Early sirolimus therapy in renal transplant recipients at high risk: is it justified?

BACKGROUND: We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction. PATIENTS AND METHODS: In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)-mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded. RESULTS: Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome. CONCLUSION: Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.

Low levels of Th1-type cytokines and increased levels of Th2-type cytokines in kidney transplant recipients with active cytomegalovirus infection.

BACKGROUND: Cytomegalovirus (CMV) infection is a major complication after kidney transplantation. It is clear that Th1 and Th2 cell subsets are of major importance in determining the class of immunoprotective function in infectious diseases. Given the strong influence exerted by Th1- and Th2-type immunity on the outcome of infections, we felt it important to elucidate the levels of Th1- and Th2-type cytokines to CMV-related antigens in kidney recipients and to identify antigens that play an essential role in preventing the development of CMV infection and/or disease. METHODS: One hundred twenty subjects were followed for CMV infection by the antigenemia assay. We investigated peripheral blood mononuclear cells (PBMCs) responses to five CMV-related peptide antigens (pp65, gB, pp150, pp28, and pp38). Stimulation index was determined by radioactive thymidine uptake, while the production of Th1-type cytokines (interferon-gamma and tumor necrosis factor-alpha) and Th2-type cytokines (interleukins-4 and -10) were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of Th1-type cytokine production after stimulating PBMCs with CMV-related antigens gB and pp150 resulted in significant decreases in the levels of interferon-gamma, while pp65, pp150, and pp38 produced significant decreases in the level of tumor necrosis factor-alpha between the two groups (P < .05). For Th2-type cytokines only pp28 produced a significant increase in the level of interleukin-10 between the two groups (P < .05). Regarding the Th1:Th2 ratios, a lower Th1-bias was observed among the CMV-positive patients for PBMCs stimulated with three CMV-related antigens (pp65, pp38, and pp28). CONCLUSION: Low levels of Th1-type cytokines and increased levels of Th2-type cytokines upon stimulation with CMV-related peptide antigens were associated with reduced cell-mediated immunity to CMV, thus seeming to correlate with active CMV infections.

Long-term follow-up of 100 high-risk renal transplant recipients converted from calcineurin inhibitors to sirolimus: a single center experience.

While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean +/- SD age was 38.5 +/- 15.6 years, including pediatric and geriatric age groups. Mean +/- SD body mass index (BMI) was 28.99 +/- 8.0 and 40% had a BMI > 30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean +/- SD time to start of SRL was 11.9 +/- 22.8 months posttransplantation. Proteinuria > 2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P = .001, P = .0003, and P = .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P < .0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.

Association of low heart rate variability with atherosclerotic cardiovascular disease in hemodialysis patients.

OBJECTIVE: The aim of this study was to investigate the left-ventricular (LV) mass-adjusted association between low heart rate variability (HRV) and atherosclerotic cardiovascular disease (ASCVD) among hemodialysis patients in Kuwait. SUBJECTS AND METHODS: One hundred and eight patients were enrolled in the study. HRV time domain measures were obtained by 48-hour Holter monitoring, including the standard deviation of all R-wave-to-R-wave (RR) intervals (SDNN), standard deviation of all 5-min averaged intervals (SDANN), HRV triangular index (HRV-TI), percent of adjacent RR intervals differing by >50 ms (pNN50), and root mean square of sums of squares of all differences (rMSSD). Left ventricular ejection fraction (LVEF) and LV mass index (LVMI) were measured by M-mode echocardiography. Comorbidity was assessed using medical record review. Prevalent ASCVD was defined as coronary artery, cerebrovascular, or peripheral vascular disease. RESULTS: Prevalence of ASCVD, LV hypertrophy, and LVEF <40% were 56, 59, and 10%, respectively. The SDANN was negatively associated with ASCVD (-20 ms; p = 0.003), LV systolic dysfunction (-20 ms; p = 0.001), elevated LVMI (-20 ms; p = 0.002), hypertension (-34 ms; p = 0.01), and diabetes (-20 ms; p = 0.001). After adjustment for hypertension and LVMI using logistic regression, ASCVD was associated with the lowest quartile of SDANN (OR = 4.3, p = 0.009), HRV-TI (OR = 3.3, p = 0.03), and SDNN (OR = 2.3, p = 0.10). These associations persisted after adjusting for LVEF. CONCLUSION: In dialysis patients, low HRV indices were strongly associated with prevalent ASCVD, independent of LVMI and LVEF. The interrelationships among HRV, diabetes, hypertension, and LVMI should be addressed in studies of HRV and ASCVD.

