Diagnosis and management of primary hyperoxalurias: best practices.

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment.

Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

A novel MBTPS2 variant associated with BRESHECK syndrome impairs sterol-regulated transcription and the endoplasmic reticulum stress response.

Ichthyosis follicularis, atrichia, and photophobia syndrome (IFAP syndrome) is a rare, X-linked disorder caused by pathogenic variants in membrane-bound transcription factor protease, site 2 (MBTPS2). Pathogenic MBTPS2 variants also cause BRESHECK syndrome, characterized by the IFAP triad plus intellectual disability and multiple congenital anomalies. Here we present a patient with ichthyosis, sparse hair, pulmonic stenosis, kidney dysplasia, hypospadias, growth failure, thrombocytopenia, anemia, bone marrow fibrosis, and chronic diarrhea found by research-based exome sequencing to harbor a novel, maternally inherited MBTPS2 missense variant (c.766 G>A; (p.Val256Leu)). In vitro modeling supports variant pathogenicity, with impaired cell growth in cholesterol-depleted media, attenuated activation of the sterol regulatory element-binding protein pathway, and failure to activate the endoplasmic reticulum stress response pathway. Our case expands both the genetic and phenotypic spectrum of BRESHECK syndrome to include a novel MBTPS2 variant and cytopenias, bone marrow fibrosis, and chronic diarrhea.

Long-term outcome among females with Alport syndrome from a single pediatric center.

BACKGROUND: Alport syndrome (AS) is a multisystem condition which can result in progressive kidney disease, hearing loss, and ocular changes. X-linked inheritance is observed in 85% of affected individuals. As a result, most prior studies have focused on males. Girls with AS can also be symptomatic although historically thought to have few clinical manifestations in childhood. The objective of the study was to describe the clinical presentation and course of females with AS. METHODS: A single-center retrospective study of all young females with AS between January 1, 1987, and May 20, 2019. Subjects were identified using ICD-9/10 diagnosis codes for AS, familial hematuria, or nephritis. Clinical data were extracted by retrospective chart review. RESULTS: Thirty-six female patients were included in the analysis. Mean age at presentation was 5.58 ± 3.0 years, and mean follow-up was 5.9 ± 3.9 years. Twenty-nine patients (80%) had a family history of AS. At end of the follow-up period, gross hematuria was observed in 15 patients (42%), 20 (56%) developed proteinuria, and 2 (6.7%) had an estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 with one patient developing stage 5 chronic kidney disease. Four of the twenty-seven (14.8%) who underwent audiologic testing had an abnormal exam. CONCLUSIONS: Known family histories of AS or gross hematuria were the most common reasons for the initial presentation in our cohort. Development of proteinuria, eGFR < 90 ml/min/1.73m2, and abnormal audiology exam are not exceptional findings, suggesting that close monitoring of young females into adulthood is warranted.

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.

Inflammatory Bowel Diseases Are Associated With an Increased Risk for Chronic Kidney Disease, Which Decreases With Age.

BACKGROUND & AIMS: It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR). METHODS: We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n = 17,807) were matched for age, sex, and practice to individuals without IBD (n = 63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model. RESULTS: After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16-77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56-24.19) at age 16 to 1.13 (95% CI, 1.01-1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m2; 95% CI, 0.16-0.48). CONCLUSIONS: In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.

Prevention of recurrent urinary stone disease.

PURPOSE OF REVIEW: Urinary stone disease (USD) is increasing in prevalence and recurrence is common. In pediatrics, most stones are composed primarily of calcium with the highest incidence observed in adolescents. Given the morbidity associated with USD, an in depth review of current management strategies is of paramount importance to highlight the data supporting the recommended treatments and the knowledge gaps which still exist. RECENT FINDINGS: Several interventions for the management of recurrent calcium USD in children have been recommended based on primarily adult studies. These interventions include modification of diet and fluid intake in addition to the utilization of medications such as thiazide diuretics and citrates when supportive care is inadequate. Overall there is conflicting data in the adult literature which is further complicated by our attempts to extrapolate these data to children. SUMMARY: Based on the currently available literature the management of USD in pediatrics should be individualized to each patient and focused on the particular metabolic risk factors that are identified during the course of their evaluation. Several interventions may be required or trialed in a particular patient to show an effect. Well designed trials to assess the efficacy of each intervention in the pediatric population are needed.

New insights into the pathogenesis of Streptococcus pneumoniae-associated hemolytic uremic syndrome.

