Intermediate dose cidofovir does not cause additive nephrotoxicity in BK virus allograft nephropathy.

BKVAN has emerged as a major morbidity in kidney transplant recipients. Among treatment options is cidofovir, which can be nephrotoxic. We previously reported that intermediate dose cidofovir could be used without significant nephrotoxicity. We present extended results of the same treatment protocol in a larger cohort and with longer follow up. Diagnosis of BKVAN was based on detection of BK viral DNA from plasma and renal allograft biopsy tissue. All patients received cidofovir (0.25-1 mg/kg/dose) every 2-3 wk. Total number of cidofovir doses ranged from 1 to 18 (mean 8). This report includes eight patients, aged 5-21 yr, treated with intermediate dose cidofovir. Median follow-up was 11 months (range 4-32). Mean fall in reciprocal of serum creatinine (1/sCr) from baseline at BKVAN diagnosis was 64% (range 28-120%). A time-series plot of plasma BK virus PCR and 1/sCr showed marked reduction in viral loads without significant deterioration in 1/sCr from the initial value at BKVAN diagnosis. In this larger series with extended follow up, intermediate dose cidofovir without probenecid for the treatment of BKVAN continues to show stabilization of renal function without progression to renal failure.

Hemodialysis catheter-related bacteremia in children: increasing antibiotic resistance and changing bacteriological profile.

BACKGROUND: Catheter-related infections limit catheter survival. The success of antimicrobial therapy for the treatment of patients with hemodialysis catheter-related bacteremia (HD-CRB) depends on the infectious organisms. We determined whether the rate of positive blood culture results per tunneled catheter-days, the spectrum of bacterial isolates, and their antibiotic susceptibility changed over time in our pediatric dialysis unit. METHODS: Data were collected retrospectively for all positive blood culture results from long-term hemodialysis patients in our pediatric unit from July 1990 to July 1995 (period A) and July 2000 to July 2005 (period B). RESULTS: Rates of HD-CRB were similar between periods A and B (2.1 versus 2.2/1,000 catheter-days). In period A, 33% of isolates were coagulase-positive staphylococci, with Staphylococcus aureus accounting for 72% of these. In period B, the most common organism was Staphylococcus epidermidis (28%), whereas coagulase-positive staphylococci were identified in only 17%. There was a larger number of gram-positive bacilli in period B (20%) compared with period A (4%). A significant decrease in susceptibility to penicillins (40% to 5%; P = 0.007) and cephalosporins (58% to 21%; P = 0.04), but not aminoglycosides, was noted for gram-positive bacteria. There was no significant change in susceptibility of gram-negative bacteria to cephalosporins and aminoglycosides in either period. CONCLUSION: Both types of organism and antibiotic sensitivity patterns have changed over time. Based on these data, we changed our empiric antibiotic combination for HD-CRB to vancomycin plus an aminoglycoside.

Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy.

We have previously reported sirolimus (SRL) pharmacokinetics (PK) in pediatric renal transplant recipients on a calcineurin inhibitor (CNI)-free protocol. We now report pediatric SRL PK in pediatric renal transplant patients receiving SRL + CNI. SRL was dosed to achieve target trough levels between 10 and 20 ng/mL. We performed 49 SRL PK profiles in pediatric renal transplant recipients receiving SRL in combination with either cyclosporine (CsA; 25 profiles), or tacrolimus (TCL; 24 profiles). Ten of the SRL + TCL profiles were obtained from children receiving SRL on a b.i.d. dosing regimen. All other SRL profiles were q.d. regimens. We calculated, the maximum concentration (C(max)), AUC, apparent clearance (aCL; dose/AUC) for dose in mg/m(2), and mean residence time (MRT). SRL levels were measured at 6 and 7 time points for b.i.d. and q.d. dosing, respectively. Regression analysis of SRL trough values vs. AUC showed good correlation in the SRL q.d. + CsA, SRL q.d. + TCL, and SRL b.i.d. + TCL groups (r(2) = 0.95, 0.68, and 0.44, respectively). SRL aCL corrected for body surface area was higher in children aged 0-5 yr receiving SRL with either CsA or TCL. SRL dosing schedule should be tailored to each patient. Higher SRL aCL may be present in younger children when administered with CNI.

Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy.

BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti-viral therapy with low-dose cidofovir (0.25-0.42 mg/kg/dose) has been used successfully in some patients, but dose-related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate-dose cidofovir (0.75-1.0 mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20 yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2 million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low-dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate-dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate-dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate-dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate-dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.

Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.

In adult patients with ESRD, calcific uremic arteriolopathy (CUA) is an uncommon but life-threatening complication. No effective therapy exists, although anecdotal case reports highlight the use of sodium thiosulfate (STS), a calcium-chelating agent with antioxidant properties. CUA is rare in children, and STS use has not been reported. The objective of this study was to determine the influence of STS treatment on three patients with CUA in a pediatric chronic dialysis unit. The patients were between 12 and 21 yr of age; two were male; and primary diagnoses were obstructive uropathy, renal dysplasia, and calcineurin nephrotoxicity. Time from ESRD to CUA diagnosis was 1, 9, and 20 yr. Diagnosis was made by tissue biopsy and three-phase bone scan. Pain was the presenting symptom. Initial treatment included discontinuation of calcitriol and use of non-calcium-based phosphate binders and low-calcium dialysate concentration. STS dosage was 25 g/1.73 m(2) per dose intravenously after each hemodialysis session. For optimization of removal of calcium deposits, patient three received a combination of STS and continuous venovenous hemofiltration for the first 10 d. All patients demonstrated rapid pain relief. Within weeks, skin induration and joint mobility of the extremities improved. Radiographic evidence of reduction in the calcium deposits occurred within 3 mo of initiation of STS. The only complication was prolonged QT interval in one patient as a result of hypocalcemia, who was resolved by use of a higher dialysate calcium concentration. STS seems well tolerated in children and young adults with CUA and has mild adverse effects. For determination of its efficacy, optimum dosage, duration of therapy, and dialysis modality, controlled trials are needed.