Hypertension and hyperparathyroidism are associated with left ventricular hypertrophy in patients on hemodialysis.

Conflicting data for association between left ventricular hypertrophy (LVH) and secondary hyperparathyroidism has been reported previously among dialysis patients. The present study was conducted to evaluate the association of hyperparathyroidism and hypertension with LVH. Charts of 130 patients on hemodialysis for at least six months were reviewed. All were subjected to M-mode echocardiography. Left ventricular mass (LVM) was calculated by Devereux's formula. LVM Index (LVMI) was calculated by dividing LVM by body surface area. Sera were analyzed for intact parathyroid hormone (iPTH). iPTH of > 32 pmol/l and a mean blood pressure (MAP) of > 107 mmHg were considered high. Patients were stratified into groups according to their MAP and iPTH. A total of (47.7%) patients were males and 68 (52.3%) were females. Their median age was 57 years. The median duration on dialysis was 26 months. Forty eight (36.9%) patients had high BP and 54 (41.5%) had high iPTH. Both high BP and high iPTH were present in 38 (29.2%) patients. Analysis of the relationship between LVM, LVMI, MAP and iPTH showed that LVM and LVMI were significantly (P < 0.001) higher in patients with concomitant high BP and high iPTH. LVMI was significantly higher in patients with high iPTH alone. Concomitant high iPTH and high MAP increase the risk of LVH in hemodialysis patients. High iPTH alone might contribute in escalating LVH. Adequate control of hypertension and hyperparathyroidism might reduce the risk of developing LVH.

Is combined pretransplantation seropositivity of kidney transplant recipients for cytomegalovirus antigens (pp150 and pp28) a predictor for protection against infection?

OBJECTIVE: This study was aimed at detecting antibodies to the antigens which may contribute to protection against cytomegalovirus (CMV) infection after organ transplantation. MATERIALS AND METHODS: A total of 203 kidney transplant patients were enrolled in the study. Based on CMV antigenemia assay, 23 patients were antigen-positive and of the remaining 180 antigen-negative patients, 46 were selected as controls matched for age, gender and source of kidney. The 69 kidney recipients (KR) had CMV antibody due to previous infection and were followed up for a period of 6 months after transplantation for the development of active CMV infections by the antigenemia assay. Antibody responses to five CMV-related peptide antigens (pp65, gB, pp150, pp28 and pp38) were investigated by enzyme immunoassay and their presence was correlated with the results of the CMV antigenemia assay. RESULTS: Of the five CMV-related peptide antigens, only gB antigen showed response to the antibody in 10/23 (43.5%) antigen-positive patients and 9/46 antigen-negative patients and the difference was statistically significant (p = 0.048). On the other hand, there was no significant difference in antibody responses between the antigen-positive and antigen-negative KR to the other four CMV peptide antigens (p > 0.05). However, among the antigen-positive KR there was only 1 patient who had antibodies to both pp150 and pp28 antigen, while among the antigen-negative KR, 22 of 46 (47.8%) had the antibodies (p < 0.001). CONCLUSION: The findings suggest that the combined presence of antibodies against the pp150 and pp28 antigens may indicate a lower risk of CMV reactivation after kidney transplantation.

Oral valgancyclovir versus intravenous gancyclovir for cytomegalovirus prophylaxis in kidney transplant recipients.

