Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy.

IgA nephropathy (IgAN) is associated with a risk for posttransplant recurrence. Data are limited regarding graft loss attributable to recurrence of IgAN among pediatric and young adult kidney transplant (KT) recipients. This was a retrospective cohort study of patients aged 0 to 25 years from the Scientific Registry of Transplant Recipients who received a primary KT for IgAN. Patients with history of KT attributable to renal dysplasia were comparators. Outcomes included the incidence of graft loss attributable to IgAN recurrence, association with donor type, and posttransplant corticosteroid use. In total, 5475 transplant recipients were included, with 1915 patients with IgAN and 3560 patients with renal dysplasia. In a multivariable Cox proportional hazards model, IgAN was associated with higher risk of graft loss (adjusted hazard ratio [aHR], 1.35; 95% CI, 1.21-1.50; P < .001) compared with dysplasia. Graft loss was attributed to recurrent disease in 5.4% of patients with IgAN. In a multivariable competing risks analysis, patients with IgAN receiving a parental living-donor kidney were more likely to report graft loss from recurrent disease compared with patients with a nonparental living donor (aHR, 0.52; 95% CI, 0.31-0.91; P = .02). Posttransplant prednisone use was not associated with improved graft survival (P = .2). These data challenge existing paradigms in posttransplant management of patients with IgAN.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy.

Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell-depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion. To study this, we screened for anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who received chimeric antigen receptor T-cell therapy (CARTx), targeting naïve and memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) for hematologic malignancies. Longitudinal samples were collected before and up to 1 year after CARTx. All individuals were in sustained remission. We identified 4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell depletion, anti-HLA antibodies and calculated panel reactive antibody scores were stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx low-level anti-HLA antibodies, with no follow-up samples available. These data implicate CD19neg long-lived plasma cells as an important source for anti-HLA antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx subjects receiving previous plasma cell-targeted therapies. Thus, plasma cell-targeted therapies may be more effective against HLA antibodies, thereby enabling improved access to organ transplantation and rejection management.

Contrast-enhanced voiding urosonography (CEVUS) as a safe alternate means of assessing vesicoureteral reflux in pediatric kidney transplant patients.

BACKGROUND: Although voiding cystourethrogram (VCUG) is currently the gold standard in VUR evaluation, there is ionizing radiation exposure. Contrast-enhanced voiding urosonography (CEVUS) uses ultrasound contrast agents to visualize the urinary tract and has been reported to be safe and effective in VUR evaluation in children. CEVUS application has yet to be specifically described in VUR evaluation in the pediatric kidney transplant population. The purpose of this study was to report the use of CEVUS and VCUG in evaluating and managing VUR in pediatric renal transplant patients. METHODS: Retrospective review was conducted for pediatric kidney transplant patients (18 years and younger) who underwent VCUG or CEVUS to assess for transplant VUR from July 2019 through June 2021. Demographic information, reason for VUR evaluation, fluoroscopy time, and postimaging complications were evaluated. Costs of imaging modalities were also considered. RESULTS: Eight patients were evaluated for transplant VUR during the study period. Of the 3 patients who underwent VCUG, all 3 had VUR (median grade 3). Median fluoroscopy time was 18 s and dose-area product was 18.7 uGy*m2 . Of the 5 patients who underwent CEVUS, 4 had VUR (median grade 4). There were no complications for either modality. Based on clinical and radiographic findings, patients were recommended no intervention, behavioral modification, or ureteral reimplantation. The total cost of CEVUS was $800 less than that of VCUG. CONCLUSION: CEVUS can provide an alternate means of safely evaluating VUR in kidney transplant patients with similar outcomes, potentially lower costs, and no exposure to ionizing radiation.

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients. METHODS: Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (18S-normalized CD3ε, CXCL10 mRNA, and 18S ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure. RESULTS: To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted. CONCLUSIONS: Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.

Benefits and risks of protocol biopsies in pediatric renal transplantation.

Protocol biopsies are defined as sampling of allograft tissue at predetermined times regardless of function. This procedure can be justified due to the lack of non-invasive methods to reliably diagnose rejection (acute or subclinical). Changes in creatinine are not seen with subclinical rejection or early acute rejection and do not always correlate with efficacy of treatment. Parents and providers are still hesitant to pursue protocol biopsy due to the potential complications and lack of definitive evidence of a benefit from doing this procedure. Importantly, the rate of transplant renal biopsy complications requiring additional intervention is low. It is unclear if detection and treatment of subclinical rejection detected on protocol biopsy will lead to improved graft survival. Our goal is to review the literature on this topic and share some of the experience in our center. Definition, indications, and complications of diagnostic transplant renal biopsies are not included in this review.

Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients.

BACKGROUND: The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear. METHODS: One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection. RESULTS: Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA. CONCLUSIONS: The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.

Prospective Assessment of Adenovirus Infection in Pediatric Kidney Transplant Recipients.

BACKGROUND: Adenovirus infection is associated with graft dysfunction and graft loss in pediatric cardiac, lung, and liver transplants in prior retrospective studies, but data in pediatric kidney transplant recipients is limited. METHODS: We conducted a prospective single-center cohort study of 75 consecutive pediatric kidney transplant recipients who underwent monthly screening for adenovirus viremia and symptom assessment for 2 years posttransplant. RESULTS: Adenovirus viremia was detected in 11 (14.7%) patients at a median onset of 173 days (interquartile range, 109-310 days) posttransplant, 6 (8%) had asymptomatic viremia, and 5 (6.7%) had symptomatic disease (2 with hematuria and 3 with an acute febrile respiratory illness). Viremic patients did not differ from nonviremic patients in age, immunosuppression management, or cytomegalovirus or Epstein-Barr virus serostatus, but were more likely to develop cytomegalovirus viremia during the first 2 years posttransplant. No patient had an increase in creatinine from baseline during the time of adenovirus viremia. In a Cox proportional hazards regression, subclinical adenovirus viremia was not associated with a faster time to a 30% decline in estimated glomerular filtration rate. CONCLUSIONS: Adenovirus infection is common among pediatric kidney transplant recipients and frequently causes symptomatic disease; however, symptoms are often mild and are not associated with a decline in graft function. Routine monitoring for adenovirus viremia in pediatric kidney transplant recipients may not be warranted.

Contribution of solid organ transplant recipients to the pediatric non-hodgkin lymphoma burden in the United States.

BACKGROUND: Pediatric solid organ transplant recipients have a 100 to 200 times higher risk of non-Hodgkin lymphoma (NHL) than the general pediatric population. Consequently, transplant-related NHL may contribute considerably to the pediatric NHL burden in the United States. METHODS: A cohort study using a linkage between the US transplant registry and 16 cancer registries was conducted. Cancer incidence rates were calculated for people less than 20 years old in the transplant and general populations. Rates were applied to transplant registry and US census data to estimate pediatric NHL counts for transplant recipients and the general population. RESULTS: During 1990-2012, an estimated 22,270 NHLs were diagnosed in US children and adolescents; they included 628 cases diagnosed in transplant recipients. Thus, 2.82% of pediatric NHL diagnoses in the general population (95% confidence interval [CI], 2.45%-3.19%) occurred in transplant recipients. Among transplant recipients, the most common subtypes were diffuse large B-cell lymphoma (DLBCL; 64.5% of cases) and Burkitt lymphoma (BL; 8.6%). For DLBCL and BL, transplant recipients contributed 7.62% (95% CI, 6.35%-8.88%) and 0.87% (95% CI, 0.51%-1.23%) of diagnoses, respectively. The proportion of NHLs that occurred in transplant recipients was highest among children less than 5 years old (4.46%; 95% CI, 3.24%-5.69%) and in more recent calendar years (3.73% in 2010-2012; 95% CI, 2.07%-5.39%). DLBCL patterns were similar, with transplant recipients contributing 19.78% of cases among children less than 5 years old (95% CI, 12.89%-26.66%) and 11.4% of cases in 2010-2012 (95% CI, 5.54%-17.28%). CONCLUSIONS: Among children and adolescents, solid organ transplant recipients contribute a substantial fraction of NHL diagnoses, particularly DLBCL diagnoses. This fraction has increased over time. Prevention efforts targeted toward this group could reduce the overall pediatric NHL burden. Cancer 2017;123:4663-4671. © 2017 American Cancer Society.

Cancer Risk After Pediatric Solid Organ Transplantation.