The purpose of this review is to describe Streptococcus pneumoniae-associated hemolytic uremic syndrome (P-HUS) with emphasis on new insights into the pathophysiology and management over the past 10 years. Even though awareness of this clinico-pathological entity has increased, it likely remains under-recognized. Recent observations indicate that although neuraminidase activity and exposure of the T-antigen are necessary for development of P-HUS, they are not sufficient; activation of the alternate pathway of complement may also contribute. It is unclear, however, whether or not eculizumab and/or plasmapheresis are of value.

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.

Oral Antibiotic Exposure and Kidney Stone Disease.

Background Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown.Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case-control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins.Results Exposure to any of five different antibiotic classes 3-12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3-6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3-5 years from exposure.Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.

Salt, sweat, and unclear? Diaphoresis and hypernatremia in end-stage kidney disease: Questions.

This quiz will discuss two patients with end-stage kidney disease (ESKD) on dialysis presenting with diaphoresis and hypernatremia.

Dietary Zinc and Incident Calcium Kidney Stones in Adolescence.

PURPOSE: We determined the association between dietary zinc intake and incident calcium kidney stones in adolescents. We also examined the relationship between dietary zinc intake and urinary zinc excretion between cases and controls. MATERIALS AND METHODS: We conducted a nested case-control study within a large pediatric health care system. Three 24-hour dietary recalls and spot urine chemistry analyses were obtained for 30 participants 12 to 18 years old with a first idiopathic calcium based kidney stone and 30 healthy controls matched for age, sex, race and month of enrollment. Conditional logistic regression models were used to estimate the association between daily zinc intake and incident calcium kidney stones, adjusting for dietary phytate, protein, calcium, sodium and oxalate. Multivariable linear regression was used to estimate the association between dietary and urine zinc, adjusting for urine creatinine and dietary phytate and calcium. RESULTS: Cases had lower daily zinc intake (8.1 mg) than controls (10 mg, p = 0.029). Daily zinc intake of boys and girls with calcium stones was 2 mg and 1.2 mg less, respectively, than the daily intake recommended by the Institute of Medicine. Odds of incident stones were reduced by 13% for every 1 mg increase in daily zinc intake (OR 0.87, 95% CI 0.75-0.99). There was an estimated 4.5 µg/dl increase in urine zinc for every 1 mg increase in dietary zinc (p = 0.009), with weak evidence of a smaller increase in urine zinc in cases than in controls (interaction p = 0.08). CONCLUSIONS: Decreased dietary zinc intake was independently associated with incident calcium nephrolithiasis in this population of adolescents.

Variability in measures of mineral metabolism in children on hemodialysis: impact on clinical decision-making.

BACKGROUND: Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making. METHODS: We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study. RESULTS: The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH. CONCLUSIONS: There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.

Risk of Urolithiasis in Anorexia Nervosa: A Population-Based Cohort Study Using the Health Improvement Network.

This population-based retrospective cohort study sought to determine if anorexia nervosa (AN) is associated with a higher risk of urolithiasis. Nine thousand three hundred two females with AN were compared to 92 959 randomly selected age-matched and practice-matched females. Cox regression was used to estimate the hazard ratio (HR) for urolithiasis and evaluate effect modification by age. Twenty-three participants with AN (0.25%) developed urolithiasis compared with 154 unexposed participants (0.17%) over a median of 4 years of observation. The risk of urolithiasis varied significantly with age (interaction p = 0.02). AN was associated with a more than threefold higher risk of urolithiasis in females ≤25 years of age (HR 3.49, 95% CI: 1.56-7.81; p = 0.002), but not in females over 25 years (HR 1.18, 95% CI: 0.69-2.02; p = 0.54). The distribution of diagnosis codes for urolithiasis differed between groups (p = 0.04), with a higher proportion of codes for uric acid urolithiasis in the AN (16.2%) versus unexposed group (5.0%). Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Assessing the risk of incident hypertension and chronic kidney disease after exposure to shock wave lithotripsy and ureteroscopy.

In this study we sought to determine if among individuals with urolithiasis, extracorporeal shock wave lithotripsy (SWL) and ureteroscopy are associated with a higher risk of incident arterial hypertension (HTN) and/or chronic kidney disease (CKD). This was measured in a population-based retrospective study of 11,570 participants with incident urolithiasis and 127,464 without urolithiasis in The Health Improvement Network. Patients with pre-existing HTN and CKD were excluded. The study included 1319 and 919 urolithiasis patients with at least one SWL or URS procedure, respectively. Multivariable Cox regression was used to estimate the hazard ratio for incident CKD stage 3-5 and HTN in separate analyses. Over a median of 3.7 and 4.1 years, 1423 and 595 of urolithiasis participants developed HTN and CKD, respectively. Urolithiasis was associated with a significant hazard ratio each for HTN of 1.42 (95% CI: 1.35, 1.51) and for CKD of 1.82 (1.67, 1.98). SWL was associated with a significant increased risk of HTN 1.34 (1.15, 1.57), while ureteroscopy was not. When further stratified as SWL to the kidney or ureter, only SWL to the kidney was significantly and independently associated with HTN 1.40 (1.19, 1.66). Neither SWL nor ureteroscopy was associated with incident CKD. Since urolithiasis itself was associated with a hazard ratio of 1.42 for HTN, an individual who undergoes SWL to the kidney can be expected to have a significantly increased hazard ratio for HTN of 1.96 (1.67, 2.29) compared with an individual without urolithiasis.