BACKGROUND: Prophylaxis against cytomegalovirus (CMV) is a regular practice in organ transplantation. Oral valgancyclovir appears to be an interesting alternative to the usual intravenous form. PATIENTS AND METHODS: We prospectively compared the response of intravenous gancyclovir for 2 weeks (GAN; n=41) to oral valgancyclovir for 2 weeks (VAL2w; n=23) or 3 months (VAL3m; n=46) in kidney transplant recipients receiving induction immunosuppression. CMV antigenemia assay and/or polymerase chain reaction (PCR) were used for viral detection. Patients were followed for a minimum of 6 months posttransplantation. SPSS software was used for statistical analysis using a cutoff of significance as P<.05. RESULTS: There was no statistical difference in the demographic features among the study groups. However, human leukocyte antigen (HLA) match was better in the VAL3m group and the patients of this group received less ATG induction immunosuppression (41.3%) compared with the GAN group (100%). The incidence of acute rejection was not different among the study groups. There was a higher incidence of fever with positive CMV tests in the VAL2w group (P=.035) compared with the other groups, while leukopenia with a negative CMV test was significantly higher in the VAL3m group (P=.04). The incidence of CMV disease was higher in the VAL2w group (30.4%) compared with the GAN group (14.6%) or the VAL3m group (8.7%). Renal function was significantly worse in the VAL2w group at 3 and 6 months (P=.011 and .02, respectively). CONCLUSIONS: Three months oral valgancyclovir prophylaxis for CMV was a more effective regimen compared with intravenous gancyclovir for 2 weeks. Shorter courses were associated with a higher incidence of CMV infection and poorer graft function. Leukopenia observed in patients receiving valgancyclovir may be a drug-related side effect.

Hyperinfection strongyloidiasis: an anticipated outbreak in kidney transplant recipients in Kuwait.

BACKGROUND: Hyperinfection strongyloidiasis is a potentially fatal syndrome associated with conditions of depressed host cellular immunity. A high degree of suspicion is required to detect cases early and thereby avoid a fatal outcome. PATIENTS AND METHODS: Three consecutive cadaveric kidney transplant recipients died within 2 months from hyperinfections with strongyloides. All members of the transplant team were involved in a campaign to localize the source of infection, identify and treat affected patients, and provide adequate prophylaxis to other transplant recipients. We reviewed cadaveric donor files and screened 61 hospital personnel, 27 hospital inpatients, and the 87 hospital outpatients transplanted in a year's time before that event for a possible source. The screening test included analysis of fresh stool samples on 3 consecutive days for strongyloides larvae. The anti-helminthic drug albendazol was administered to all patients during screening. They were followed for possible development of the disease during the infectivity period. RESULTS: The first 2 recipients received their kidneys from 1 cadaveric donor, while the third received it from a different donor. Both donors came from areas endemic for strongyloidiasis. The 3 recipients were on tacrolimus-based immunosuppression. The twin recipient of the second kidney was on cyclosporine and did not manifest a disease. All stool samples taken for screening were negative for the infective larvae. None of the other recipients developed the disease. CONCLUSIONS: Cadaveric donors were the possible source for this outbreak. Cyclosporine probably has a protective effect against strongyloides. In our setting, screening of cadaveric donors for strongyloides is mandatory before accepting them for donation, and oral prophylaxis is required for all recipients.

De novo Crohn's disease in a renal transplant recipient.

The prevalence of inflammatory bowel disease (IBD) after renal transplantation is affected by the immune tolerance and the modality of immunosuppression. Mycophenolate mofetil (MMF) may have a promoting effect on the development of posttransplantation erosive enterocolitis and a Crohn's disease-like pattern of colitis. We have presented a 40-year-old man with end-stage renal disease due to chronic glomerulonephritis who commenced hemodialysis for 2 months before receipt of a live unrelated renal transplant. He developed early posttransplantation diabetes mellitus and an anti graft rejection episode, which responded to a methylprednisolone pulse and OKT3 treatment. His immunosuppressive regimen included prednisolone, MMF, and tacrolimus. Three years after transplantation, he developed mild constitutional symptoms, mouth ulcerations, and chronic intermittent bloody diarrhea. Colonoscopy showed active segmental colitis with aphthous ulcers, involving the proximal descending colon and the splenic flexure. Colonic biopsies showed distended and branched crypts in the ascending colon, moderate active chronic colitis with regenerative atypia, skipping appearance, and ulceration in the splenic flexure and descending colon. The edematous crypts were associated with ulcerations in the sigmoid colon and rectum. The features were highly suggestive of Crohn's disease. He was successfully treated with high-dose steroids and 5-aminosalicylic acid. Subsequently, he developed chronic transplant glomerulopathy and restarted hemodialysis. We concluded that de novo Crohn's disease may develop in renal transplant recipients despite immunosuppressive therapy especially with MMF immunosuppression.

