Hypogammaglobulinemia in pediatric kidney transplant recipients.

Infections remain the most common cause of hospitalization after kidney transplantation, contributing to significant post-transplant morbidity and mortality. There is a growing body of literature that suggests that immunoglobulins may have a significant protective role against post-transplant infections, although the literature remains sparse, inconsistent, and not well publicized among pediatric nephrologists. Of great concern are data indicating a high prevalence of immunoglobulin abnormalities following transplantation and a possible link between these abnormalities and poorer outcomes. Our educational review focuses on the epidemiology and risk factors for the development of immunoglobulin abnormalities after kidney transplantation, the outcomes in patients with low immunoglobulin levels, and studies evaluating possible interventions to correct these immunoglobulin abnormalities.

Tidal continuous cycling peritoneal dialysis in children.

About 10% of all home peritoneal dialysis regimens in children with chronic kidney disease stage 5 are reported to involve some form of a tidal peritoneal dialysis (TPD) prescription. Despite this, there remain several gaps in how pediatric nephrologists approach the use of TPD. This stems from a combination of factors such as the confusing technical terminology pertaining to TPD, seemingly conflicting data on the risks, benefits, and indications for TPD, and lastly, limited published guidelines on the practical aspects of how to write a TPD prescription, based on the indication, in children. Our educational review, using evidence-based data, attempts to bridge this gap and provide an easy-to-use guide on the key practical aspects of TPD in children.

Outcomes of living unrelated donor kidney transplants in children: An Organ Procurement and Transplant Network database analysis.

BACKGROUND: There are conflicting data on long-term outcomes of pediatric LURD renal Txs compared to Txs of kidneys from other donor sources. METHODS: An analysis of the OPTN database was conducted in children (<18 years) who had received their 1st kidney-only Tx between January 1, 2000, and September 30, 2021. The primary outcome measure was time to graft failure or death. Cox event history regression model for time to primary outcome, categorized by donor source and adjusting for confounders was performed. RESULTS: Of the 12 089 subjects, 327 (2.7%) received kidneys from LURDs, 4349 (36%) from LRDs and 7413 (61%) from DD. One year graft failure rate was 3.56%. On regression analyses, compared to LRD kidney recipients, LURD recipients had comparable graft survival (graft failure AHR 1.15, 95th percentile confidence interval 0.87-1.51; p .31) and DD recipients had lower graft survival (graft failure hazard ratio 1.26, 95th percentile confidence interval 1.10-1.43; p < .001). When using living unrelated kidney recipients as the reference group, DD kidney recipients had comparable graft survival, with a wide confidence interval (hazard ratio for graft failure 1.09; 0.83-1.43, p .53). CONCLUSIONS: Pediatric LURD kidney recipients have comparable graft survival to LRD kidney recipients; DD kidney recipients had the poorest survival. Our study, the largest to date, should encourage centers to embrace non-commercial living-unrelated transplantation as a viable option for children, preferable to DD kidneys.

Diabetic kidney disease in children and adolescents: an update.

Diabetic kidney disease (DKD), previously encountered predominantly in adult patients, is rapidly gaining center stage as a childhood morbidity and one that pediatric nephrologists are likely to encounter with increasing frequency. This is in large part due to the obesity epidemic and the consequent rise in type 2 diabetes in children and adolescents, as well as the more aggressive diabetes phenotype in today's youth with more rapid ß-cell decline and faster development and progression of diabetes-related complications along with lower responsiveness to the treatments used in adults. DKD, an end-organ complication of diabetes, is at the very least a marker of, and more likely a predisposing factor for, the development of adverse cardiovascular outcomes and premature mortality in children with diabetes. On an optimistic note, several new therapeutic approaches are now available for the management of diabetes in adults, such as GLP1 receptor agonists, SGLT2 inhibitors, and DPP4 inhibitors, that have also been shown to have a favorable impact on cardiorenal outcomes. Also promising is the success of very low-energy diets in inducing remission of diabetes in adults. However, the addition of these pharmacological and dietary approaches to the management toolbox of diabetes and DKD in children and adolescents awaits thorough assessment of their safety and efficacy in this population. This review outlines the scope of diabetes and DKD, and new developments that may favorably impact the management of children and young adults with diabetes and DKD.

