The first randomized controlled trial in pediatric nephrology: the history of the International Study of Kidney Disease in Children (ISKDC).

The International Study of Kidney Disease in Children (ISKDC), begun in 1966, conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology and one of the first in either pediatrics or nephrology. For this trial, the ISKDC developed the criteria, such as those for response and relapse, used today to describe the clinical course of the nephrotic syndrome, and the trial generated the nephropathologic terminology and criteria which largely remain the current standards. Over an approximately 20-year span, the ISKDC followed the natural history and evaluated the therapeutic effectiveness of therapies in over 500 children with the nephrotic syndrome from three continents. It published 14 peer-reviewed studies and several reports and commentaries, many of which helped create current standards of practice for therapy of childhood nephrotic syndrome and consequently remain highly cited today. The ISKDC continues to be an important model for subsequent collaborative studies and was the impetus for the development of regional and national pediatric nephrology societies leading to the recognition and growth of pediatric nephrology as a separate subspecialty. A higher resolution version of the Graphical abstract is available as Supplementary information.

What Urinary Colony Count Indicates a Urinary Tract Infection in Children?

Post-hoc analysis of the Randomized Intervention for Children with Vesicoureteral Reflux study suggests that, in concordance with European guidelines, using bacteriologic criterion of ≥10 000 colony forming units/mL of a single organism does not decrease diagnostic specificity of an urinary tract infection in children aged 2 months to 6 years in a properly collected urine if symptoms/fever and pyuria are present. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00405704.

Sequential renal and bone marrow transplants in a child with Fanconi anemia.

FA is an autosomal recessive disorder characterized by small stature and renal abnormalities. FA can lead to progressive bone marrow failure, myelodysplastic syndrome, or acute leukemia. Using a multidisciplinary team approach, we managed a 3-yr-old boy with FA who simultaneously developed renal and hematopoietic failure. Because renal function was insufficient to support the conditioning regimen for HCT, we performed a deceased donor renal transplant in December 2012 prior to HCT with the known risk of graft-versus-graft rejection of the donor kidney. Seven months later he underwent allogeneic HCT. He obtained myeloid engraftment on day +11 and peripheral blood chimerism demonstrated all donor by day +21. He developed asymptomatic CMV reactivation and despite antirejection medications, mild skin graft-versus-host disease. He has maintained excellent renal function and remains transfusion independent with full hematopoietic recovery. He has not experienced any renal rejection episodes nor developed donor-specific antibodies toward his renal donor. Peripheral blood chimerism remains completely HCT donor. He is clinically well, now greater than two and a half yr after renal transplant and two yr after HCT. The continuing close collaboration between the Pediatric Nephrology and Bone Marrow Transplant teams is a major factor in this successful outcome.

The global pediatric nephrology workforce: a survey of the International Pediatric Nephrology Association.

BACKGROUND: The global pediatric nephrology workforce is poorly characterized. The objectives of our study were to assess pediatric nephrologists' perceptions of the adequacy of the pediatric nephrology workforce, and understand regional challenges to fellow recruitment and job acquisition. Perceptions regarding optimal length of training and research requirements were also queried. METHODS: A 17-question web-based survey comprised of 14 close-ended and 3 open-ended questions was e-mailed to members of the International Pediatric Nephrology Association. Quantitative and qualitative analyses were performed. RESULTS: We received 341 responses from members of the International Pediatric Nephrology Association from 71 countries. There was a high degree of overall perceived workforce inadequacy with 67 % of all respondents reporting some degree of shortage. Perceived workforce shortage ranged from 20 % in Australia/New Zealand to 100 % in Africa. Respondents from Africa (25 %) and North America (22.4 %) reported the greatest difficulty recruiting fellows. Respondents from Australia/New Zealand (53.3 %) and Latin America (31.3 %) reported the greatest perceived difficulty finding jobs as pediatric nephrologists after training. Low trainee interest, low salary, lack of government or institutional support, and few available jobs in pediatric nephrology were the most frequently reported obstacles to fellow recruitment and job availability. CONCLUSIONS: Globally, there is a high level of perceived inadequacy in the pediatric nephrology workforce. Regional variability exists in perceived workforce adequacy, ease of recruitment, and job acquisition. Interventions to improve recruitment targeted to specific regional barriers are suggested.

Utility of sedation for young children undergoing dimercaptosuccinic acid renal scans.