Renal artery stenosis in patients with peripheral vascular disease in Kuwait.

OBJECTIVE: The aim of this study was to identify the incidence of atherosclerotic renal artery stenosis (RAS) in patients with peripheral vascular disease (PVD) and its relation to any known risk factors. SUBJECTS AND METHODS: This prospective study was conducted on 212 patients who were subjected to peripheral angiography for symptoms of PVD over a 3-year period from 1995 to 1998 at the Mubarak Al-Kabeer Hospital, Kuwait. Angiographic evidence of atherosclerotic disease and its severity was recorded in renal, abdominal aorta, iliac, femoral, popliteal and below-knee arteries. In addition, a detailed search of identifiable risk factors was done using history, clinical examination and laboratory studies. RESULTS: The incidence of significant atherosclerotic RAS (more than 50% diameter stenosis) in patients with PVD was 15/212 (7.07%) with no significant difference in ratio between males and females (p = 0.3) compared to that of PVD alone. Patients with common iliac and femoral artery lesions had a high incidence of RAS (93.3 and 86.7%, respectively) with more than 80% probability in RAS patients with involvement of these vessels. There was significant renal impairment (p < 0.005), as assessed by serum creatinine levels, in patients with RAS compared to those who did not have it. There was a high incidence of smoking in patients with RAS (p = 0.02), and smoking was the only risk factor identified in these subjects. CONCLUSIONS: Patients with iliac or femoral atherosclerotic disease have a high probability of associated RAS. Presence of renal impairment in patients with PVD is highly indicative of RAS. Smoking is the only identified risk factor for RAS in association with PVD in our population.

Results in 158 consecutive cadaveric renal transplantations.

OBJECTIVES: We investigated the outcome of deceased donor kidney transplantations performed in a single center in a developing country. MATERIALS AND METHODS: A total of 158 patients (69 male and 89 female patients, including 32 children) received kidney grafts obtained from deceased donors between March 1996 and October 2004. Cadaveric renal grafts were transplanted after a cold ischemia time of 4 to 24 hours (mean, 12.5 hours). Retransplantation was performed in 19 recipients. Induction immunosuppression was achieved with antithymocyte globulin. The diagnosis of acute graft rejection was based on histopathological findings. RESULTS: Primary graft function was observed in 77% of cases. Posttransplantation complications were: surgical (n = 60; 38%), systemic bacterial and viral infections (n = 33; 21%), acute rejection (n = 47; 30%), and malignancy (n = 2; 1.3%). Seventeen recipients died with a functioning graft, and 23 more grafts were lost. The 7-year actuarial survival rates were 89% and 75% for recipients and grafts, respectively. CONCLUSIONS: The kidney transplantation program in Kuwait is steadily growing. Kidney grafts obtained from deceased donors contributed 28% of the transplantation activity and were associated with a high rate of primary function. Overall actuarial recipient and graft survival rates were comparable to those reported by larger centers.

The area under the concentration-time curve versus trough and peak blood level monitoring in renal transplant recipients on cyclosporine.

OBJECTIVE: The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. METHODS: Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. RESULTS: There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was <70% for cyclosporine trough levels (P < .02) and >90% for peak cyclosporine blood levels (P < .001) when related to the calculated area under the curve. The calculated area under the curve was approximately 6000 ng/mL/h following transplantation, gradually decreasing to approximately 3000 ng/mL/h at 1 year. Both appeared to the acceptable therapeutic values. CONCLUSION: Calculating the area under the curve using trough and peak blood levels versus using isolated readings for either of these levels alone is the most effective method of monitoring cyclosporine in recipients undergoing renal transplant.

Single daily dose administration of cyclosporine in renal transplant recipients: a preliminary report.

