Collaborative Multidisciplinary Incident Command at Seattle Children's Hospital for Rapid Preparatory Pediatric Surgery Countermeasures to the COVID-19 Pandemic.

Washington was the first US state to have a patient test positive for COVID-19. Before this, our children's hospital proactively implemented an incident command structure that allowed for collaborative creation of safety measures, policies, and procedures for patients, families, staff, and providers. Although the treatment and protective standards are continuously evolving, this commentary shares our thoughts on how an institution, and specifically, surgical services, may develop collaborative process improvement to accommodate for rapid and ongoing change. Specific changes outlined include early establishment of incident command; personal protective equipment conservation; workforce safety; surgical and ambulatory patient triage; and optimization of trainee education. Please note that the contents of this manuscript are shared in the interest of providing collaborative information and are under continuous development as our regional situation changes. We recognize the limitations of this commentary and do not suggest that our approaches represent validated best practices.

Solid tumors following kidney transplantation in children.

Kidney transplant recipients have an increased risk of cancer. Data on non-LPD malignancies (solid tumors) in pediatric renal transplant recipients are limited. We performed a cohort study using the NAPRTCS transplant registry to describe the incidence of non-LPD malignancy compared with the general pediatric population. The observed incidence rate of non-LPD malignancy in the NAPRTCS transplant registry was 72.1 per 100,000 person-years (SIR 6.7; 95% CI, 5.3, 8.5); a 6.7-fold increased risk compared with the general pediatric population (10.7 cases per 100,000 person-years). Non-LPD malignancy was diagnosed in 35 subjects at a median of 726 days post-transplant. The most common type of malignancy was renal cell carcinoma. The increased risk of non-LPD malignancy was seen in all patients regardless of age, gender, race, etiology of end-stage kidney disease, and transplant era. The specific type of immunosuppression was not identified as a risk factor. In this first large-scale study of North American pediatric renal transplant recipients, we observed a 6.7-fold increased risk of non-LPD malignancy compared with the general pediatric population. Further examination of this unique patient population may provide greater insight into the impact of transplant and immunosuppression on malignancy risk.

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary.

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

BK virus nephropathy in pediatric renal transplant recipients: an analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry.

BACKGROUND AND OBJECTIVES: There is limited information regarding BK virus nephropathy in pediatric kidney transplantation. The objective of this study was to evaluate cases of BK virus nephropathy in the North American Pediatric Renal Trials and Collaborative Studies database. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a questionnaire that was sent to North American Pediatric Renal Trials and Collaborative Studies centers, we assessed the incidence, risk factors, clinical features, and outcomes of BK virus nephropathy in pediatric renal transplant recipients who received a transplant between 2000 and 2004. RESULTS: BK virus nephropathy was reported in 25 (4.6%) of 542 patients at a median onset of 10.1 mo after transplantation. The median age was 11 yr. All patients who were tested reported BK viruria, and 19 (91%) of 21 who had plasma tested reported BK viremia. Treatment of BK virus nephropathy included reduction of immunosuppression (84%), cidofovir (24%), leflunomide (8%), and intravenous Ig (20%). Simultaneous rejection treatment was reported in four (16%). The median creatinine was 2.0 mg/dl at a mean follow-up of 24 mo. There were six (24%) graft failures in the patients with BK virus nephropathy at a mean of 24 mo after diagnosis. Rejection occurred in eight (32%) after diagnosis. Multivariate analysis showed that use of polyclonal induction therapy and zero HLA DR mismatch were associated with the development of BK virus nephropathy. CONCLUSIONS: This first multicenter, retrospective, cohort study of BK virus nephropathy in pediatric renal transplant recipients found a BK virus nephropathy incidence of 4.6% and identified polyclonal induction and zero HLA DR mismatch as significant risk factors for BK virus nephropathy.

Adolescents are more likely to develop posttransplant lymphoproliferative disorder after primary Epstein-Barr virus infection than younger renal transplant recipients.

BACKGROUND: Primary Epstein-Barr virus (EBV) infection is the most important risk factor for development of posttransplant lymphoproliferative disorder (PTLD). Pediatric patients are often EBV seronegative pretransplant placing them at high risk. In the immune-competent population, primary herpesvirus infection is associated with higher morbidity with increasing age. METHODS: We performed a retrospective cohort study to describe the outcome of pediatric renal transplant recipients with primary EBV infection. All patients received 3 months of ganciclovir prophylaxis. Real-time quantitative polymerase chain reaction was used to determine the EBV viral load. Primary EBV infection was categorized as PTLD, symptomatic infection, or subclinical infection. RESULTS: There were a total of 46 patients with primary EBV infection: 11 developed PTLD, 12 had symptomatic infection, and 23 had subclinical infection. Adolescents were significantly more likely to develop PTLD than younger transplant recipients (P=0.05, chi-square). Multivariate analysis using logistic regression found that older age was the only significant risk factor for PTLD (odds ratio 1.24, 95% confidence interval 1.04-1.47; P=0.03). Among the 11 cases of PTLD, there were two deaths and two graft failures which all occurred in adolescent recipients (P=0.002). CONCLUSIONS: Among pediatric renal transplant recipients with primary EBV infection, adolescents are at significantly higher risk to develop PTLD and have poorer outcomes compared to younger recipients.

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.

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.

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.

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). 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

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.

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.

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.