Evaluation and medical management of kidney stones in children.

PURPOSE: We review the current literature on the diagnostic evaluation and dietary and pharmacological management of children with nephrolithiasis. MATERIALS AND METHODS: We searched MEDLINE(®), Embase(®) and the Cochrane Library from their inceptions to March 2014 for published articles in English on kidney stones and therapy in children 0 to 18 years old. Based on review of the titles and abstracts, 110 of the 1,014 articles (11%) were potentially relevant to the diagnostic evaluation and medical management of nephrolithiasis in children. We summarized this literature and drew on studies performed in adult populations to augment areas in which no studies of sufficient quality have been performed in children, and to highlight areas in need of research. RESULTS: During the last 25 years the incidence of nephrolithiasis in children has increased by approximately 6% to 10% annually and is now 50 per 100,000 adolescents. Kidney stones that form during childhood have a similar composition to those that form in adulthood. Approximately 75% to 80% of stones are composed of predominantly calcium oxalate, 5% to 10% are predominantly calcium phosphate, 10% to 20% are struvite and 5% are pure uric acid. The recurrence rate of nephrolithiasis in patients with stones that form during childhood is poorly defined. Ultrasound should be used as the initial imaging study to evaluate children with suspected nephrolithiasis, with noncontrast computerized tomography reserved for those in whom ultrasound is nondiagnostic and the suspicion of nephrolithiasis remains high. Current treatment strategies for children with kidney stone disease are based largely on extrapolation of studies performed in adult stone formers and single institution cohort or case series studies of children. Tamsulosin likely increases the spontaneous passage of ureteral stones in children. Increased water intake and reduction of salt consumption should be recommended for all children with a history of kidney stones. Potassium citrate is a potentially effective medication for children with calcium oxalate stones and concomitant hypocitraturia, as well as children with uric acid stones. However, long-term compliance with therapy and the effect on decreasing stone recurrence in children are unknown. Based largely on efficacy in adult populations, thiazide diuretics should be considered in the treatment of children with calcium based stones and persistent hypercalciuria refractory to reductions in salt intake. CONCLUSIONS: The incidence of kidney stone disease in children is increasing, yet few randomized clinical trials or high quality observational studies have assessed whether dietary or pharmacological interventions decrease the recurrence of kidney stones in children. Collaborative efforts and randomized clinical trials are needed to determine the efficacy and effectiveness of alternative treatments for children with nephrolithiasis, particularly those with calcium oxalate stones and concomitant hypercalciuria and hypocitraturia. Additional areas in need of study are the optimal length of time for a trial of stone passage in children, the cost-effectiveness of medical expulsive therapy vs analgesics alone, and the size and location of stones for which medical expulsive therapy is most effective.

Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric malignancy: case series and review of the literature.

BACKGROUND: Tyrosine kinase (TK) inhibitors are increasingly being used to treat a variety of pediatric malignancies. Reports in adult patients describe a range of effects of TK inhibitors on the kidney, including hypertension, proteinuria, acute kidney injury, and thrombotic microangiopathy (TMA); however, there are only a few reports of TK-inhibitor-associated nephrotic syndrome. METHODS: We report four pediatric patients with various malignancies (chronic myelogenous leukemia, acute lymphoblastic leukemia, and glioma/renal cell carcinoma) who developed nephrotic syndrome during treatment with TK inhibitors (imatinib, sunitinib, dasatinib, and quizartinib). One of the four patients also had clinical features of TMA. RESULTS: Three of the four patients achieved complete remission of nephrotic syndrome with discontinuation of the TK inhibitor and have had no additional nephrotic syndrome relapses to date. The temporal relationship of nephrotic syndrome onset to TK-inhibitor therapy and resolution of nephrotic syndrome with cessation of therapy strongly imply an association in these patients. CONCLUSIONS: TK inhibitors are important therapies in pediatric cancer, and their use is expanding. Nephrotic syndrome with or without features of TMA is a potential complication of these therapies in children.