INTRODUCTION: Cyclosporine microemulsion has been the mainstay immunosuppressive agent in renal transplantation for years. Since single daily dosing of cyclosporine is rarely used, the objective of this investigation was to evaluate the efficacy of a single daily dose versus twice daily dosing of cyclosporine in renal transplant recipients. METHODS: Retrospective evaluation of single-dose cyclosporine use was conducted for 15 renal transplant recipients for 12 months (study group). Equal numbers of matched renal transplant recipients were selected for age, sex, human leukocyte antigen mismatch, donor type, and immunosuppressive regimen (control group). Cyclosporine trough level and peak cyclosporine blood levels, 12-hour cyclosporine profile, and the area under the concentration-time curve were measured. RESULTS: There was a significant difference in cyclosporine peak blood level and calculated area under the curve after shifting to single-dose cyclosporine (P = .001). In the study group, the mean area under the curve was significantly below the average therapeutic range before (3154 ng/mL/ho) versus 5532 ng/mL/h after shifting to the single-dose regimen (which was therapeutic). This value was 5749 ng/mL/h in the control group. Total daily cyclosporine dose was lower in the study group when compared with the control group at 6 and 12 months (P = .01). There were significantly fewer adverse effects in patients in the study group than in patients in the control group. CONCLUSION: We conclude that although cyclosporine dose should be individualized in renal transplant recipients, a single dose of cyclosporine has the added advantage of decreasing dosages and cyclosporine-related adverse effects while maintaining optimal graft function.

Early acute rejection episodes in renal transplantation in relation to immunosuppression protocols: an audit of 100 cases.

INTRODUCTION: Early acute rejection episodes (ARE) have deleterious effects on graft outcomes. The incidence of ARE in the first 3 months has been reported to be <20%. In a recent audit of ARE among 100 renal transplants, we observed the rates to be high (30%). We retrospectively collected details of donor type, induction therapy, immunosuppression medications, drug levels, HLA mismatches, acute tubular necrosis (ATN), and delayed graft function (DGF) to correlate with ARE and response to therapy. RESULTS: Thirty rejection episodes occurred after a mean period of 14.3 days after transplantation. Ninety-one patients had induction treatment with either antithymocyte globulin (ATG) or interleukin 2 receptor antibodies (IL2 Rab). The drugs included cyclosporine, mycophenolate, sirolimus, azathioprine, and prednisolone in these patients. There was no significant difference in ARE among the different drug protocols (30.7%-35.2%). Subjects with 4 or more HLA mismatches displayed more ARE (40.3%) compared with those with 3 or less (23%). Subjects with ATN or DGF immediately posttransplantation had a higher incidence of ARE (39.2%) than those without them (26.3%). Deceased donor recipients had a higher episode of ARE (45.1%) compared with live related donor recipients (25%). On stratifying the known risk factors for ARE, subjects with no risk factors had the least (22.2%) ARE compared with those with one (32.5%) or two (47.6%) risk factors. Subjects who failed to achieve adequate cyclosporine (C2) levels showed significantly higher rates of ARE (86.9%) than those with adequate or higher levels (8.6%). CONCLUSION: Higher HLA mismatches, DGF, deceased donor, and failure to achieve adequate cyclosporine levels were observed to be major risk factors for the development of ARE.

Safety of caspofungin for treating invasive nasal sinus aspergillosis in a kidney transplant recipient.

INTRODUCTION: Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. CASE SUMMARY: This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient's renal and hepatic function returned to normal. CONCLUSION: This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.

BK virus nephropathy in renal transplant recipients in Kuwait: a preliminary report.

INTRODUCTION: BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. PATIENTS AND METHODS: We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. RESULTS: No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 +/- 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 +/- 58 (87 to 285) micromol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 +/- 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) micromol/L, which is better than the renal function at diagnosis. CONCLUSION: The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Vascular calcification in dialysis patients.

