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Biomedical subjects

Ruth A McDonald

Publications and source records attributed to Ruth A McDonald.

18 recordsLinked to original sources
PubMed2006

Sonic tooth brushing reduces gingival overgrowth in renal transplant recipients.

Cyclosporine (CSA) is a commonly used immunosuppressive medication in pediatric transplantation. Drug-induced gingival overgrowth (DIGO) is a frequent side effect associated with CSA use and can impair the patient's ability to achieve good oral hygiene. This study tested the hypothesis that sonic tooth brushing and oral hygiene instruction can reduce the occurrence or severity of DIGO in CSA-treated pediatric renal transplant recipients. Twenty-three pediatric renal transplant patients with DIGO were randomly allocated to treatment or control groups. The treatment group received oral hygiene instruction and use of a sonic toothbrush, while the control group continued their usual home care with manual brushes. Dental impressions and photographs of all subjects were taken at baseline and every 3 months for a year. The casts and photographs were evaluated by a dental panel to compare the DIGO levels from baseline until the end of the study. After 12 months the control group had significantly more severe DIGO than did the sonic tooth brushing and oral hygiene instruction group (OR=4.5, 95%CI=1.2-16.0, P=0.03). Of the risk factors considered, only male gender was significantly associated with worse outcome (OR=6.1, 95%CI=2.3-16.1, P=0.03). The use of a powered toothbrush, together with oral hygiene instruction, may be an important component of health maintenance for pediatric transplant patients on CSA.

Adolescent↗
PubMed2006

Risk of lymphoma after renal transplantation varies with time: an analysis of the United States Renal Data System.

BACKGROUND: Characterization of the incidence of posttransplant lymphoma over time may help guide the timing and intensity of posttransplant monitoring. We analyzed the United States Renal Data System to describe the occurrence of lymphoma following renal transplantation. METHODS: All end-stage renal disease patients placed on the transplant waiting list between January 1, 1990 and December 31, 1999 were considered. Survival analysis was used to estimate lymphoma risk in renal transplant patients. RESULTS: Of 89,260 eligible patients, a total of 556 lymphoma cases were identified with 357 in transplant patients. The overall rate of posttransplant lymphoma was 33.3/10,000 person-years in transplant patients. There was variation in the duration and magnitude of increased lymphoma risk by age. The highest rates of lymphoma were among transplanted patients in the first 12 months, after which the rate of lymphoma decreased. Among Caucasian transplant recipients less than 25 years of age, the adjusted relative risk of lymphoma ranged from 13.82 [95% CI: (3.96, 48.15)] within 6 months posttransplant to 3.46 [95% CI: (0.69, 17.44)] within months 30-36 posttransplant. Only patients under 25 years had a notably increased risk beyond the first 2 posttransplant years. The risk of lymphoma differed by race, with Caucasian patients at nearly double the risk of African-Americans. Gender was not associated with lymphoma incidence. CONCLUSIONS: We found and quantified a time-varying relationship between renal transplant and lymphoma risk. This information can be used in combination with knowledge of established risk factors to guide the schedule of posttransplant monitoring.

Adult↗
PubMed2006

Emerging viral infections in transplantation.

Viral infections are an important complication of transplantation. The introduction of more potent immunosuppressive agents over the past decade correlates with an increase in the rate of hospitalizations of transplant patients with infections. Specifically, viral infections have emerged as a major source of morbidity and mortality in transplantation. There are several potential intervention strategies in the face of emerging infections and it is likely that the approach will differ depending on the virus in question. These include viral surveillance and pre-emptive therapy, intervention of the transplant community, and policy change at the level of government, blood bank and organ procurement organizations. This review focuses on the emergence of the herpesviruses; HHV-6 and HHV-7. In addition, the issue of virus transmission through organ transplant is addressed with a discussion of West Nile virus and the rabies virus.

Antiviral Agents↗
PubMed2006

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.

Adolescent↗
PubMed2005

Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation.

PURPOSE: To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) -positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD. PATIENTS AND METHODS: Eligible patients received cyclophosphamide (600 mg/m2 intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles. RESULTS: Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had > or = three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively. CONCLUSION: This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.

Adolescent↗
PubMed2005

Renal transplantation in adolescents.

