Gastrointestinal stromal tumors in kidney transplant recipients: Report of two cases and literature review.

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal gastrointestinal neoplasms. However, GISTs occurring in kidney transplant recipients, including their treatment and outcome, are rarely described in literature. We hereby report two kidney transplant recipients with GISTs. Our first patient was diagnosed with high-risk epithelioid gastric GIST 2 years after kidney transplant. He received everolimus after resection and remained disease-free for 2 years before liver metastasis was confirmed. Imatinib therapy was planned but he died of fulminant pneumonia shortly. Our second patient was diagnosed with spindle cell GISTs in the mesentery 1 year after kidney transplant. Only partial response was obtained with imatinib as new lesions continued to develop. Withdrawal of cyclosporine and introduction of sirolimus resulted in complete shrinkage of existing tumors and no new lesions. He remained disease-free for more than 10 years. Combination therapy consisting of imatinib and inhibitors of mammalian target of rapamycin (mTORi) seems to be safe and effective in kidney transplant recipients. However, therapeutic drug monitoring of mTORi is essential to avoid nephrotoxicity. Further trials addressing the optimal dosage of imatinib and mTORi in kidney transplant recipients are recommended.

Peritoneal mesothelial cell culture and biology.

The peritoneal mesothelium is composed of an extensive monolayer of mesothelial cells that lines the body's serous cavity and internal organs and was previously thought to act principally as a protective nonadhesive lubricating surface to facilitate intracoelomic movement. With the introduction of peritoneal dialysis over three decades ago, there has been much interest in the cell biology of peritoneal mesothelial cells. Independent studies have highlighted specific properties of the peritoneal mesothelial cell, including antigen presentation, regenerative properties, clearance of fibrin; synthesis of cytokines, growth factors, and matrix proteins; and secretion of lubricants to protect the tissue from abrasion, adhesion, infection, and tumor dissemination. It is now evident that the mesothelium is not merely a passive membrane but, rather, a dynamic membrane that contributes substantially to the structural, functional, and homeostatic properties of the peritoneum. Since peritoneal mesothelial cells in culture possess immunohistochemical markers identical to mesothelial stem cells, the culture of mesothelial cells offers researchers an essential tool to assess their morphologic, structural, and functional properties. This review will discuss current procedures to isolate peritoneal mesothelial cells from human omental specimens, animal sources, and spent dialysate. Furthermore, the functional and morphologic properties of mesothelial cells are discussed, together with the potential use of mesothelial cell culture in research and clinical applications.

Risk factors and outcomes of extended-spectrum beta-lactamase-producing E. coli peritonitis in CAPD patients.

OBJECTIVE: To determine the risk factors and outcomes of peritonitis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Episodes of E. coli CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed. Demographic data, underlying medical conditions, recent use of gastric acid inhibitors (including H2 antagonist and proton pump inhibitor), recent antibiotic therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of the E. coli isolated, and clinical outcomes were examined. RESULTS: Over a 10-year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88 cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and gastric acid inhibitor were associated with the development of ESBL-producing E. coil peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs 13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure rate was higher in the ESBL-producing E. coli group, although the difference was not statistically significant (18.2% vs 3.9%, p = 0.12). CONCLUSION: Peritonitis caused by ESBL-producing E. coli is associated with worse clinical outcomes. The use of cephalosporins and gastric acid inhibitors may contribute to its development. Further studies are warranted to investigate and determine the predisposing factors for ESBL-producing E. coli peritonitis.

Minimal and optimal peritoneal Kt/V targets: results of an anuric peritoneal dialysis patient's survival analysis.