UNLABELLED: The risk factors for vascular calcification (VC) in dialysis patients include duration of dialysis, diabetes mellitus, aging, hyperphosphatemia, hyperparathyroidism, and calcium or vitamin D supplementation. This study was performed to evaluate the prevalence of and risk factors for VC in our dialysis population. METHODS: One hundred twenty-nine chronic dialysis patients underwent plain x-rays of the hands for VC. Patients were grouped as either positive (PVC) or negative (NVC) for VC. Age, gender, duration of dialysis, presence of non-insulin-dependent diabetes mellitus (NIDDM), oral calcium, and 1alpha-hydroxyvitamin D3 supplement, serum levels of calcium (Ca), phosphorus (P), calcium phosphorus product (CaxP), alkaline phosphates (ALP) and intact parathyroid hormone (iPTH) were compared between the two groups. RESULTS: Thirty-four patients (26.35%) showed VC. There were no differences between PVC and NVC patients for duration of dialysis (38.4 +/- 27.7 for PVC and 34.6 +/- 31.2 months for NVC, P = .80), levels of serum Ca (P = .26), P (P = .19), CaxP (P = .33), ALP (P = .89), or iPTH (P = .24). Similarly, oral calcium and 1alpha-hydroxyvitamin D3 intake were not different between the two groups (P = .971 and P = .3710 respectively). Compared to NVC patients, PVC patients were older (56.3 +/- 10.4 versus 47.5 +/- 16.1 years, P = .008) and had a greater incidence of NIDDM (17/34 PVC and diabetic versus 20/95 NVC, P = .001). In conclusion, for patients with a medium length of dialysis, the duration of dialysis as well as the doses of calcium salts and of 1alpha-hydroxyvitamin D3 were not significantly associated with vascular calcifications, but it was not possible to exclude a role for these and other factors in patients with longer dialysis.

Baseline cardiac troponin I in patients on maintenance dialysis.

INTRODUCTION AND OBJECTIVES: There have been conflicting reports in the medical literature regarding baseline levels of cardiac troponins and their usefulness as specific markers of acute myocardial injury in patients on maintenance dialysis. Hence we undertook a study of the normal range of baseline cardiac troponin I (cTnI) in patients on maintenance dialysis in our center. METHODOLOGY: Seventy-five patients aged 45 years or more on maintenance dialysis for at least 1 month were included in the study. None had had an acute cardiac event requiring admission to the hospital during the preceding month. Samples of blood were collected and cTnI levels were estimated using an immunoenzymatic assay (Access Immunoassay system, Beckmann). Correlation of cTnI with gender, age, body mass index (BMI), and adequacy of dialysis (Kt/v) were also done. RESULTS: Forty-six (61.3%) patients were on maintenance hemodialysis and 29 (38.6%) were on peritoneal dialysis. Twenty-four (32%) were over the age of 65 years and 37 (49.3%) were men. Levels of cTnI ranged from 0.000 to 0.568 ng/mL, with mean of 0.040 +/- 0.080. Only six (8%) had levels above 0.1 ng/mL, which was the cut off level for significance in our laboratory. There was no statistically significant correlation of cTnI levels with gender, age, BMI, or Kt/v. CONCLUSIONS: Baseline cTnI levels were below significant levels in the majority of maintenance dialysis patients aged at least 45 years or more. Hence cTnI can be used as a valid marker of acute myocardial injury in this group of patients.

Profiled hemodialysis reduces intradialytic symptoms.

A prospective study on the effect of profiled hemodialysis on intradialytic symptoms was undertaken among patients recruited between September 2002 and December 2002. Evaluated intradialytic symptoms included hypotension, muscle cramps, dizziness, headache, nausea, discomfort, thirst, and shortness of breath. Symptomatic patients were allocated to one mode of combined sodium and ultrafiltration profile during hemodialysis. The programs were readily available on Fresenius MC 4008 H&E hemodialysis machines. Evaluation was performed before profiling and at 2, 4, and 6 weeks into the profiled hemodialysis. On standard hemodialysis 40 (36.4%) patients were symptomatic. Hypotension was reported in 29 (72.5%) of patients receiving standard treatment. Dizziness, headache, and muscle cramps were reported in 22 (55%), 15 (37.5%), and 9 (22.5%) patients, respectively. These symptoms were significantly (P <.05) improved at 2, 4, and 6 weeks of profiling. Other symptoms, such as discomfort, nausea, vomiting, and thirst, were infrequently reported among patients without or with profiling. There was no significant difference between the applied profiles when compared with each other. In conclusion, sodium and ultrafiltration profiling are effective techniques to reduce acute adverse side effects of hemodialysis. They improve patient well-being and dialysis tolerance, minimize interventions during dialysis.