Renal transplantation remains the goal for the pediatric patient with end-stage renal disease. Recent advances in technology and immunosuppression have greatly enhanced patient and graft survival, while reducing significant complications. However, transplantation of adolescents is still fraught with the potential for serious problems. The increased risk of graft loss, late acute rejection, and incomplete rejection reversal observed in the adolescent age group demands further investigation. Lack of adherence to immunosuppression regimens may be an important contributory factor. Strategies to address the unique concerns of this high-risk population, including the use of a multidisciplinary team, are essential to improving outcomes.

Adolescent↗
PubMed2005

Pediatric transplantation, 1994-2003.

This article uses OPTN/SRTR data to review trends in pediatric transplantation over the last decade. In 2003, children younger than 18 made up 3% of the 82,885 candidates for organ transplantation and 7% of the 25,469 organ transplant recipients. Children accounted for 14% of the 6,455 deceased organ donors. Pediatric organ transplant recipients differ from their adult counterparts in several important aspects, including the underlying etiology of organ failure, the complexity of the surgical procedures, the pharmacokinetic properties of common immunosuppressants, the immune response following transplantation, the number and degree of comorbid conditions, and the susceptibility to post-transplant complications, especially infectious diseases. Specialized pediatric organ transplant programs have been developed to address these special problems. The transplant community has responded to the particular needs of children and has provided them special consideration in the allocation of deceased donor organs. As a result of these programs and protocols, children are now frequently the most successful recipients of organ transplantation; their outcomes following kidney, liver, and heart transplantation rank among the best. This article demonstrates that substantial improvement is needed in several areas: adolescent outcomes, outcomes following intestine transplants, and waiting list mortality among pediatric heart and lung candidates.

Adolescent↗
PubMed2004

Risk factors for catheter-related complications in pediatric peritoneal dialysis.

Catheter-related complications, including infection, dialysate leak, and malfunction, are the principal causes of peritoneal dialysis (PD) failure. To determine risk factors predisposing to these complications, we conducted a retrospective study of 90 children on chronic PD who received 127 catheters from January 1990 to December 2000. There was a significant risk for dialysate leak when PD catheters were used early (</=14 days post placement) versus delayed use (>14 days). There was no significant difference in malfunction and infection rate between early and delayed use groups. Weight and height <5th percentile, low serum albumin, and history of abdominal surgery were not associated with an increased risk of complications. History of dialysis prior to catheter placement and presence of a gastrostomy tube (G-tube) were both associated with significant infection risk. Patients </=3 years old were more likely to have a G-tube and had an increased risk of infection. We conclude that delayed use of the PD catheter led to a lower incidence of dialysate leak but had no effect on infection rate. Young age, G-tube, and history of prior dialysis are risk factors for infection. Multi-center, prospective controlled studies involving larger numbers of children are important to confirm these findings.

Adolescent↗
PubMed2004

Expression of nephrin in acquired forms of nephrotic syndrome in childhood.

Nephrin is a podocyte adhesion molecule located at the slit diaphragm between adjacent glomerular epithelial cells. Mutations in the gene encoding nephrin result in the absence of nephrin or alterations in nephrin causing massive proteinuria in patients with congenital nephrotic syndrome. Given the importance of nephrin to the structural integrity of the glomerular filtration barrier, we postulated that it might also be altered in acquired forms of nephrotic syndrome (NS). To test this hypothesis, frozen kidney biopsy sections from 29 pediatric patients with acquired NS and 5 controls were examined for expression of nephrin. The pathological diagnoses were minimal change disease (MCNS) (19) and focal segmental glomerulosclerosis (FSGS) (10). To determine if nephrin expression differed between children and adults with NS, 10 adult patients and 3 controls were also examined. Nephrin expression was evaluated by immunoperoxidase staining with a monoclonal antibody against the extracellular FnIII portion of human nephrin. In all cases, nephrin expression was seen along the glomerular basement membrane in a finely granular/linear pattern. Expression of nephrin was similar to controls in all 19 patients with MCNS and all 10 patients with FSGS. Areas of sclerosis in patients with FSGS did not demonstrate nephrin expression. A distinctly granular pattern to nephrin expression was seen in adult patients with NS as well as controls. These findings suggest that an alteration in nephrin expression is not a feature of acquired forms of NS in childhood.

Adolescent↗
PubMed2004

Polyomavirus nephropathy in pediatric kidney transplant recipients.