BACKGROUND: No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort. OBJECTIVE: To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort. MATERIALS AND METHODS: We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used >90% of the time (sedation centers), centers in which sedation was used <10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers). RESULTS: Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P<0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P<0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use. CONCLUSION: Selective use of sedation in children 12-36 months of age can reduce the discomfort level experienced during a DMSA scan.

The US pediatric nephrology workforce: a report commissioned by the American Academy of Pediatrics.

The US pediatric nephrology workforce is poorly characterized. This report describes clinical and nonclinical activities, motivations and disincentives to a career in pediatric nephrology, future workforce needs, trainee recruitment, and possible explanations for personnel shortages. An e-mail survey was sent in 2013 to all identified US-trained or -practicing pediatric nephrologists. Of 504 respondents, 51% are men, 66% are US graduates, and 73% work in an academic setting. About 20% of trained pediatric nephrologists no longer practice pediatric nephrology. Among the 384 respondents practicing pediatric nephrology full or part-time in the United States, the mean work week was 56.1±14.3 hours, with time divided between patient care (59%), administration (13%), teaching (10%), clinical research (9%), basic research (6%), and other medical activities (3%). Most (>85%) care for dialysis and transplantation patients. The median number of weeks annually on call is 16, and 29% work with one or no partner. One-third of US pediatric nephrologists (n=126) plan to reduce or stop clinical nephrology practice in the next 5 years, and 53% plan to fully or partially retire. Almost half the division chiefs (47%) report inadequate physician staffing. Ongoing efforts to monitor and address pediatric nephrology workforce issues are needed.

Wanted: pediatric nephrologists! - why trainees are not choosing pediatric nephrology.

A workforce crisis for many pediatric specialties, particularly nephrology, is due to growing retirement rates, attrition during training, and retention difficulties. To obtain specific information regarding pediatric nephrology trainee shortages, we administered two cross-sectional surveys to non-renal pediatric subspecialty fellows and pediatric nephrology program directors. We characterized the fellows' experiences with nephrology and the program directors' experiences with their fellows as well as their outcomes in the last 10 years. We analyzed responses from 531 non-renal fellows (14.4% response rate). Overall, 317 (60%) fellows rated nephrology as difficult, particularly women (65.4% vs. 49.5%, p < 0.001), with American women medical graduates rating nephrology as more difficult compared to all others (p = 0.001). More men than women (24% vs. 8%, p < 0.001) considered the monetary benefit as not adequate. Program directors (25; 64% response rate) represented 57% of all USA fellows in training, and 15 (60%) found it difficult to recruit qualified applicants. Of the 183 graduates in the past 10 years, 35 (19%) were reported as not in the USA pediatric nephrology workforce. These findings support our belief that a strong effort needs to be made by the academic community to teach nephrology in more interesting and understandable formats. While these are national samples, we were unable to contact non-nephrology fellows directly and program directors from larger programs were underrepresented. Difficulties in attracting/retaining trainees (particularly women) to nephrology must be addressed systematically, identifying incentives to practice in this field. Bold concerted efforts are required and we propose seven steps to achieve this goal.

Cognitive pharmacy services at a pediatric nephrology and hypertension clinic.

PURPOSE: Pediatric patients require special attention from pediatric pharmacists. This is particularly true for pediatric patients with chronic kidney disease (CKD) as the number of their medications and the complexity of their treatment increase with disease progression. However, there is paucity of information describing pediatric cognitive pharmacy services in this setting. The objective of this study is to identify the potential roles of a clinical pharmacist as a provider in a pediatric nephrology and hypertension clinic. METHODS: Pediatric patients (≤18 years of age) who chronically took at least one medication were consecutively enrolled at the University of North Carolina (UNC) Pediatric Nephrology and Hypertension Clinic from 1 August 2007 to 15 April 2008. Demographic information and the interventions performed during the clinic visit by a clinical pharmacist were examined. RESULTS: Three hundred and seventy-four visits made in 283 participants were evaluated. The mean (SD) number of cognitive pharmacy interventions per patient was 2.3 (1.0) on the first visit, with medication counseling and verification of current medications comprising the most common activity (85%). The mean (SD) number of medications per patient was 5.7 (4.8) and of medications counseled per visit was 4.0 (3.4). Medication adherence was investigated in 141 (38%) visits. Pretransplant education on medications was performed in 3% of the patients. Discrepancies of medications were discovered in 12 of the 374 visits. CONCLUSION: Pediatric cognitive pharmacy services to patients at the UNC pediatric nephrology clinic were feasible, which improved the quality of services and promoted better outcomes for these complex patients.