BACKGROUND: The effects of pediatric solid organ transplantation on cancer risk may differ from those observed in adult recipients. We described cancers in pediatric recipients and compared incidence to the general population. METHODS: The US transplant registry was linked to 16 cancer registries to identify cancer diagnoses among recipients <18 years old at transplant. Standardized incidence ratios (SIRs) were estimated by dividing observed cancer counts among recipients by expected counts based on the general population rates. Cox regression was used to estimate the associations between recipient characteristics and non-Hodgkin's lymphoma (NHL) risk. RESULTS: Among 17 958 pediatric recipients, 392 cancers were diagnosed, of which 279 (71%) were NHL. Compared with the general population, incidence was significantly increased for NHL (SIR = 212, 95% confidence interval [CI] = 188-238), Hodgkin's lymphoma (SIR = 19, 95% CI = 13-26), leukemia (SIR = 4, 95% CI = 2-7), myeloma (SIR = 229, 95% CI = 47-671), and cancers of the liver, soft tissue, ovary, vulva, testis, bladder, kidney, and thyroid. NHL risk was highest during the first year after transplantation among recipients <5 years old at transplant (SIR = 313), among recipients seronegative for Epstein-Barr virus (EBV) at transplant (SIR = 446), and among intestine transplant recipients (SIR = 1280). In multivariable analyses, seronegative EBV status, the first year after transplantation, intestine transplantation, and induction immunosuppression were independently associated with higher NHL incidence. CONCLUSIONS: Pediatric recipients have a markedly increased risk for many cancers. NHL constitutes the majority of diagnosed cancers, with the highest risk occurring in the first year after transplantation. NHL risk was high in recipients susceptible to primary EBV infection after transplant and in intestine transplant recipients, perhaps due to EBV transmission in the donor organ.

Cost Implications of New National Allocation Policy for Deceased Donor Kidneys in the United States.

BACKGROUND: In December 2014, a new national deceased donor kidney allocation policy was implemented, which allocates kidneys in the top 20% of the kidney donor profile index to candidates in the top 20% of expected survival. We examined the cost implications of this policy change. METHODS: A Markov model was applied to estimate differences in total lifetime cost of care and quality-adjusted life years (QALY). RESULTS: Under the old allocation policy, average lifetime outcomes per listed patient discounted to 2012 US dollars were US $342,799 and 5.42 QALY, yielding US $63,775 per QALY gained. Under the new policy, average lifetime cost was reduced by US $2090 and lifetime QALYs increased by 0.03. Thus, the new policy improved on the old policy by producing more QALYs at lower cost. The present value of total lifetime cost savings from the policy change is estimated to be US $271 million in the first year and US $55 million in subsequent years. The higher transplant rates and allograft survival expected for candidates in the top 20% of expected survival would decrease costs by reducing time on dialysis. Most cost savings are expected to accrue to Medicare, and most increased access to transplant is expected in private payer populations. CONCLUSIONS: The new allocation policy was found to be dominant over the old policy because it increases QALYs at lower cost.

The dynamics of apoplast phenolics in tobacco leaves following inoculation with bacteria.

This study demonstrates that the accumulation of apoplastic phenolics is stimulated in planta in response to bacterial inoculation. Past studies have shown that levels of extracellular phenolics are elicited in plant cell suspensions in response to bacteria, and that tomato plants infected with viroids showed changes in apoplastic phenolics. The method described here monitored changes in apoplastic phenolics in tobacco leaves following bacterial inoculation of the same tissue. Inoculation with a saprophyte, Pseudomonas fluorescens, which does not cause visible symptoms or physical damage, was used to elicit phenolics and examine the effects of variable parameters on phenolic composition. Location of the inoculation on the leaf, position, or developmental age of the leaf on the plant, and inoculum concentration were standardized for further experiments. The patterns of phenolic change in the apoplast were compared for tobacco inoculated with P. syringae pathovars, pv. syringae, which causes a resistant HR reaction within 15 h, and pv. tabaci, which causes a susceptible reaction with delayed visible symptoms. Both pathogens elicited lower increased levels of acetosyringone compared to the saprophyte, P. fluorescens but had greatly increased levels of the chlorogenic acid derivatives. The latter metabolites appear to have come from the intracellular stores, which could indicate a weakening of the apoplast/symplast barrier. This unexpected aspect will require further study of intracellular phenolics.

Choosing the order of deceased donor and living donor kidney transplantation in pediatric recipients: a Markov decision process model.

BACKGROUND: Most pediatric kidney transplant recipients eventually require retransplantation, and the most advantageous timing strategy regarding deceased and living donor transplantation in candidates with only 1 living donor remains unclear. METHODS: A patient-oriented Markov decision process model was designed to compare, for a given patient with 1 living donor, living-donor-first followed if necessary by deceased donor retransplantation versus deceased-donor-first followed if necessary by living donor (if still able to donate) or deceased donor (if not) retransplantation. Based on Scientific Registry of Transplant Recipients data, the model was designed to account for waitlist, graft, and patient survival, sensitization, increased risk of graft failure seen during late adolescence, and differential deceased donor waiting times based on pediatric priority allocation policies. Based on national cohort data, the model was also designed to account for aging or disease development, leading to ineligibility of the living donor over time. RESULTS: Given a set of candidate and living donor characteristics, the Markov model provides the expected patient survival over a time horizon of 20 years. For the most highly sensitized patients (panel reactive antibody > 80%), a deceased-donor-first strategy was advantageous, but for all other patients (panel reactive antibody < 80%), a living-donor-first strategy was recommended. CONCLUSIONS: This Markov model illustrates how patients, families, and providers can be provided information and predictions regarding the most advantageous use of deceased donor versus living donor transplantation for pediatric recipients.