Given the limited information regarding BK virus-associated nephropathy (BKVN) in pediatric kidney transplant recipients, we assessed the incidence, risk factors, clinical and virologic features of BKVN in pediatric renal transplant recipients at a single transplant center by means of a retrospective cohort study. Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant recipients at a median of 15 months post-transplant (range: 4-47 months). At a median follow-up of 28 months (range: 5-32), all patients had functioning grafts with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL, range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL, range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was significantly associated with the development of BKVN (p = 0.01). BKVN is an important cause of late allograft dysfunction and is strongly associated with recipient seronegativity in pediatric kidney transplant recipients. Further studies to confirm this finding and to define the clinical utility of routine pre-transplant BKV serologic testing are warranted.

Adolescent↗
PubMed2003

Current immunosuppressive agents: efficacy, side effects, and utilization.

Advances in immunosuppressive therapy over the past decade have led to dramatic improvements in graft survival. With the development of new agents, the focus of the transplant community is to establish regimens that maintain excellent graft survival rates but with fewer toxicities including infection, nephrotoxicity, malignancy, and cosmetic effects. Examples include the use of steroid-free protocols and calcineurin avoidance regimens, which are currently being studied by NAPRTCS. The ultimate goal of transplant immunosuppressive therapy is the induction of tolerance. As we learn more about immune function from basic and clinical research, tolerance to allografts seems a more reachable goal.

Abatacept↗
PubMed2003

Changing trends in pediatric transplantation: 2001 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The North American Pediatric Renal Transplant Cooperative Study has collected clinical information on children undergoing a renal transplantation since 1987. This cooperative group now includes over 150 participating medical centers in the United States, Canada, Mexico, and Costa Rica. This report covers the years from 1987 through 2001 and includes data on 7545 renal transplants in 6878 patients. This report demonstrates changing trends in many areas of pediatric transplantation including increasing numbers of African American and Hispanic children receiving transplantation, remarkable improvements in the rate of acute rejection, rejection reversal, and short- and long-term allograft survival. In the most recent cohorts of patients, we now see that 1-yr allograft survival is no different in cadaver donor compared to living donor recipients and in infants compared to all other age groups. However, this analysis also reveals areas of continued challenges including inferior outcomes in African American and adolescent populations, chronic rejection, and the adverse effects of immunosuppression.

Black People↗
PubMed2003

Pretransplant peritoneal dialysis and graft thrombosis following pediatric kidney transplantation: a NAPRTCS report.

Graft thrombosis is a common cause of graft failure in pediatric renal transplantation. Several previous studies, including a North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) review of pretransplant dialysis status and graft outcomes, have described a potential correlation of peritoneal dialysis (PD) and graft thrombosis. This issue is of particular concern for pediatric transplant programs as more than 65% of children with end stage renal disease are treated with PD. We reviewed 7247 pediatric renal transplants performed between 1987 and 2001. Thrombosis was the cause of graft loss in 2.7% (199) of all the transplants performed. Among failed transplants, thrombosis was the third most common cause of graft loss in both index (11.6%) and subsequent transplants (14.5%). Thrombosis becomes the most common cause of graft failure (21%, 61/294) if one looks at transplants in the later cohort, from 1996 to 2001. This change is primarily because of a decrease in the incidence of acute rejection. In the PD group, 3.4% of all grafts were lost as a result of thrombosis. This compares with 1.9% in the hemodialysis group, 2.4% in the pre-emptive transplant group, and 4.1% among patients who received both dialysis modalities. There was a statistically significant difference in thrombosis failure risk in the different dialysis groups (p = 0.005) with those who received only peritoneal dialysis having the highest risk. Additional significant risk factors for graft thrombosis included; cadaver donor source (p < 0.001), cold ischemia time >24 h (p < 0.001), history of prior transplant (p < 0.001), donor age <6 yr (p < 0.001), and >5 pretransplant blood transfusions (p = 0.02). Using stepwise proportional hazards modeling, only pretransplant peritoneal dialysis, >24 h cold ischemia time, prior transplant, and donor age <6 yr were simultaneously associated with an increased risk of thrombosis. We conclude that pretransplant PD is associated with an increased risk of graft thrombosis. Special precautions should be undertaken in pediatric renal transplant patients who have received PD, especially infants and young children.

Child↗
PubMed2002

Peritonitis due to Leuconostoc species in a child receiving peritoneal dialysis.

