Severe parvovirus B19 encephalitis after renal transplantation.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Treatment of FSGS with plasma exchange and immunadsorption.

In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be achieved with treatment. Currently, most children with FSGS are treated with cyclosporine and steroids after establishing steroid resistance, and approximately 60% of patients benefit from this therapy. For the remaining 40%, no generally approved therapeutic recommendations exist for children. We treated nine children with cyclosporine-resistant primary FSGS with plasma exchange (PE), two with relapsing FSGS after renal transplantation and seven with FSGS in their native kidneys. Three patients did not respond to PE, but five came into complete remission and one patient achieved partial remission. Three patients relapsed between 6 weeks and 2 years following cessation of PE, and were subsequently treated with plasma immunadsorption (PIA), which also reliably reduced proteinuria. The patients without response to PE tended to have a longer duration of the disease. We conclude that PE and PIA are a useful option for treatment of steroid- and cyclosporine-resistant FSGS, particularly if applied early in the course of the disease. Although more demanding on supportive resources, PIA seems preferable to PE, since there is no necessity for additional albumin or fresh-frozen plasma, as with PE.

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity.

Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal transplant recipients (10.8 +/- 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 +/- 2.7 (range 2.3-11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 +/- 96 micromol/l, lower than at the time of conversion (188 +/- 100 micromol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 +/- 69 micromol/l (P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 +/- 39 mg/ m2 per day to 59 +/- 13 mg/m2 per day in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1-18 months). After a median period of 21 days, a pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117 +/- 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 +/- 2.0 microg/ml, range 1.4-7.9 microg/ml. Mean 12 h MPA AUC was 70.6 +/- 28.1 (range 31.9-127) microg x h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2 per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.

Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression.

The recommended dosage for mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) for pediatric kidney transplant recipients is 600 mg/m(2) twice daily (b.i.d.). We recently published pharmacokinetic (PK) profiles of MMF in combination with tacrolimus (FK506): in order to keep the mycophenolic acid (MPA) pre-dose trough concentration between 2 and 5 microg/ml and to avoid side effects, mean MMF doses were reduced to 300 mg/m(2) b.i.d. In order to investigate whether this striking difference was due to alterations of MPA clearance by CyA or FK506, we analyzed PK profiles from 13 patients who received MMF without CyA or FK506, and compared these data with 14 patients who received a combination of MMF and FK506 and 15 patients who received MMF and CyA. Mean area under the curve (AUC) in all PK profiles was 61.9+/-23.8 microgxh/ml. Although the AUCs did not differ between the groups, the dose per square meter was significantly lower in patients receiving concomitant FK506 compared with CyA, and the dose-normalized AUC was significantly higher. The MMF doses were 1,158+/-301 mg/m(2) per day in the CyA group, 555+/-289 mg/m(2) per day in the tacrolimus group, and 866+/-401 mg/m(2) per day in the group without concomitant calcineurin inhibitor treatment. The apparent clearance of MPA is reduced in combination with tacrolimus. The reason for this remains unknown. There was a trend towards lower dose-normalized AUCs in the CyA group compared with the group without calcineurin inhibitor treatment. We conclude that concomitant medication alters the clearance of MPA. It is noteworthy that there was substantial interindividual variation, despite the rather marked differences between the groups, and therefore we recommend starting MMF in combination with CyA at a dose of 600 mg/m(2) b.i.d., in combination with tacrolimus at a dose of 300 mg/m(2) b.i.d., and without a calcineurin inhibitor at a dose of 500 mg/m(2) b.i.d., and adjusting doses using therapeutic drug monitoring of MPA.

Residual peritoneal volume and body size in children on peritoneal dialysis. [Members of the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS)].

Residual peritoneal volume may play an important role in dialysis efficacy and abdominal compliance in patients on chronic peritoneal dialysis (CPD). In children on CPD, the relationship between residual peritoneal volume and different measures of body size, as well as the day-to-day variability of residual volume, have not been established. We therefore investigated, on two consecutive days, residual peritoneal volume in 25 children on CPD, using the dextran dilution technique. Residual volume was linearly correlated with body size. Residual volume was independent of body size when normalized to body surface area, but decreased with increasing body size when normalized to body weight (r = -0.62, p < 0.001). Mean residual volume was 79 +/- 25 mL/m2, with an intra-individual day-to-day coefficient of variation of 21% +/- 15%. Residual volume was not correlated with the duration of PD, frequency of peritonitis, or peritoneal permeability as estimated by D/P creatinine or D/D0 glucose. In conclusion, residual peritoneal volume is constant across the pediatric age range when normalized to body surface area. It accounts for approximately 8% of the usual fill volume in patients on CPD. Residual volume is not a major confounder of the transport status estimation obtained by peritoneal equilibration test.

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study.

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.