patients with accurate estimation of tumour size. CONCLUSION: The accuracy of radiology in measuring tumour size was poor, and may lead to inappropriate treatment. The finding that underestimation of tumour size was associated with a higher tumour recurrence rate is consistent with the hypothesis that HCC may recur from pre-existing tumour foci which could not be identified from the current imaging modalities.

IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection.

In the present study we have tried to establish the role of IL-17 in subclinical renal allograft rejection. In this animal model, renal grafts from BN (RT1n) were transplanted heterotopically into LEW (RT1l) rats. As controls, LEW grafts were transplanted into LEW rats. The histopathological examination demonstrated that the changes in the allograft kidney on day 2 were similar to those ranked as borderline changes according to the Banff classification scale. On day 2, the serum level of blood urea nitrogen (BUN) and creatinine were the same as on day 1. The examination of allograft cytokines mRNA showed that IL-17 mRNA expressed earlier on the second postoperative day, peaked at day 5, and then declined, becoming almost undetectable at day 9, when most rats died. IL-17 antigen was also proven, by histochemical staining, to be expressed early, however we could not find the same early appearance on other Th1/Th2 cytokines. In human renal biopsy samples, the IL-17 antigen could be found scattered around in the borderline changed rejected renal allografts without evidence of a serum creatinine increase, but was undetectable both in normal controls and in renal transplant tissue without signs of rejection. IL-17 mRNA was detected in the mononuclear cells of the urinary sediment of patients suffering from borderline subclinical rejection. From the above results we can hypothesize that IL-17 could serve as a predictive parameter for borderline subclinical renal allograft rejection in the future.

Clinicopathologic and prognostic differences between patients with hepatitis B- and C-related resectable hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors in the development of hepatocellular carcinoma (HCC). This study examined the clinicopathologic and prognostic differences in patients with hepatitis B- and C-related resectable HCC. METHODS: A total of 270 HCC patients who underwent hepatic resection were enrolled. Among these patients, 211 were positive for hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C virus antibody (anti-HCV). The clinical manifestations, pathologic features, and treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients were significantly younger, had a higher familial incidence of HCC, larger tumor size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV positive had worse liver function and a higher incidence of history of blood transfusion. DNA flow cytometric analysis revealed significantly more proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly lower overall survival rate than anti-HCV-positive patients (p = 0.018). CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable survival rate after tumor resection than anti-HCV-positive HCC patients. This survival difference might have been related to the relatively advanced stage of disease and the higher proliferative activity of the non-tumor part of the liver in HBsAg-positive HCC patients.

Kidney transplantation in patients with chronic hepatitis B virus infection: is the prognosis worse?

The impact of hepatitis B virus (HBV) infection on the long-term outcome of kidney transplant patients is controversial. A total of 34 chronic hepatitis B surface antigen (HBsAg) carriers among 143 renal allograft recipients were identified in this study (mean follow-up period: 5.6+/-3.3 years; range: 1-13 years). During the follow-up, one HBsAg-positive recipient with preexisting cirrhosis died of liver failure, and seven (21%) others developed serious HBV-related complications (four fulminant hepatitis, two hepatocellular carcinoma, one cirrhosis), and four died. Although HBsAg-positive recipients had a higher rate of liver-related complications and deaths than HBsAg-negative recipients did, there were no significant differences in the long-term graft and patient survival between the two groups. The survival rates, liver-related complications, and deaths in HBsAg-positive allograft recipients and 28 HBsAg-positive uremic patients under dialysis were similar. In conclusion, HBV infection is not a contraindication to kidney transplantation. However, pretransplant candidates should be warned of potentially serious liver-related complications.

Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma.

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.

Better post-resectional survival in female cirrhotic patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is notably more prevalent in male. The purpose of this study was to assess the surgical results in male and female cirrhotic patients. METHODOLOGY: The surgical outcomes of 129 hepatocellular carcinoma patients with cirrhosis, including 109 males and 20 females, who had undergone hepatic resection were studied. The clinical, histologic features, DNA ploidy and proliferative phase fraction of tumor and cirrhotic liver were compared between male and female patients. RESULTS: Female patients had significantly lower incidences of history of smoking (5.6% vs. 52.9%, P < 0.001), alcohol intake (5.6% vs. 42.3%, P = 0.003) and hepatitis B surface antigen positivity (47.1% vs. 73.5%, P = 0.028) than male. Cell-cycle analysis of tumor part revealed female had a significant lower G2M phase fraction (3.4%) than male (5.7%) (P = 0.027). The 1-, 3-, and 5-year disease-free survival rates in male and female patients were 65.5% and 88.2%, 36% and 64.4%, and 29.7% and 64.4%, respectively. Female patients had a significantly better disease-free survival than male (P = 0.034, log-rank test). CONCLUSIONS: Female hepatocellular carcinoma with cirrhosis had lower incidences of hepatitis B surface antigenemia, alcohol abuse and lower DNA postsynthetic phase fraction in tumor tissue than male. Consequently, female hepatocellular carcinoma with cirrhosis had better survival than male.

Perioperative safety and prognosis in hepatocellular carcinoma patients with impaired liver function.

