William A. Primack

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.

Anaphylaxis to Cutaneous Exposure to Milk Protein in a Diaper Rash Ointment

A 12-month-old boy, with a strong history of cows milk allergy, developed two episodes of anaphylaxis following cutaneous application of a casein containing ointment to an inflamed diaper area. RAST testing showed a significant elevation in specific IgE antibodies to milk and milk proteins. This experience suggests that children who are highly sensitive to milk may have severe allergic reactions on cutaneous exposure to milk or milk products.

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 childs 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.

Aggressive respiratory support and unilateral nephrectomy for infants with severe perinatal autosomal recessive polycystic kidney disease.

Newborn infants with severe autosomal recessive polycystic kidney disease often receive minimal intervention because poor respiratory and renal outcomes are anticipated. We describe two patients whose respiratory failure was successfully treated with aggressive intervention. Massive kidneys restricted gastrointestinal capacity and limited feedings. Uninephrectomy allowed adequate enteral feedings and preserved sufficient renal function for homeostasis and growth.

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.

Corticosteroid Therapy for Henoch Schönlein Purpura

Weiss et al’s1 meta-analysis concludes that several weeks of corticosteroid use decreases the risk of longterm renal disease in children presenting with Henoch Schonlein purpura (HSP). They base this conclusion on a combined odds ratio ([OR]: 0.43; 95% confidence interval (CI): [0.19 – 0.96]) of 3 placebo-controlled or prospective trials. We disagree with their conclusion on the basis of selection bias in the studies reported, differences in duration of follow-up, as well as new data from a prospective study presented by Dudley et al2 at the 2007 American Society of Nephrology meeting that reported no differences in development of renal disease between those receiving prednisolone and placebo (OR: 1.32; 95% CI: [0.59 –2.94]). Extrapolating the results of the analyzed trials to the practice of the primary care pediatrician may not be wise, because the children reported were either hospitalized for HSP or presented to a tertiary care level emergency department. It is reasonable to assume that they, on average, were sicker and may have had more severe involvement than the child with HSP presenting to a primary care practice. Methodologic issues that raise concern about the validity of Weiss et al’s1 meta-analysis include differences in treatment regimens and follow-up duration. Follow-up periods for each study were quite different with Ronkainen et al3 who reported 6 months of follow-up compared with 1 year for the Mollica et al4 and Huber et al5 trials. Also, the Mollica et al4 study, which was designed as an incidence trial compared with the prevalence design of the other 3 studies, included 2 patients who developed renal disease 1 year after their HSP diagnosis but are not taken into account by Weiss et al1 in their metanalysis. If we exclude Mollica et al4 from the meta-analysis and add the Dudley et al2 study, we measure a new combined OR: 0.89; 95% CI (0.52–1.54). However, if the Dudley et al and Mollica et al2,4 studies are included, we measure a combined OR: 0.77; 95% CI (0.44 –1.39) (Fig 1). Both of the combined OR reported indicate a trend toward supporting steroids in patients with HSP, but neither are statistically significant because the CIs cross the null. Weiss et al1 in their sensitivity analysis for future studies estimate that 5%–20% of untreated patients with HSP will develop persistent renal involvement. This is a large overestimate because long-term studies of unselected patients with HSP show less than a 2% prevalence of persistent renal involvement.6 The relatively small subgroup of HSP patients who may benefit from corticosteroids includes those who present with renal involvement and probably those with severe abdominal symptoms requiring medical attention.4,6,7 In summary, we feel the data does not currently exist, however, to recommend the routine use of corticosteroids to prevent renal disease in children with uncomplicated HSP, and that if steroids are to be used for these children, it should be only in the context of a controlled trial.

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.

An Analysis of the Approach to Management of Childhood Nephrotic Syndrome by Pediatric Nephrologists

The value of a renal biopsy for a child with frequently relapsing corticosteroid-responsive or corticosteroid-dependent nephrotic syndrome is unresolved. This was the subject of two independent surveys done by North American pediatric nephrologists. In one study, 59% of the respondents indicated that they would nearly always perform a biopsy prior to starting cytotoxic therapy, while 23% would do so rarely. Less experienced pediatric nephrologists were more inclined to recommend a biopsy (P < 0.05). The indications for a renal biopsy were to provide prognostic information and to make decisions concerning further therapy. In the second survey, 33% of pediatric nephrologists said they would perform a renal biopsy in children with frequent relapses, while 91% would recommend a biopsy in children with corticosteroid resistance (P < 0.001). Once a biopsy was performed, therapy was based on the histopathologic findings regardless of the previous clinical response to corticosteroids. At this time, there is no standard approach to the evaluation and management of children with frequently relapsing, corticosteroid-dependent nephrotic syndrome. Some physicians rely on their clinical acumen, whereas others depend on the histopathologic findings.

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 patients 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.

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.