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.

Order of donor type in pediatric kidney transplant recipients requiring retransplantation.

BACKGROUND: Living-donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased-donor KT. Despite this, there has been a steady decrease in the use of living-donor KT for pediatric recipients. Due to their young age at transplantation, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear. METHODS: Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987 and 2010. RESULTS: Living-donor grafts had longer survival compared with deceased-donor grafts, similarly among both first (adjusted hazard ratio [aHR], 0.78; 95% confidence interval [CI], 0.73-0.84; P<0.001) and second (aHR, 0.74; 95% CI, 0.64-0.84; P<0.001) transplants. Living-donor second grafts had longer survival compared with deceased-donor second grafts, similarly after living-donor (aHR, 0.68; 95% CI, 0.56-0.83; P<0.001) and deceased-donor (aHR, 0.77; 95% CI, 0.63-0.95; P=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased-donor and living-donor transplantation. CONCLUSIONS: Deceased-donor KT in pediatric recipients followed by living-donor retransplantation does not negatively impact the living-donor graft survival advantage and provides similar cumulative graft life compared with living-donor KT followed by deceased-donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased-donor waiting times.

Practice patterns and outcomes in retransplantation among pediatric kidney transplant recipients.

BACKGROUND: More than 25% of pediatric kidney transplants are lost within 7 years, necessitating dialysis or retransplantation. Retransplantation practices and the outcomes of repeat transplantations, particularly among those with early graft loss, are not clear. METHODS: We examined retransplantation practice patterns and outcomes in 14,799 pediatric (ages <18 years) patients between 1987 and 2010. Death-censored graft survival was analyzed using extended Cox models and retransplantation using competing risks regression. RESULTS: After the first graft failure, 50.4% underwent retransplantation and 12.1% died within 5 years; after the second graft failure, 36.1% underwent retransplantation and 15.4% died within 5 years. Prior preemptive transplantation and graft loss after 5 years were associated with increased rates of retransplantation. Graft loss before 5 years, older age, non-Caucasian race, public insurance, and increased panel-reactive antibody were associated with decreased rates of retransplantation. First transplants had lower risk of graft loss compared with second (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.64-0.80; P<0.001), third (aHR, 0.62; 95% CI, 0.49-0.78; P<0.001), and fourth (aHR, 0.44; 95% CI, 0.24-0.78; P=0.005) transplants. However, among patients receiving two or more transplants (conditioned on having lost a first transplant), second graft median survival was 8.5 years despite a median survival of 4.5 years for the first transplant. Among patients receiving three or more transplants, third graft median survival was 7.7 years despite median survivals of 2.1 and 3.1 years for the first and second transplants. CONCLUSIONS: Among pediatric kidney transplant recipients who experience graft loss, racial and socioeconomic disparities exist with regard to retransplantation, and excellent graft survival can be achieved with retransplantation despite poor survival of previous grafts.

Anemia and risk of hospitalization in pediatric chronic kidney disease.

BACKGROUND AND OBJECTIVES: Anemia is a well known complication of chronic kidney disease (CKD); however, the prevalence of anemia within CKD stages in the pediatric population has not been established. Additionally, the associated morbidity of anemia in the pediatric CKD population has not been elucidated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 2,779 patients ages 2 yr and older in the North American Pediatric Renal Trials and Collaborative Studies database with CKD stage II to V (excluding dialysis or previous transplant patients) were identified. Descriptive statistics and multivariate modeling using logistic regression was performed to determine the prevalence of anemia and to evaluate the correlation between baseline anemia and hospitalization. RESULTS: The prevalence of anemia (hematocrit < 33%) increased from 18.5% in CKD stage II to 68% in CKD stage V (predialysis). Anemic children were 55% more likely to be hospitalized when compared with nonanemic children (odds ratio 1.55; 95% confidence interval 1.23 to 1.94). Similar results were obtained using hematocrit cutoffs of 36 and 39%. CONCLUSIONS: In this pediatric predialysis CKD population, anemia increases with increasing CKD stage and is significantly associated with hospitalization risk. Hematocrit levels above 36 and 39% were not associated with increased risk of hospitalization. Further examination into the effect of correcting anemia on hospitalization rates may provide additional useful information.

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.