Are My Pediatric Patients at Increased Risk of Developing Chronic Kidney Disease?

Chronic kidney disease (CKD) is an underrecognized and often undiagnosed cause of morbidity and mortality. Many children and adolescents are at increased risk of developing CKD as they mature and age, secondary to conditions commonly cared for by pediatric health professionals. Prematurity, diabetes mellitus, hypertension, congenital heart disease, sickle cell disease and trait, severe obesity, cancer chemotherapy, other drug toxicities, and systemic situations that may cause acute kidney injury such as sepsis or extracorporeal membrane oxygenation therapy predispose to potential CKD. Clinicians should be aware of these conditions in order to screen for CKD, choose non-nephrotoxic treatments for these children whenever possible, and treat or refer those who have early signs of CKD.

Cryoglobulinemia and glomerular rhomboid inclusions in a child with acute kidney injury.

Cryoglobulinemia is rarely reported in children, and kidney failure secondary to cryoglobulinemia is even more uncommon. We report the case of a 7-year-old boy with cryoglobulins and a systemic illness, including persistent fever, arthralgias, rash, hypocomplementemia, and acute kidney injury associated with nephritic urine sediment. An extensive workup showed no infectious, neoplastic, or rheumatological cause of his kidney injury. The kidney biopsy specimen showed membranoproliferative glomerulonephritis type 1 with electron microscopic evidence of rhomboid crystalloid inclusions. These inclusions have rarely been reported in adult patients with cryoglobulinemia. The patient underwent spontaneous remission, including full recovery of kidney function, and required no immune suppression. The patient's course is consistent with cryoglobulinemia-associated kidney injury, which supports the inclusion of essential cryoglobulinemia in the differential diagnosis of pediatric patients with hypocomplementemic glomerulonephritis.

Primary varicella after transplantation.

A 51-year-old white woman 6 months status post cadaveric renal transplant developed a mild case of primary varicella-zoster (VZ). It is hypothesized that the limited nature of her illness was due to infection with vaccine-type VZ virus instead of wild-type VZ. Approximately 1 month prior, she had daily household contact with a child who had developed a rash after immunization with live attenuated varicella vaccine. This case highlights several important questions. Should special precautions be undertaken with renal transplant recipients naive to varicella infection after vaccination of household contacts? Should pretransplant immunization with varicella vaccine be performed routinely in naive patients? Should naive patients transplanted and maintained on immunosuppressive therapy be vaccinated? Until there are clinical trials to answer these questions, it may be instructive to consider the recommendations for pediatric and immunocompromised patients.

Generalist-subspecialist communication about children with chronic conditions: an analysis of physician focus groups.

OBJECTIVE: To describe barriers and facilitators to effective generalist-subspecialist communication in the care of children with chronic conditions. METHODS: We conducted 5 focus groups with 14 general pediatricians and 10 pediatric specialty providers to discuss factors that facilitate or obstruct effective communication. The specialty groups included 2 nurse practitioners; the rest were pediatricians from an academic medical center and the surrounding community. We performed a content analysis to generate groups of themes and classify them as barriers or facilitators, and we returned to the participants to solicit their feedback. RESULTS: We identified 201 themes in 6 domains: the method, content, and timing of communication; system factors; provider education; and interpersonal issues. Barriers to communication mostly involved the method of communication and system factors. Most facilitating themes promoted timely communication, understanding of the reasons for referral and the nature of the child's condition, or appropriate definition of generalist and specialist roles. Participants described numerous examples where communication had direct effects on patient outcomes. Generalists and specialists agreed on many issues, although specialists discussed the pros and cons of curbside consults at length whereas generalists emphasized the importance of their own education in the referral-consultation process. CONCLUSIONS: Efforts to improve communication between pediatric generalists and specialists in the care of children with chronic conditions should emphasize the importance of timely information transfer. The content of messages is important, but lack of receipt when needed is more of a problem. Improving generalist-subspecialist communication has great potential to improve the quality of care.

Predictors of relapse and end stage kidney disease in proliferative lupus nephritis: focus on children, adolescents, and young adults.