Leuconostoc species are rarely pathogenic in humans, but may cause infection in patients at risk. A 7-year-old girl with p-ANCA-positive crescentic glomerulonephritis, treated with peritoneal dialysis, developed peritonitis due to Leuconostoc species. She had a history of treatment with vancomycin and a brief course of immunosuppressive therapy. The peritonitis responded well to ampicillin therapy. To date, only 47 cases of Leuconostoc infection, including our patient, have been reported in the medical literature; 25 of the cases occurred in children. Only 1 prior case has been reported in the setting of peritoneal dialysis. The risk factors for Leuconostoc infections are not clear, but commonly associated conditions include immunocompromised status and indwelling medical devices. Leuconostoc species are easily misidentified as streptococci in culture, but they possess inherent resistance to vancomycin despite sensitivity to most other antibiotics. In patients with gram-positive peritonitis, Leuconostoc should be considered as a possible etiological agent, particularly if vancomycin resistance is noted in an organism thought to be a Streptococcus species.

Ampicillin↗
PubMed2002

Chronic dialysis in children and adolescents. The 2001 NAPRTCS Annual Report.

The 2001 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry includes data on 4,546 dialysis patients. Important trends in dialysis care include a significant increase in the use of peritoneal dialysis catheters with two cuffs (51.6% vs. 36.2%, P<0.001), a Swan neck tunnel (34.1% vs. 20.9%, P<0.001), and a downward pointing exit site (34.9% vs. 29.5%, P<0.001) in patients who initiated dialysis between 1997 and 2000 compared with 1992-1996. Most hemodialysis patients continued to have an external percutaneous catheter as their access at the time of initiation of dialysis (1,550/1,971 patients, 78.6%), but the odds of using a jugular rather than a subclavian vein for these catheters increased by 24% each year between 1992 and 2000. There was a significant trend for increasing use of erythropoietin and by 1996, 96% of patients were prescribed this medication at initiation of dialysis. There was also a modest, but significant, increase in hematocrit in the dialysis registry, as the median hematocrit at 6 months of follow-up was 31% in patients who started dialysis between 1997 and 2000 ( P<0.001).

Adolescent↗
PubMed2002

A 14-year-old girl with recumbent proteinuria.

We describe a 14-year-old female who presented with persistently elevated nighttime urinary protein excretion without additional clinical symptoms. She had no evidence of intrinsic renal disease on physical examination or laboratory studies. Ultrasound examination of the abdomen revealed a large cyst arising from the spleen. CT scan showed compression of the left renal vein by the splenic cyst. Removal of the cyst resulted in resolution of her proteinuria. Entrapment of the left renal vein (nutcracker syndrome) remains a rare but important cause of elevated protein excretion.

Adolescent↗
PubMed2002

Renal transplant outcomes in adolescents: a report of the North American Pediatric Renal Transplant Cooperative Study.

Recipient age at transplant is an important predictor of outcome. The age most commonly associated with increased risk is infancy. An important, but less recognized, age group at high risk is the adolescent. We analyzed the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database to determine the patient and graft outcomes of adolescents (13-17 yr of age) compared with younger children. The adolescent age group had a similar percentage patient survival rate compared to that of the younger age groups, except for the infants (0-1 yr), who had a dramatic drop-off in the early post-transplant period. Regarding the long-term graft survival for living donor recipients, adolescents had the poorest percentage graft survival compared to the other age groups, including the infants (p < 0.001). Among cadaver donor recipients, the adolescent group had a significantly poorer graft survival than the 2-5 yr and 6-12 yr age groups (p < 0.001). Although the infants had the poorest graft survival (p < 0.001), after the sharp drop-off in the immediate post-transplant period the slope of their graft-survival curve was similar to that of the 13-17 yr age group. The percentage of late acute rejection episodes among the 6-12 yr (26.0%) and 13-17 yr (22.2%) age groups was significantly higher than in the younger age groups (p < 0.001). The adolescents had relatively poor rejection reversal outcomes compared to the other age groups, with fewer complete rejection reversals and a greater number of partial reversals (p < 0.001). The increased risk of graft loss, late acute rejection, and incomplete rejection reversal observed in the adolescent age group demands further investigation. Lack of compliance with immunosuppression regimens may be an important contributory factor. Strategies to address the unique concerns of this high-risk population will be essential to improve outcomes.

Adolescent↗