BACKGROUND: The benefits of liver resection for hepatocellular carcinoma (HCC) patients with concomitant impaired liver function were often considered questionable because of poor postoperative prognosis. This study will clarify whether an acceptable operative risk exists and whether limited resection will compromise the outcomes of these patients. STUDY DESIGN: Between July 1991 and December 1996, a total of 168 patients with HCC who underwent hepatectomies were enrolled and divided into normal (group A) and impaired (group B) liver function groups according to the value of indocyanine green retention rate at 15 minutes. Clinical features, surgical related features, pathologic features, and disease-free and overall survivals were compared between the groups. RESULTS: Operative morbidity and mortality in group A were 27.3% and 1.6%, and in group B were 40.0% and 2.5%, respectively (p = 0.129 and 0.506). Disease-free survival and overall survival at 5 years in group A were 43.2% and 59.6%, respectively, and in group B they were 30.6% and 56.8%, respectively (p = 0.607 and 0.378). CONCLUSIONS: Limited liver resection is safe and provides favorable prognosis in HCC patients with concomitant impaired liver function.

Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma.

OBJECTIVE: To evaluate the clinical significance of preoperative serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in patients with resectable hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: IL-10 is an immunosuppressive factor and IL-6 is a multifunctional cytokine that plays a role in host defense mechanisms. Both have been reported to be related to the disease prognosis in some human solid tumors. Their role in human HCC has not been investigated. METHODS: Preoperative serum samples of 67 patients with HCC who underwent potentially curative resection and 27 normal healthy donors were assayed. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay. The clinical significance of serum IL-10 and IL-6 was evaluated and compared with conventional clinicopathologic factors. RESULTS: Levels of IL-10 and IL-6 were significantly higher in patients with HCC than in healthy subjects. There was no correlation between IL-10 and IL-6 levels. Tumor resection resulted in a decrease in IL-10 and IL-6 levels. On univariate analysis, patients with high IL-10 levels had a worse disease-free survival, but IL-6 levels had no correlation with the disease-free survival. Multivariate analysis identified IL-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors. CONCLUSIONS: In patients with HCC, the preoperative serum IL-10 level is related to the clinical outcome. IL-10 may play an important role in the progression of HCC.

Impact of hepatitis B and C virus infection on the outcome of kidney transplantation in Chinese patients.

BACKGROUND: There has been improvement in kidney transplantation over the years; however, the impact of hepatitis B and C virus (HBV, HCV) infection on the long-term outcome of kidney transplant is still controversial. METHODS: A total of 113 patients who received renal allografts from 1986 to 1998 were analyzed. Nine were positive for both hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) (Group 1), 20 were HBsAg-positive and anti-HCV-negative (Group 2), 30 were HBsAg-negative and anti-HCV-positive (Group 3) and 54 were negative for both markers (Group 4). The outcome and survival were compared among the four groups of patients. RESULTS: The mean follow-up period was 5.1 +/- 3.2 years (range, 0.5-13 years) for all patients. Group 2 patients had significantly higher liver-related complications (35% vs 0%, p < 0.0001) and liver-related deaths (20% vs 0%, p = 0.004) than did Group 4 patients. Among all, four HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three (Group 2) of the patients who died were seropositive for hepatitis B e antigen and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. The remaining patient (Group 1) had evidence of superinfection of HCV. Liver cirrhosis occurred in one, two and one patient in Groups 1, 2 and 3, respectively, and hepatocellular carcinoma occurred in two and one patient in Groups 2 and 3, respectively. Despite high liver-related mortality in HBV-infected patients, paradoxically, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with a poor prognosis of survival as determined by Cox regression analysis. CONCLUSIONS: HBV or HCV infection is not a contraindication to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in HBV- and/or HCV-infected patients after kidney transplantation.

Renal allograft dysfunction associated with rifampin-tacrolimus interaction.

OBJECTIVE: To report an interaction between tacrolimus and rifampin with subsequent adverse effects on renal allograft function. CASE SUMMARY: A 61-year-old Chinese man received a cadaveric renal transplant in 1991. Progressive deterioration of allograft function developed during the following six years while the patient was receiving cyclosporine and prednisolone. In January 1998, tacrolimus was substituted for cyclosporine for late biopsy-proven graft rejection, with target trough blood concentrations between 5 and 8 ng/mL. After conversion, serum creatinine fell to 2.0 mg/dL; the nadir was reached within one year. At the same time, rifampin was instituted for controlling tuberculosis and empiric fluconazole was discontinued. Twelve days later, the patient's serum creatinine concentration rose to 2.9 mg/dL and tacrolimus concentration fell to 1.5 ng/mL, along with oliguria. These findings suggested acute rejection, which was successfully reversed by steroid therapy. However, more than a tenfold increase in the tacrolimus dosage was required to maintain the same concentrations during subsequent months, accompanied by an increase in serum creatinine (from 2.0 to 2.6 mg/dL) and decrease in urine excretion. Biopsy at this time demonstrated acute rejection (Banff I), chronic allograft nephropathy (Banff II), and suspected tacrolimus nephrotoxicity. After unsuccessful methylprednisolone recycling, mycophenolate mofetil was introduced to control rejection and facilitate reduction of the tacrolimus dosage to minimize its nephrotoxicity. CONCLUSIONS: As a potent CYP3A4 isoenzyme inducer, rifampin coadministration caused the abrupt decrease in tacroiimus blood concentrations, leading to an approximate tenfold increase in its daily dose, which may be important to subsequent allograft dysfunctions.