BACKGROUND AND OBJECTIVES: The prevalence and significance of remission and relapse in children, adolescents, and young adults with lupus nephritis in the United States are poorly understood. Patterns and predictors of disease progression in a southeastern U.S. pediatric cohort with severe lupus nephritis are presented. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Individuals age 21 or less with kidney biopsy-proven lupus nephritis followed in the Glomerular Disease Collaborative Network were included. Cox regression models were used to evaluate predictors of relapse and end stage kidney disease (ESKD). RESULTS: Seventy-three subjects with a mean age of 15.6 +/- 3.4 yr were included. Five-year kidney survival was 77%. Complete and partial remission rates within 1 yr of induction therapy were 25 and 64%, respectively. Relapse and ESKD rates were similar between complete and partial responders. Relapse occurred in 35% of responders (complete or partial) in 45 +/- 32 mo. Disease relapse was a predictor of ESKD (HR = 10.12, P < 0.0001). Treatment resistance was documented in African Americans more often than non-African Americans (eight versus 0; P = 0.03). ESKD HR associated with treatment resistance was 6.25, P < 0.002. CONCLUSIONS: Remission whether complete or partial is associated with improved kidney survival in children with lupus nephritis. Nephritis relapse is a strong predictor of progression to ESKD. Treatment resistance portends a high risk of ESKD and disproportionately affects African American children with lupus nephritis.

Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study.

OBJECTIVE: Our goal is to determine if antimicrobial prophylaxis with trimethoprim/sulfamethoxazole prevents recurrent urinary tract infections and renal scarring in children who are found to have vesicoureteral reflux after a first or second urinary tract infection. DESIGN, PARTICIPANTS, AND METHODS: The Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study is a double-blind, randomized, placebo-controlled trial. Six hundred children aged 2 to 72 months will be recruited from both primary and subspecialty care settings at clinical trial centers throughout North America. Children who are found to have grades I to IV vesicoureteral reflux after the index febrile or symptomatic urinary tract infection will be randomly assigned to receive daily doses of either trimethoprim/sulfamethoxazole or placebo for 2 years. Scheduled follow-up contacts include in-person study visits every 6 months and telephone interviews every 2 months. Biospecimens (urine and blood) and genetic specimens (blood) will be collected for future studies of the genetic and biochemical determinants of vesicoureteral reflux, recurrent urinary tract infection, renal insufficiency, and renal scarring. RESULTS: The primary outcome is recurrence of urinary tract infection. Secondary outcomes include time to recurrent urinary tract infection, renal scarring (assessed by dimercaptosuccinic acid scan), treatment failure, renal function, resource utilization, and development of antimicrobial resistance in stool flora. CONCLUSIONS: The RIVUR study will provide useful information to clinicians about the risks and benefits of prophylactic antibiotics for children who are diagnosed with vesicoureteral reflux after a first or second urinary tract infection. The data and specimens collected over the course of the study will allow researchers to better understand the pathophysiology of recurrent urinary tract infection and its sequelae.

Parents as information intermediaries between primary care and specialty physicians.

OBJECTIVE: In this study we assessed the views of parents of children referred to specialty care and the views of the children's primary care and specialty physicians about parents' roles as information intermediaries. METHODS: We enrolled 179 patients who were newly referred from primary care pediatricians in 22 practices to 15 pediatric subspecialists in 5 specialties in a study of primary care pediatrician-specialist communication. Parents, primary care pediatricians, and specialists completed questionnaires by mail or telephone at the first visit and 6 months later. Questions included perceived responsibilities of parents as information conduits between primary care pediatricians and specialists. Opinions of parents, primary care pediatricians, and specialists about parents' roles were compared for the sample as a whole, as well as for individual cases. Agreement between parents and providers was assessed. Demographic and clinical determinants of parents reporting themselves as "comfortable with" or "acting" as primary intermediaries were assessed using logistic regression. RESULTS: More parents (44%) than primary care physicians (30%) felt comfortable with parents acting as primary communicators between their children's physicians; 31% of parents who reported that they were the primary communicators felt uncomfortable in that role, and there was no agreement between parents and physicians about the role of parents in individual cases. Although no demographic characteristics of children or parents were associated with parent comfort as the primary communicator, parents of children who saw the same specialist more than once during the 6-month period felt more comfortable in this role. The presence of a chronic condition was not associated with parent comfort. CONCLUSIONS: Although parents report more comfort with their own ability as information intermediaries than do their children's physicians, the role in which they feel comfortable is highly variable. Physicians should discuss with parents the roles they feel comfortable in assuming when specialty referrals are initiated.