Exploring how national educational organizations can promote educational research amongst members: a survey-based study.

BACKGROUND: Engagement of academic faculty in research remains low. While barriers to research have been explored, there are no data on how national organizations can help overcome these barriers. Our study explored faculty satisfaction and motivational drivers for engagement with research opportunities offered by the Council on Medical Student Education in Pediatrics (COMSEP), an organization of pediatric medical educators, and characterize strategies perceived by faculty to promote the use of these opportunities. METHODS: In 2021, 5 survey questions were administered to faculty members of COMSEP to explore satisfaction with COMSEP's research offerings, the perceived value of educational research, and the facilitators, barriers and potential opportunities for COMSEP to promote research. Clark's Commitment and Necessary Effort model on motivation served as the theoretical framework for our study, which explores motivation, self-efficacy and contextual factors influencing an individual's pursuit of goals. Chi-square analysis and Wilcoxon Signed Ranks Test were used to compare categorical and scaled variables among groups who did and did not avail of COMSEP's research offerings. RESULTS: 90 (25%) of 360 recipients responded. 61% expressed satisfaction with COMSEP's research offerings. 68% indicated research was an expectation of their academic appointment, that education was their primary research focus (74%) and that they did not have other research opportunities that met their needs (58%). Of respondents, 75.7% of females had submitted a proposal compared to 60% of non-responders who were females. The comparison by gender was not statistically significant. Exploration by academic rank revealed that 35% of instructor/assistant professors had submitted a proposal compared to 65% of associate professors/professors (p =.05). Barriers leading to non-submission to any of the offerings included having too much other work, lack of enjoyment in writing and inability to find mentors. Respondents endorsed the importance of several strategies to promote engagement in research-skill building opportunities, personalized consultations and increased funding. CONCLUSIONS: Faculty educators value the importance of educational research and recognize that research opportunities offered by COMSEP address an unmet need, but express ambivalence in the enjoyment of writing (reflecting their mood), and endorse structural barriers, that are amenable to change, affecting their personal agency.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

Intravenous cyclophosphamide induces remission in children with difficult to treat steroid resistant nephrotic syndrome from minimal change disease.

BACKGROUND: Steroid resistant nephrotic syndrome (SRNS), while uncommon in children, is associated with significant morbidity. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS, but some children fail to respond to them. Intravenous (IV) cyclophosphamide (CTX) has been shown to be effective in Asian-Indian children with difficult to treat SRNS (SRNS-DTT). Our study evaluated the outcome of IV CTX treatment in North American children with SRNS-DTT. METHODS: Retrospective review of the medical records of children with SRNS-DTT treated with IV CTX from January 2000 to July 2019 at our center. Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents and serial clinical/laboratory data. Primary outcome measure was attainment of complete remission (CR). RESULTS: Eight children with SRNS-DTT received monthly doses (median 6; range 4-6) of IV CTX. Four (50%) went into CR, 1 achieved partial remission and 3 did not respond. Three of the 4 responders had minimal change disease (MCD). Excluding the 1 child who responded after the 4th infusion, the median time to CR was 6.5 (range 0.5-8) months after completion of IV CTX infusions. Three remain in CR at a median of 8.5 years (range: 3.7-10.5 years) after completion of CTX; one child relapsed and became steroid-dependent. No infections or life-threatening complications related to IV CTX were observed. CONCLUSIONS: IV CXT can induce long term remission in North-American children with MCD who have SRNS-DTT.

Establishing an educational value unit to promote teaching in an academic unit.

Background: In academic health centers, education remains an incompletely supported and funded mandate. In an attempt to promote education and better support educational endeavors of faculty, some academic health centers and departments have conceived of a metric, the educational value unit (eVU), to begin to "quantify" teaching. What goes into this metric, its intended goals and the logistics of its implementation vary considerably among centers. Lessons Learned: This practical advice paper highlights the various lessons learned from a review of the limited published literature on eVU systems supplemented with our personal experience in implementing a successful eVU system in the Department of Pediatrics at our institution, to help guide others who may be interested in doing that same. Even in limited-resource settings, our hope is that these lessons can serve as a guide on how to better quantify and reward teaching, whether through monetary or nonfiscal incentives and recognition.