Hodgkin's lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient.

Lymphoid malignancies such as post-transplant lymphoproliferative disease (PTLD) are a major complication of solid organ transplantation. Hodgkin's lymphoma (HL) is not part of the typical spectrum of PTLD, but has rarely been reported as a separate complication. We report a case of HL occurring after previous PTLD in a renal transplant recipient. A 9-yr-old girl with end-stage autosomal recessive polycystic kidney disease received a cadaveric renal transplant at 1 yr of age. She developed polymorphic PTLD localized to the bone marrow at 6 yr post-transplant. She was treated with reduction of immunosuppression and alpha-interferon. No chemotherapy or anti-B cell antibody was administered. The PTLD resolved and kidney graft function remained stable. At 9 yr post-transplant, she presented again with fever of 2 wk duration, associated with enlarged lymph nodes at multiple sites. A lymph node biopsy revealed the presence of classic Reed Sternberg cells positive for CD15, CD30 and EB RNA. She was treated with standard combination chemotherapy for HL with COPP/ABV. All immunosuppressive agents were discontinued except for low dose prednisone. The patient had an excellent response, with resolution of her lymphadenopathy and maintenance of stable graft function. RS like cells have been reported in the setting of PTLD, but these cells possess an activated B cell phenotype, are EBV negative and CD15 negative. True HL following PTLD has been reported in only three previous cases, with good response to standard chemotherapy in each.

Nephrogenic fibrosing dermopathy in pediatric patients.

Nephrogenic fibrosing dermopathy (NFD) is a rare and recently recognized sclerosing skin disorder of unknown etiology. Reported cases have occurred in patients with chronic renal failure, with or without renal replacement therapy. All previous cases have been reported in older adult patients. We describe two pediatric patients who recently developed this condition and review the existing literature for NFD. Our patients included an 8-year-old boy on peritoneal dialysis with no prior renal transplant and a 19-year-old boy on hemodialysis with a history of previous failed renal transplants. We speculate that the recent emergence of this condition and occurrence in patients with chronic renal failure suggest an association with some newer pharmacological agent that has recently come into wide use. Since both our patients also had previously experienced large vessel thrombosis, hypercoagulable states may also be implicated.

Cat scratch disease and acute rejection after pediatric renal transplantation.

Cat scratch disease (CSD) can lead to unexplained fever, generalized lymphadenopathy and organomegaly in immunocompetent individuals. CSD has rarely been reported in immunocompromised transplant recipients, where its clinical features would mimic the more common post-transplant lymphoproliferative disease (PTLD). We report three cases of CSD seen recently in children who had received prior kidney transplants. The three children were between 7 and 9 yr old, and had received kidney transplants 2-4 yr prior, with stable renal function. In each case, there was unexplained fever with either lymphadenopathy or organomegaly. The diagnosis of CSD was suggested by a history of new cats being introduced into each household and confirmed in all cases by the serological presence of a significant titer (> 1 : 64) of IgM antibodies to Bartonella henselae. Tests for other bacterial infections, cytomegalovirus and Epstein-Barr virus infections were negative. All the patients showed a clinical improvement with anti-microbial therapy. In patients A and B, the CSD was associated with an acute rejection episode shortly after diagnosis. The rejection episodes were reversed by intravenous steroid pulse therapy. Only four cases of CSD have been previously reported following solid organ transplantation. Acute rejection following CSD has not been previously reported. CSD should be included in the differential diagnosis of fever in the post-transplant setting, especially where PTLD is suspected.

Extracorporeal removal of toxic valproic acid levels in children.

Toxic ingestion of valproic acid is difficult to treat as no antidote exists and hemodialysis has been considered ineffective for clearance due to high protein binding of this drug. Recent reports suggest that protein binding of valproic acid is saturated at toxic levels, thereby allowing for removal of free drug by extracorporeal circuits. We describe our experiences in two children with toxic blood levels of valproic acid, in whom we were able to achieve effective clearances by extracorporeal removal without charcoal hemoperfusion. In an 18-year-old girl with initial valproic acid levels of 663 microg/ml (therapeutic 46-88 microg/ml), the elimination constant (k(el)) increased five- to eightfold from 0.04/h pre dialysis and 0.06/h post dialysis to 0.31/h during high-flux hemodiafiltration. In the same time periods, drug half-life reduced from 15.96 h pre dialysis and 21 h post dialysis to 2.23 h during hemodiafiltration. In a younger 18-month-old child with initial levels of 922 microg/ml, k(el) was fivefold higher at 0.25/h during conventional hemodialysis, compared with 0.05/h after dialysis. Similarly, the drug half-life was 2.9 h during dialysis and 12.9 h after dialysis. Both conventional hemodialysis and high-flux hemodiafiltration are effective treatment modalities that should be offered to all pediatric patients with valproic acid ingestion and neurological compromise.

Associations with medication adherence among ethnically different pediatric patients with renal transplants.

This study examined perceived medication regimen characteristics as factors in levels of medication adherence among 26 African American and 42 European American pediatric renal transplant patients. Among both groups, perceived characteristics of their medication regimen, including pill size, pill taste and medication complexity, were found to have significantly low to moderate associations with medication adherence. These associations were stronger and more consistent across medication adherence measures among the African American patients. This supports the need to separately examine the factors contributing to medication adherence among ethnically different pediatric patients. Suggestions for promoting medication adherence among pediatric patients with renal transplants and implications for future research are discussed.