BACKGROUND: Residual renal clearance has been shown to be much more predictive of survival than peritoneal clearance. There has been little data to support a target level of peritoneal clearance. A retrospective study was therefore conducted to see how the peritoneal Kt/V had affected the survival of anuric patients in our center. METHODS: Over a period of 10 years, there were 150 peritoneal dialysis patients with documented anuria. Their survival was analyzed according to their baseline peritoneal Kt/V at the time of documentation of anuria and at the time of their latest altered peritoneal dialysis (PD) prescription (subsequent Kt/V). RESULTS: There were 90 females and 42 diabetics. The mean age and duration of dialysis were 57.7 +/- 14.7 and 44.1 +/- 31.3 months, respectively. The 2-year and 5-year survival rates were 88.7% and 66.7%, respectively. We found that patients with baseline peritoneal Kt/V below 1.67 had poorer survival after the documentation of anuria than those above [relative risk (RR) 1.985, P= 0.01], although the baseline Kt/V was not an independent risk factors in the whole group of patients. However, such effect was mainly observed in female patients. The survival was identical between those with Kt/V above or below 1.80 (P= 0.98). Among female patients, the group with baseline Kt/V 1.67 to 1.86 had the best survival, followed by those greater than 1.86 and lowest in those below 1.67 (P= 0.0016). For patients with baseline Kt/V below 1.80, those with subsequent Kt/V above 1.76 had better survival than those below (P= 0.033). CONCLUSION: Our data suggested that a negative effect of peritoneal Kt/V on survival is apparent at a level below 1.67 and there exists a limit of its effect at around 1.80. We suggested a minimal Kt/V target of 1.70 and an optimal target at 1.80 in anuric patients based on survival data. Prospective randomized study is required to confirm this finding.

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis.

Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamide followed by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated with less drug toxicity. Results from an extended long-term study, with median follow-up of 63 mo, that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented. Thirty-three patients were randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm, both in combination with prednisolone. More than 90% in each group responded favorably (complete or partial remission) to induction treatment. Serum creatinine in both groups remained stable and comparable over time. Creatinine clearance increased significantly in the MMF group, but the between-group difference was insignificant. Improvements in serology and proteinuria were comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up (P = 0.667). Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients (11 and nine patients relapsed, respectively) and between those with MMF treatment for 12 or >/=24 mo. MMF treatment was associated with fewer infections and infections that required hospitalization (P = 0.013 and 0.014, respectively). Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death (P = 0.062 by survival analysis). It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients.

Tuberculous infection in southern Chinese renal transplant recipients.

A retrospective study of the prevalence and pattern of tuberculosis among renal transplant patients in a single centre in southern China was performed. Twenty-three cases of tuberculosis were diagnosed among 440 patients between January 1991 and December 2002. There were 18 men and five women. The mean age of the patients was 39.3 +/- 13.4 yr. There were 13 living-related and 10 cadaveric renal transplants. The interval between renal transplantation and the development of tuberculosis ranged from 3 to 127 months with a median of 46 months. There were 18 cases of pulmonary tuberculosis, two cases of pulmonary plus laryngeal tuberculosis, two cases of disseminated tuberculosis, and one case of tuberculosis involving the urinary tract. Diagnosis was established by positive culture for Mycobacterium tuberculosis in 21 patients and response to empirical anti-tuberculosis treatment in two patients. The duration of symptoms before the diagnosis of tuberculosis was 27 +/- 12 d. The patients were treated with standard anti-tuberculosis drugs for 11 +/- 3 months. The anti-tuberculosis treatment was in general well-tolerated. Five patients developed transient hepatitis, three patients developed thrombocytopenia and five patients developed gouty arthritis. One patient died 2 months after initiation of anti-tuberculosis therapy. All other patients completed anti-tuberculosis treatment. No recurrence of tuberculosis was observed after a median follow-up of 90 months. We concluded that (i) tuberculosis is prevalent among southern Chinese renal transplant recipients; (ii) high index of suspicion for tuberculosis among renal transplant recipients is warranted to ensure early diagnosis and prompt initiation of treatment; and (iii) treatment with standard anti-tuberculosis drugs for an extended period of time is well-tolerated and is associated with favourable outcome.

Retroperitoneal leakage as a cause of ultrafiltration failure.

We report 3 patients on continuous ambulatory peritoneal dialysis (CAPD) who developed reversible ultrafiltration failure secondary to retroperitoneal leakage. The patients presented with pulmonary edema and fluid overload following a sudden onset of ultrafiltration failure on maintenance CAPD. There was no localized edema, suggesting peritoneal leakage in the abdominal wall or the perineum. Radiological examination showed no migration of the Tenckhoff catheter. Leakage of dialysate into the retroperitoneal space was only revealed by computed tomographic (CT) peritoneography. These patients were then treated with intermittent peritoneal dialysis twice weekly. After repeated CT peritoneography showing complete resolution of the leakage, they successfully resumed CAPD treatment 2 months later, without ultrafiltration problems. Our finding suggests that retroperitoneal leakage could be one of the uncommon, yet reversible, causes of acute ultrafiltration failure that can be diagnosed with CT peritoneography.

Management of hepatocellular carcinoma in renal transplant recipients.

BACKGROUND AND OBJECTIVE: In Hong Kong where hepatitis B virus (HBV) infection is endemic, hepatocellular carcinoma (HCC) accounts for 20% of all malignant transformations in renal transplant recipients. The aim of the present study was to review the management and outcome of HCC in renal transplant recipients at a specialized surgical center. METHOD: A retrospective analysis on the data collected prospectively in a tertiary referral center. RESULTS: From January 1991 to December 2002, five renal transplant recipients were diagnosed to have primary HCC and received treatment in our center. There were four men and one woman with a median age of 47 (range, 38-68) years. Four of them had cadaveric renal transplantation whereas one had live donor transplantation. All of them were HBV carriers. The median tumor size was 3.5 cm (range, 1.8-8 cm). All tumors, except one, were diagnosed in sub-clinical stage by surveillance serum alpha-fetoprotein assay and percutaneous ultrasonography. Four patients were treated with surgical resection and one received transarterial oily chemoembolization (TOCE) as their primary treatments. There was one peri-operative death and the remaining three surgically treated patients were alive 4, 62, and 64 months after the resection. One patient developed recurrence 18 months after curative resection and was treated with TOCE. The patient with unresectable disease was alive for 50 months after the initial diagnosis. The surgical resection and overall survival rates of these patients were better than the published results. CONCLUSION: Early detection with regular serum alpha-fetoprotein assay and ultrasonographic study, vigilant care in the peri-operative period, long-term follow-up for detection and treatment of recurrence, as well as close collaboration between renal physicians and liver surgeons may improve the outcome of treatment of HCC in renal transplant recipients.

A long-term study on hyperlipidemia in stable renal transplant recipients.

OBJECTIVES: Hyperlipidemia is a common and important risk factor after renal transplantation, but there is little long-term data on its incidence, pattern, and evolution in stable renal allograft recipients on low dose maintenance immunosuppression. PATIENTS AND METHODS: A retrospective study was conducted on all patients who received kidney transplants from April 1, 1990 to March 31, 2000 at a single center, on their serial lipid profile during the first 3 yr after kidney transplantation. RESULTS: A total of 221 (122 male, 99 female; mean age 37.8 +/- 10.0 yr at the time of transplantation) Chinese adult renal allograft recipients were included. A 95.3% of patients were on cyclosporine and prednisolone based immunosuppression. Increases in total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) were noted, while the level of triglyceride (TG) decreased after renal transplant. The incidence of hypercholesterolemia (defined as TC >/= 6.3 mmol/L or LDL >/= 4.2 mmol/L) within the first year was 28.2 and 20.3%, respectively. The incidence rate decreased significantly in the second (5.4%, p = 0.000 and 6.4%, p = 0.003) and third year (9.5%, p = 0.003 and 4.9%, p = 0.021), but the incidence of patients having a high risk-ratio (defined as TC/HDL >/= 5) remained unchanged (6.9, 4.9 and 10.3% within the first, second, and third year, respectively). Treatment with statin was necessitated in 6.8, 13.6 and 21.7% of the patients at 1, 2, and 3 yr after transplantation, respectively. The prevalence rates of elevated TC and LDL were 18.3 and 18.9% at baseline, 40.6 and 33.3% after 1 yr, 32.8 and 27.3% after 2 yr, and 24.8 and 19.0% after 3 yr, despite treatment. The prevalence of patients with a high risk-ratio was 45.0% at baseline, 30.5% after 1 yr (p = 0.002), 22.6% after 2 yr (p = 0.000) and 21.8% after 3 yr (p = 0.000). Hypercholesterolemia at the time of transplantation was an independent predictor for post-transplant hypercholesterolemia (odds ratio 3.76, 95% confidence interval 1.47-9.62, p = 0.006). CONCLUSION: Renal transplantation is associated with a characteristic pattern of dyslipidemia, with increased TC, LDL and HDL, and a decrease in TG. Patients with pre-existing hypercholesterolemia were at higher risk for post-transplant hypercholesterolemia. Although the incidence of hypercholesterolemia peaks within the first year after transplantation, this remains a long-term complication in a significant proportion of patients on low dose immunosuppressive medications.

Incidence and outcome of antiglomerular basement membrane disease in Chinese.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti-GBM disease in Asians. To study the incidence and clinical characteristics of anti-GBM disease among Chinese patients, we reviewed our experience of anti-GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. METHODS: All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti-GBM antibodies were detected by either enzyme-linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti-GBM disease during this 11-year period, yielding an incidence of approximately 0.6 cases per million population per year. RESULTS: In this cohort, anti-GBM disease predominantly affected older patients (mean age: 58.6 +/- 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1-year renal and patient survival was 15% (95% CI 0-40%) and 70% (95% CI 42-98%), respectively. Most patients presented with non-specific symptoms as well as impaired renal function. Detection of anti-GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long-term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. CONCLUSION: Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long-term preservation of renal function after the initial attack is unusual.

Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses.

INTRODUCTION: Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome in children and young adults. We investigated its clinical presentations, steroid responsiveness, subsequent clinical course and patterns of relapse in older adults in whom it was diagnosed after the age of 50 years. METHODS: The clinical records of renal patients followed-up in a single out patient clinic were retrieved and those patients with biopsy-proven MCNS were included. Patients in the 18-50-year age range (Group A) at the time of biopsy were compared with those older than 50 years (Group B) with regard to baseline demographic data, clinical features and outcome of treatment. RESULTS: In all, 50 patients were studied, 35 in Group A (age at diagnosis: 38.8+/-11.91 years) and 15 in Group B (age at diagnosis: 70+/-6.85 years), with an overall follow-up duration of 72.08+/-63.42 months. Group B had a higher prevalence of hypertension and lower creatinine clearance at presentation, but the values of creatinine clearance for both groups were comparable with age-matched controls. One patient from Group B and two from Group A had spontaneous remission. Complete remission was achieved in 9.09, 45.45, 90.91 and 100% of Group B patients and 15.63, 62.5, 87.5 and 93.75% of Group A patients after 2, 4, 8 and 16 weeks of steroid therapy, respectively. The median time to complete remission and the duration of steroid treatment were similar for both groups. From Group B five patients and 22 patients from Group A relapsed during follow-up (P=0.055), with similar proportions of each group being early relapsers or frequent relapsers. The average number of relapses was 2.06 episodes for Group A, compared with 0.87 episodes for group B (P=0.062). Second agents were used in 20 Group A and four Group B patients (P=0.048). Complications of treatment were more common in Group A. None of the patients developed doubling of serum creatinine during follow-up. CONCLUSIONS: Clinical presentations of older patients with MCNS were similar to younger patients apart from the age-related decline of renal function and higher prevalence of hypertension. Both groups have similar steroid responsiveness, but older patients tend to have fewer relapses and require fewer second agents for treatment of relapses.

A 3-year, prospective, randomized, controlled study on amino acid dialysate in patients on CAPD.

BACKGROUND: Malnutrition is prevalent in patients on continuous ambulatory peritoneal dialysis (CAPD) and confers a poor prognosis. Inadequate nutrient intake is an important contributing factor. Although short-term studies have shown mild to modest nutritional benefit with amino acid dialysate, its long-term effects and tolerability remain obscure. METHODS: The authors have performed a 3-year, randomized, prospective, controlled study of amino acid dialysate in malnourished Chinese patients on CAPD. Sixty patients were assigned randomly to either replace 1 exchange daily with amino acid dialysate (Nutrineal; DAA group, n = 30) or to continue with dextrose dialysate (Dianeal; DD group, n = 30). RESULTS: The 2 groups had similar mortality, hospitalization duration, serial C-reactive protein levels, and drop-out rates during the study. Biochemical nutritional parameters including albumin and cholesterol decreased in the DD group but remained stable or increased in the DAA group. The composite nutritional index did not differ between the 2 groups throughout the study period. Triglyceride decreased only in DAA-treated patients. Normalized protein equivalent of nitrogen appearance and dietary protein intake showed a sustained increase only in DAA patients. The nutritional benefit of DAA appeared more prominent in women, whose lean body mass and body mass index was maintained with DAA but not with DD. Mass transfer area coefficient for creatinine increased in DAA-treated patients, whereas that for urea as well as macromolecular restriction coefficients remained stable. Total Kt/V(urea) and daily ultrafiltration volume were similarly maintained in the 2 groups throughout the study. CONCLUSION: Long-term administration of amino acid dialysate is well tolerated and presents a means to improve the nutritional status in high-risk patients. The current study, however, has not shown a significant effect of amino acid dialysate on patient survival.

Video-assisted thoracoscopic talc pleurodesis is effective for maintenance of peritoneal dialysis in acute hydrothorax complicating peritoneal dialysis.

BACKGROUND: Acute, massive, unilateral hydrothorax is an uncommon but well-recognized complication of peritoneal dialysis. Its clinical course and treatment outcome after a recently advocated technique of video-assisted thoracoscopic (VATS) talc pleurodesis remains unclear. METHODS AND RESULTS: Between July 1998 and March 2002, among 475 CAPD patients in two regional hospitals in Hong Kong, nine patients (three men, six women, mean age 53+/-12 years) developed acute hydrothorax due to pleuroperitoneal communication (R=8, L=1) within 5.8+/-4.2 months (median, 5.2 m; range, 2 days to 11.6 months) of commencing peritoneal dialysis. Analysis of simultaneously obtained peritoneal and pleural fluid in all subjects only showed concordance in protein content (consistently<4 g/l), while fluid glucose and lactate dehydrogenase levels were not comparable. The methylene blue test was negative (n=4). Radionuclide scan (n=6) and contrast CT peritoneography (CTP, n=3) detected pleuroperitoneal communication in half and one-third of the patients, respectively. All patients underwent pleurodesis achieved by talc insufflation into the pleural cavity under VATS guidance. All patients were successfully returned to peritoneal dialysis. After a mean follow-up of 18.8+/-12.5 months, hydrothorax recurred in one patient (at 7 months after pleurodesis), who was successfully treated by repeating the procedure. CONCLUSIONS: Hydrothorax complicating CAPD is more commonly right-sided, and tends to occur within the first year of starting peritoneal dialysis. Isotope scan and CTP are insensitive in diagnosing pleuroperitoneal communication. A low pleural fluid protein content is the most consistent biochemical finding. VATS talc pleurodesis is a safe and reliable treatment of choice that allows sustained continuation of CAPD with low recurrence rate.

A prospective randomized study on three different peritoneal dialysis catheters.

OBJECTIVE: We compared outcomes for catheters with different configurations: conventional straight, swan-neck straight tip, and swan-neck curled tip. DESIGN: The study was conducted as a prospective randomized controlled trial in the continuous ambulatory peritoneal dialysis (CAPD) unit of a university center. PATIENTS AND METHODS: We randomized 93 new regular CAPD patients without prior peritoneal dialysis (PD) catheter insertion to receive a conventional straight, double-cuffed catheter (CS), a swan-neck straight catheter (SNC), or a swan-neck curled tip catheter (SNC) in 2:1:1 ratio. RESULTS: The exit-site infection (ESI) rate was slightly lower with swan-neck catheters as compared with straight catheters, but the difference was not statistically significant. The peritonitis rate and overall catheter survival were similar. In Staphylococcus aureus nasal non carriers as compared with carriers, ESI-free catheter survival was significantly better with swan-neck catheters (p = 0.0302 and p = 0.82 respectively). As compared with SC catheters, SNC catheters had a significantly higher migration rate (p = 0.022). CONCLUSIONS: Swan-neck catheters were associated with a slightly better ESI rate, but SNC catheters are not routinely recommended because of a high migration rate. The SNS catheter is therefore recommended as the first-line catheter of choice, particularly in populations with a low rate of S. aureus nasal carriage.

Clinical features and genetic analysis of a Chinese kindred with Fabry's disease.

BACKGROUND: Fabry's disease is an X-linked recessive inborn error of glycosphingolipid catabolism resulting from deficient activity of lysosomal enzyme alpha-galactosidase A causing occlusive microvascular diseases affecting the kidney, heart, peripheral nerves and brain. It is an uncommon disease in the Oriental population. METHODS AND RESULTS: We report a Chinese kindred of Fabry's disease and the relevant clinical features are discussed. The diagnosis of Fabry's disease was based on serum alpha-galactosidase A activity and typical histological features from renal biopsy in the index patient. Genetic analysis of two hemizygous male patients revealed a missense mutation predicting a leucine to proline substitution (L14P) in the alpha-galactosidase gene causing classical Fabry's disease in this family. This is a novel point mutation not described previously in the literature and the second report describing novel genetic mutations for Fabry's disease in Chinese patients. CONCLUSIONS: Fabry's disease is rare in Chinese patients but this diagnosis should be considered in patients with positive family history of kidney disease and relevant clinical features.

Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients.

Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD 14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15+/-8.93 vs 35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD 14+/IL-10+ positive cells in the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25, P<0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-10 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.