Predictors of time to first cannulation for arteriovenous fistula in pediatric hemodialysis patients: Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.

Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

BACKGROUND: Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of primary and secondary patency of PVA in pediatric HD patients. METHODS: Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome. RESULTS: There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (p = 0.0391) and secondary patency (p = 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (p = 0.0252) and directly correlated with overall survival of AVF (p = 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (p = 0.0082), but not number of complications or interventions, or outcomes. CONCLUSIONS: In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.

Correction to: Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.

Illuminating exemplary professionalism using appreciative inquiry dialogues between students and mentors.

PURPOSE: To explore the types of exemplary professional behaviors and the facilitators and barriers to professional behavior discussed by student-mentor dyads during appreciative inquiry (AI) dialogs. MATERIALS AND METHODS: We conducted a qualitative analysis of AI narratives discussing exemplary professional practice written by third-year medical students following a dialog with mentors. Narratives were thematically analyzed using directed content analysis to explore the types of exemplary professional behaviors discussed and the facilitators and barriers to professional practice. Narratives were coded independently by two investigators; codes were finalized, themes were derived, and a model on how exemplary professional behaviors are nurtured and reinforced was developed. RESULTS: Themes addressed humanism toward others and excellence, with altruism being an underlying implicit guiding principle behind professional behavior. Humanism toward self was infrequently discussed as an aspect of professionalism, but when discussed, was perceived to foster resilience. Principle-based attitudes and emotional intelligence facilitated professional behaviors. Programmatic scaffolds facilitated professional behavior and included curricula on reflective practice, mentorship, promoting learner autonomy and connectedness, and a safe environment. CONCLUSIONS: AI is an effective strategy that can be used to stimulate learner reflection on professionalism, humanism, and wellness and promote learner acknowledgement of positive aspects of the learning environment.

Effect of BMI on allograft function and survival in pediatric renal transplant recipients.

OBJECTIVE: To determine whether pre-transplant body mass index (BMI) affects renal allograft function and survival in pediatric renal transplant recipients. STUDY DESIGN: This is a retrospective cohort study using the Organ Procurement and Transplantation Network data from 2000 to 2013 to compare time to total allograft loss (allograft failure or death), prevalence of delayed graft function, prevalence of acute rejection, and estimated glomerular filtration rate (eGFR) post-transplant in pediatric renal transplant recipients categorized by BMI z-score. RESULTS: A total of 8804 kidney transplant recipients met our inclusion criteria, and of those, 6% were underweight, 14% were overweight, and 17% were obese pre-transplant. The adjusted hazard ratio (HR) for allograft failure was significantly higher for obese recipients compared to normal weight recipients (HR 1.25, 95% CI 1.1, 1.42); for every 1 point increase in BMI z-score, there was a 7% increased hazard of allograft failure (HR 1.07; 95% CI 1.03-1.1, p < 0.001). The prevalence of delayed graft function and acute rejection increased with higher BMI z-score category; however, this difference did not reach statistical significance. eGFR at 1 and 5 years post-transplant decreased with higher BMI z-score although it was only statistically significant at 1 year. CONCLUSIONS: Obesity is prevalent in pediatric renal transplant recipients, and obese, but not overweight or underweight, pediatric renal transplant recipients have an increased risk of allograft failure. Implementation of effective obesity interventions in pediatric renal transplant recipients is of critical importance to improve longevity of the renal allograft.

Hypersensitivity reactions in patients receiving hemodialysis.

OBJECTIVE: To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. DATA SOURCES: PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. STUDY SELECTIONS: Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. RESULTS: Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. CONCLUSION: Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population.

Hypersensitivity reactions due to black henna tattoos and their components: are the clinical pictures related to the immune pathomechanism?

Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by temporary black henna tattoos has become a serious health problem worldwide. Different patterns of sensitization with various clinical aspects are described in literature due to PPD associated to henna tattoo and these manifestations are likely correlated with the immunological and dermatological pathomechanisms involved. Henna is the Persian name of the plant Lawsonia inermis, Fam. Lythraceae. It is a woody shrub that grow in regions of North Africa, South Asia, India and Sri Lanka. Nowadays it is rather frequent to see temporary "tattoos" performed with henna. To make tattoos darker and long-lasting PPD has been associated to henna in tattoo drawings mixtures, so obtaining "black henna". In these years there has been a rise of contact sensitization to PPD and in medical literature an increased number of cases have been reported on temporary henna tattoo application. Here we review the various clinical patterns related to PPD and henna tattoo, to investigate the possible link between clinic-morphological pictures and the immunological response to PPD and henna. The literature underlines that different clinical manifestations are related to black henna containing PPD, and its derivative products may cause delayed-type as well as immediate-type reactions. Further studies are needed to investigate the relationship between clinical and morphological aspects of PPD contact dermatitis and the T cell subsets predominance.

Comparable Survival of En Bloc versus Standard Donor Kidney Transplants in Children.

OBJECTIVE: To determine whether renal transplantation survival is similar in children receiving pediatric en bloc kidneys compared with those receiving standard deceased donor kidneys. STUDY DESIGN: We compared time to allograft failure and estimated glomerular filtration rate (eGFR) in pediatric recipients of en bloc and standard criteria deceased donor renal transplants using Organ Procurement and Transplantation Network data for 2000-2013. Cox regression analysis was used to compare time to allograft failure, and the Student t test was used to compare eGFR. RESULTS: A total of 6882 recipients met the study inclusion criteria; 1.8% received an en bloc transplant. The adjusted hazard for allograft failure was similar for recipients of en bloc kidneys compared with standard criteria kidneys (hazard ratio, 1.15; 95% CI, 0.83-1.59; P = .41). The median wait time for transplantation was significantly shorter for recipients of en bloc kidneys (157 days vs 208 days; P = .03). Moreover, eGFR was superior for recipients of en bloc kidneys up to 5 years post-transplantation. CONCLUSION: Transplantation of en bloc pediatric kidneys should be considered a viable option for pediatric recipients and may afford unique benefits by reducing wait times and promoting preservation of graft function.

Resolution of Graves' disease after renal transplantation.

We report a case of an adolescent boy with Down's syndrome and ESRD on hemodialysis who developed mild Graves' disease that was not amenable to radioablation, surgery, or ATDs. After 14 months of observation without resolution of Graves' disease, he successfully received a DDRT with a steroid minimization protocol. Thymoglobulin and a three-day course of steroids were used for induction and he was started on tacrolimus, MMF, and pravastatin for maintenance transplant immunosuppression. One month after transplantation, all biochemical markers and antibody profiling for Graves' disease had resolved and remain normal one yr later.

Sevelamer crystals in the mucosa of the gastrointestinal tract in a teenager with end-stage renal disease.

BACKGROUND: Non-calcium-containing phosphate binders, such as sevelamer preparations, are being increasingly used in patients on dialysis due to their lower association with hypercalcemia and cardiovascular morbidity and mortality. While minor gastrointestinal side effects are quite common with the use of sevelamer, more serious gastrointestinal toxicities have only rarely been reported. CASE-DIAGNOSIS/TREATMENT: We report a pediatric patient on maintenance dialysis receiving sevelamer hydrochloride who developed severe abdominal pain and a high-grade stricture of the sigmoid colon. The patient underwent exploratory laparotomy, resulting in a partial colectomy and colostomy. Histopathologic examination showed colonic mucosal injury and characteristic "fish-scale"-like sevelamer hydrochloride crystals within the mucosa. CONCLUSIONS: Whether the sevelamer crystals were causal, contributory or purely incidental remains to be clearly elucidated. However, our case raises sufficient concern to warrant additional investigation into whether there is a causal relationship between sevelamer use and intestinal mucosal injury.

End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined.